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Sample records for nonphysiological immunoglobulin variable

  1. Immunoglobulin G concentration in canine colostrum: Evaluation and variability.

    PubMed

    Mila, Hanna; Feugier, Alexandre; Grellet, Aurélien; Anne, Jennifer; Gonnier, Milène; Martin, Maelys; Rossig, Lisa; Chastant-Maillard, Sylvie

    2015-11-01

    Canine neonates are born hypogammaglobulinemic, and colostrum is their main source of immunoglobulins. The purpose of this study was to evaluate the immune quality of canine colostrum and its variability both among bitches and among mammary glands. The immune quality was estimated from immunoglobulin G (IgG) concentration (ELISA test). The correlation of IgG concentration with refractometry was evaluated. From a total of 44 bitches from 13 different breeds from a single breeding kennel, samples of colostrum and blood were collected one day after the parturition onset. Colostrum was collected separately from each pair of mammary glands (180 pairs). The mean colostrum IgG concentration in our population was 20.8 ± 8.1g/L (ranging from 8.0 to 41.7 g/L) with no influence of breed size, litter size, age of dam or serum IgG concentration. Colostrum IgG concentration varied widely among pairs of mammary glands within one bitch (variation coefficient: 42 ± 32.1%). Nevertheless, no single pair of mammary glands was found to produce regularly a secretion of higher quality. No difference in IgG concentration was recorded between anterior and posterior pairs either. The BRIX index and the refractive index were significantly, but moderately correlated with colostrum IgG concentration (r=0.53 and 0.42, respectively). This study demonstrates a great variability in immune quality of colostrum among bitches and among mammary glands within one bitch. Further studies on the suckling behavior of puppies and on determination of the minimal immune quality of colostrum are required to evaluate their impact of this high variability on neonatal mortality in dogs. PMID:26186389

  2. Rapid cloning of any rearranged mouse immunoglobulin variable genes

    SciTech Connect

    Dattamajumdar, A.K.; Jacobson, D.P.; Hood, L.E.; Osman, G.E.

    1996-12-31

    Immunoglobulins (Ig) have been the focus of extensive study for several decades and have become an important research area for immunologists and molecular biologists. The use of polymerase chain reaction (PCR) technology has accelerated the cloning, sequencing, and characterization of genes of the immune system. However, cloning and sequencing the Ig variable (V) genes using the PCR technology has been a challenging task, primarily due to the very diverse nature of Ig V region genes. We have developed a simple, rapid, and reproducible PCR-based technique to clone any rearranged mouse Ig heavy or light chain genes. A close examination of all Ig heavy and light chain V gene families has resulted in the design of 5{prime} and 3{prime} universal primers from regions that are highly conserved across all heavy or light chain V gene families, and the joining or constant regions, respectively. We present our strategy for designing universal primers for Ig V gene families. These primers were able to rapidly amplify the rearranged Ig V genes, belonging to diverse Ig V gene families from very different cell lines, i.e., J558, MOPC-21, 36-60, and a chicken ovalbumin specific B-cell hybridoma. In addition, the present study provides the complete alignment of nucleotide sequences of all heavy and light chain variable gene families. This powerful method of cloning Ig V genes, therefore, allows rapid and precise analysis of B-cell hybridomas, B-cell repertoire, and B-cell ontogeny. 55 refs., 5 figs., 2 tabs.

  3. Proteomic analysis of sera from common variable immunodeficiency patients undergoing replacement intravenous immunoglobulin therapy.

    PubMed

    Spadaro, Giuseppe; D'Orio, Concetta; Genovese, Arturo; Galeotafiore, Antonella; D'Ambrosio, Chiara; Di Giovanni, Stefano; Vitale, Monica; Capasso, Mario; Lamberti, Vincenzo; Scaloni, Andrea; Marone, Gianni; Zambrano, Nicola

    2011-01-01

    Common variable immunodeficiency is the most common form of symptomatic primary antibody failure in adults and children. Replacement immunoglobulin is the standard treatment of these patients. By using a differential proteomic approach based on 2D-DIGE, we examined serum samples from normal donors and from matched, naive, and immunoglobulin-treated patients. The results highlighted regulated expression of serum proteins in naive patients. Among the identified proteins, clusterin/ApoJ serum levels were lower in naive patients, compared to normal subjects. This finding was validated in a wider collection of samples from newly enrolled patients. The establishment of a cellular system, based on a human hepatocyte cell line HuH7, allowed to ascertain a potential role in the regulation of CLU gene expression by immunoglobulins.

  4. Specific amplification by PCR of rearranged genomic variable regions of immunoglobulin genes from mouse hybridoma cells.

    PubMed

    Berdoz, J; Monath, T P; Kraehenbuhl, J P

    1995-04-01

    We have designed a novel strategy for the isolation of the rearranged genomic fragments encoding the L-VH-D-JH and L-V kappa/lambda-J kappa/lambda regions of mouse immunoglobulin genes. This strategy is based on the PCR amplification of genomic DNA from mouse hybridomas using multiple specific primers chosen in the 5'-untranslated region and in the intron downstream of the rearranged JH/J kappa/lambda sequences. Variable regions with intact coding sequences, including full-length leader peptides (L) can be obtained without previous DNA sequencing. Our strategy is based on a genomic template that produces fragments that do not need to be adapted for recombinant antibody expression, thus facilitating the generation of chimeric and isotype-switched immunoglobulins.

  5. Structure reveals function of the dual variable domain immunoglobulin (DVD-Ig™) molecule

    PubMed Central

    Jakob, Clarissa G.; Edalji, Rohinton; Judge, Russell A.; DiGiammarino, Enrico; Li, Yingchun; Gu, Jijie; Ghayur, Tariq

    2013-01-01

    Several bispecific antibody-based formats have been developed over the past 25 years in an effort to produce a new generation of immunotherapeutics that target two or more disease mechanisms simultaneously. One such format, the dual-variable domain immunoglobulin (DVD-Ig™), combines the target binding domains of two monoclonal antibodies via flexible naturally occurring linkers, which yields a tetravalent IgG - like molecule. We report the structure of an interleukin (IL)12-IL18 DVD-Ig™ Fab (DFab) fragment with IL18 bound to the inner variable domain (VD) that reveals the remarkable flexibility of the DVD-Ig™ molecule and how the DVD-Ig™ format can function to bind four antigens simultaneously. An understanding of how the inner variable domain retains function is of critical importance for designing DVD-Ig™ molecules, and for better understanding of the flexibility of immunoglobulin variable domains and linkers, which may aid in the design of improved bi- and multi-specific biologics in general. PMID:23549062

  6. SAW: a graphical user interface for the analysis of immunoglobulin variable domain sequences.

    PubMed

    Elgavish, R A; Schroeder, H W

    1993-12-01

    The Sequence Analysis Workshop (SAW) is an interactive program for sequence analysis of immunoglobulin variable domains. Sequences for SAW can be obtained from GenBank or from a standard text file. SAW can compare a variable domain to as many as 100 different sequences, calculate the extent of homology, sort the sequences by their degree of similarity, translate the nucleotide codons into amino acids and then display the results in either a graphical or text format. These comparisons allow the investigator to determine the likely germ-line progenitors of a variable domain and to visualize how it differs from other antibody genes by functional region. SAW supports replacement and silent site substitution analysis by either codon or region, thus providing rapid insight into the forces that have shaped mutations. The sequence comparisons can be printed out as an aid for paper analysis or for preparation of figures for publication. SAW is written in Microsoft C for use with the Microsoft Windows graphics environment. The use of color and graphics, the generation of subsidiary windows that contain the results of specific analyses and the mouse-driven control of the program make SAW an easy-to-use tool for immunoglobulin sequence comparison. PMID:8292340

  7. A family of variable immunoglobulin and lect in domain containing molecules in the snail Biomphalaria glabrata

    PubMed Central

    Dheilly, Nolwenn M; Duval, David; Mouahid, Gabriel; Emans, Rémi; Allienne, Jean-François; Galinier, Richard; Genthon, Clémence; Dubois, Emeric; Pasquier, Louis Du; Adema, Coen M; Grunau, Christoph; Mitta, Guillaume; Gourbal, Benjamin

    2014-01-01

    Technical limitations have hindered comprehensive studies of highly variable immune response molecules that are thought to have evolved due to pathogen-mediated selection such as Fibrinogen-related proteins (FREPs) from Biomphalaria glabrata. FREPs combine upstream immunoglobulin superfamily (IgSF) domains with a C-terminal fibrinogen-related domain (FreD) and participate in reactions against trematode parasites. From RNAseq data we assembled a de novo reference transcriptome of B. glabrata to investigate the diversity of FREP transcripts. This study increased over two-fold the number of bonafide FREP subfamilies and revealed important sequence diversity within FREP12 subfamily. We also report the discovery of related molecules that feature one or two IgSF domains associated with different C-terminal lectin domains, named C-type lectin-related proteins (CREPs) and Galectin-related protein (GREP). Together, the highly similar FREPs, CREPs and GREP were designated VIgL (Variable Immunoglobulin and Lectin domain containing molecules). PMID:25451302

  8. Topoisomerase I deficiency causes RNA polymerase II accumulation and increases AID abundance in immunoglobulin variable genes.

    PubMed

    Maul, Robert W; Saribasak, Huseyin; Cao, Zheng; Gearhart, Patricia J

    2015-06-01

    Activation-induced deaminase (AID) is a DNA cytosine deaminase that diversifies immunoglobulin genes in B cells. Recent work has shown that RNA polymerase II (Pol II) accumulation correlates with AID recruitment. However, a direct link between Pol II and AID abundance has not been tested. We used the DT40 B-cell line to manipulate levels of Pol II by decreasing topoisomerase I (Top1), which relaxes DNA supercoiling in front of the transcription complex. Top1 was decreased by stable transfection of a short hairpin RNA against Top1, which produced an accumulation of Pol II in transcribed genes, compared to cells transfected with sh-control RNA. The increased Pol II density enhanced AID recruitment to variable genes in the λ light chain locus, and resulted in higher levels of somatic hypermutation and gene conversion. It has been proposed by another lab that AID itself might directly suppress Top1 to increase somatic hypermutation. However, we found that in both AID(+/+) and AID(-/-) B cells from DT40 and mice, Top1 protein levels were identical, indicating that the presence or absence of AID did not decrease Top1 expression. Rather, our results suggest that the mechanism for increased diversity when Top1 is reduced is that Pol II accumulates and recruits AID to variable genes.

  9. The preferential codon usages in variable and constant regions of immunoglobulin genes are quite distinct from each other.

    PubMed

    Miyata, T; Hayashida, H; Yasunaga, T; Hasegawa, M

    1979-12-20

    The pattern of codon utilization in the variable and constant regions of immunoglobulin genes are compared. It is shown that, in these regions, codon utilizations are quite distinct from one another: For most degenerate codons, there is a selective bias that prefers C and/or G ending codons to U and/or A ending codons in the constant region compared with the bias in the variable region. This would strongly suggest that, in immunoglobulin genes, the bias in code word usage is determined by other factors than those concerning with the translational mechanism such as tRNA availability and codon-anticodon interaction. A possibility is also suggested that this differance of code word usage between them is due to the existence of secondary structure in the constant region but not in the variable region.

  10. Molecular characterization of the immunoglobulin light chain variable region repertoire of human autoantibodies

    SciTech Connect

    Victor, K.D.

    1992-01-01

    The molecular structures of the light chain variable regions encoding human autoantibodies have been studied in detail. The variable region repertoire among this group of antibodies is diverse. There is no evidence for preferential utilization of specific V[sub L] gene families or over-representation of certain V[sub L] gene segments in autoantibodies. Many autoreactive antibodies utilize direct copies of known germline gene segments with little evidence of somatic mutation, supporting the conclusion that at least some germline gene segments encode autoreactivity. Additionally, the structures of several autoantibodies are clearly the product of somatic mutation. Lastly, affinity maturation has been demonstrated in two clonally related IgM rheumatoid factors suggestive of an antigen driven response. The heterogeneity of the V[sub L] region repertoire in human autoantibodies challenges evidence in the literature suggesting that the majority of human autoantibodies utilize the same or closely related germline gene segments with no evidence of somatic mutation. In addition, this study has documented that variation in the length of the light chain is a common feature in human antibodies. Length variation is confined to the V[sub k]-J[sub k] joint of CDR3 and occurs in all V[sub k] gene families. Analysis of the structures of the V[sub k]-J[sub k] joints suggests that both germline derived and non-germline encoded nucleotides (N-segments), probably the result of terminal deoxynucleotidyl transferase activity, contribute to the junctional diversity of the immunoglobulin light chain variable region. Thus, length variation at the V[sub L]-J[sub L] joint is a frequent event having the potential to expand the diversity of the antibody molecule.

  11. Susceptibility to multiple sclerosis is associated with the proximal immunoglobulin heavy chain variable region.

    PubMed Central

    Walter, M A; Gibson, W T; Ebers, G C; Cox, D W

    1991-01-01

    15 immunoglobulin heavy chain constant (CH) and variable region (VH) polymorphisms were selected to span the entire length of the heavy chain cluster. These polymorphisms were examined in 34 sib pairs concordant for multiple sclerosis (MS) and in 23 sporadic MS patients. Allele frequencies were calculated for the 2 MS patient groups and compared with those found in a control population from the same geographical location and of similar ethnic background. No significant association was found between MS and the 7 CH region polymorphisms examined. However, a significant correlation between the MS phenotype and a VH2 family polymorphism was observed in both MS patient populations (familial MS patients chi 2 = 8.16, P less than 0.005; sporadic MS patients chi 2 = 8.90, P less than 0.005). One allele of the VH2-5 gene segment was found to be over-represented in both MS groups. VH2-5 has recently been physically mapped close to the CH region, between 180 and 360 kb away. These results indicate that a locus near or within the CH-proximal VH region is associated with increased susceptibility to MS. Images PMID:1672695

  12. Stochastic rearrangement of immunoglobulin variable-region genes in chicken B-cell development.

    PubMed Central

    Benatar, T; Tkalec, L; Ratcliffe, M J

    1992-01-01

    The molecular mechanism by which immunoglobulin (Ig) gene rearrangement occurs is highly conserved between mammalian and avian species. However, in avian species, an equivalent to the mammalian pre-B cell, which has undergone Ig heavy-chain gene rearrangement and expresses mu heavy chains in the absence of Ig light-chain rearrangement, has not been convincingly demonstrated. It is consequently unclear whether an ordered progression of gene rearrangement events leading to functional Ig expression occurs in avian species. To examine the sequence of Ig gene rearrangement events in chicken B-cell development, we transformed day 12 embryo bursal cells with the REV-T(CSV) retrovirus. More than 100 clones were analyzed by Southern blotting and polymerase chain reaction for the presence of Ig gene rearrangements. The majority of these clones contained only germline Ig sequences. Several clones contained complete heavy- and light-chain rearrangements and 13 clones contained only heavy-chain rearrangements analogous to stages of mammalian B-cell development. However, 5 clones contained rearrangements of light-chain genes in the absence of complete heavy-chain rearrangement. Consequently, we conclude that rearrangement of chicken Ig light-chain genes does not require heavy-chain variable-region rearrangement. This observation suggests that chicken Ig gene rearrangement events required for Ig expression occur stochastically rather than sequentially. Images PMID:1502173

  13. DNA sequence of immunoglobulin heavy chain variable region gene in thyroid lymphoma.

    PubMed

    Miwa, H; Takakuwa, T; Nakatsuka, S; Tomita, Y; Matsuzuka, F; Aozasa, K

    2001-10-01

    Patho-epidemiological studies have shown that thyroid lymphoma (TL) develops in thyroid affected by chronic lymphocytic thyroiditis (CLTH). CLTH is categorized as an organ-specific autoimmune disease, in which activated B-lymphocytes secrete a number of autoantibodies. Because antigenic stimulation might be involved in the pathogenesis of TL, the variable region in heavy chain (V(H)) genes was characterized in 13 cases with TL and 3 with CLTH. Clonal rearrangement of the V(H) gene was found in 11 cases of TL, and cloning study with sequencing of complimentary determining region (CDR) 3 revealed the presence of a major clone in 4. Three of the 4 cases used V(H) 3 gene, with the homologous germline gene of V3-30 in two cases and VH26 in one case. A biased usage of V(H) 3 and V(H) 4 genes with the homologous germline gene of VH26 in V(H) 3 gene was reported previously in cases with CLTH. A high level of somatic mutation (1-21%, average 12%) with non-random distribution of replacement and silent mutations was accumulated in all cases. The frequency of the occurrence of minor clones ranged from 29-44% per case, indicating the presence of on-going mutation. DNA sequencing of immunoglobulin V(H) gene suggests that TL develops among activated lymphoid cells in CLTH at the germinal center stage under antigen selection. PMID:11676854

  14. B cells in autoimmune diseases: Insights from analyses of immunoglobulin variable (Ig V) gene usage

    PubMed Central

    Foreman, Angela Lee; Van de Water, Judy; Gougeon, Marie-Lise; Gershwin, M. Eric

    2007-01-01

    The role of B cells in autoimmune diseases has not been fully elucidated. It is also unclear whether breaking of B cell tolerance in patients with autoimmune diseases is due to underlying defects in the molecular mechanisms involved in the arrangement of antibody genes or deficiencies in the subsequent selective influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig) variable (V) gene usage is beginning to provide answers to some of these questions. Such analyses have identified some differences in the basic Ig V gene repertoire of patients with autoimmune diseases compared to healthy controls, even though none of these differences can be considered major. Defects in positive and negative selection, mutational targeting and, in some cases, receptor editing have also been detected. In addition, analysis of Ig V gene usage in target organs and tissues of patients with autoimmune diseases have clearly demonstrated that there is a highly compartmentalized clonal expansion of B cells driven by a limited number of antigens in these tissues. Great progress has been made in the structural and functional characterization of disease-associated antibodies, largely because of the development of the combinatorial library technique. Use of antibodies generated by this technique offers great promise in identifying B cell epitopes on known target antigens and in gaining greater insights into the pathogenic role of B cells in both B- and T-cell-mediated autoimmune diseases. PMID:17537385

  15. Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.

    PubMed

    Tsao, B P; Ebling, F M; Roman, C; Panosian-Sahakian, N; Calame, K; Hahn, B H

    1990-02-01

    We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW F1 female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory.

  16. Mutation affecting the expression of immunoglobulin variable regions in the rabbit.

    PubMed

    Kelus, A S; Weiss, S

    1986-07-01

    We have found a variant of the allotype allele a2 in the rabbit, which presumably arose by mutation, that segregates as expected for an allele at the a locus. This allele is called "ali" and the corresponding rabbit strain is called "Alicia." In heterozygous animals (ali/a1 and ali/a3) the concentration of a2 molecules is lower by a factor of 1000 than in standard a2/a2 homozygotes. In homozygous ali/ali individuals the a2 concentration varies with age--i.e., very low in young rabbits and higher in older ones--but it never reaches normal levels. The low level of a2 is compensated by increased amounts of a-negative molecules. Southern blot analysis did not reveal any gross changes in the intron between JH and C mu (joining region of immunoglobulin heavy chain and constant region of immunoglobulin mu chain) or in the number of VH gene segments encoding a locus specificities. We suggest that the ali phenotype is due to a mutation in a control element.

  17. Anaphylaxis to IGIV in immunoglobulin-naïve common variable immunodeficiency patient in the absence of IgG anti-IgA antibodies: successful administration of low IgA-containing immunoglobulin.

    PubMed

    Gharib, Asal; Caperton, Caroline; Gupta, Sudhir

    2016-01-01

    Although severe reactions to immunoglobulin preparations have been frequently reported, IgE antibodies against IgA are usually not investigated; and occur predominantly in previously sensitized patients. The purpose is to report anaphylaxis to IGIV during initial infusion in a patient with common variable immunodeficiency with absent IgA without prior sensitization and in the absence of detectable IgG anti-IgA antibodies, and positive skin tests for immediate hypersensitivity to four different preparations of IGIV, one subcutaneous immunoglobulin preparation, and to purified IgA. Patient was treated without side effects with IGIV preparation depleted of IgA to which immediate hypersensitivity skin test was negative. This case demonstrates that patients with CVID with no IgA and without prior exposure to immunoglobulin or plasma may develop anaphylaxis following initial infusion of IGIV, which appears to be due to IgE anti-IgA, and independent of IgG anti-IgA antibodies. Since there is no good correlation between anaphylaxis/anaphylactic reactions and IgG anti-IgA antibodies, and IgE anti-IgA antibody test is commercially unavailable, we suggest that the patients with CVID with absence of IgA might be skin tested for immediate hypersensitivity prior to initiation of immunoglobulin administration. However, such recommendation may require studies on a large number of patients with CVID with no detectable IgA.

  18. Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma

    PubMed Central

    Schneider, Dunja; Dühren-von Minden, Marcus; Alkhatib, Alabbas; Setz, Corinna; van Bergen, Cornelis A. M.; Benkißer-Petersen, Marco; Wilhelm, Isabel; Villringer, Sarah; Krysov, Sergey; Packham, Graham; Zirlik, Katja; Römer, Winfried; Buske, Christian; Stevenson, Freda K.; Veelken, Hendrik

    2015-01-01

    B-cell antigen receptor (BCR) expression is a key feature of most B-cell lymphomas, but the mechanisms of BCR signal induction and the involvement of autoantigen recognition remain unclear. In follicular lymphoma (FL) B cells, BCR expression is retained despite a chromosomal translocation that links the antiapoptotic gene BCL2 to the regulatory elements of immunoglobulin genes, thereby disrupting 1 heavy-chain allele. A remarkable feature of FL-BCRs is the acquisition of potential N-glycosylation sites during somatic hypermutation. The introduced glycans carry mannose termini, which create potential novel binding sites for mannose-specific lectins. Here, we investigated the effect of N-linked variable-region glycosylation for BCR interaction with cognate antigen and with lectins of different origins. N-glycans were found to severely impair BCR specificity and affinity to the initial cognate antigen. In addition, we found that lectins from Pseudomonas aeruginosa and Burkholderia cenocepacia bind and stimulate FL cells. Human exposure to these bacteria can occur by contact with soil and water. In addition, they represent opportunistic pathogens in susceptible hosts. Understanding the role of bacterial lectins might elucidate the pathogenesis of FL and establish novel therapeutic approaches. PMID:25784678

  19. Restricted Immunoglobulin Variable Region (Ig V) Gene Expression Accompanies Secondary Rearrangements of Light Chain Ig V Genes in Mouse Plasmacytomas

    PubMed Central

    Diaw, Lena; Siwarski, David; Coleman, Allen; Kim, Jennifer; Jones, Gary M.; Dighiero, Guillaume; Huppi, Konrad

    1999-01-01

    The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructofuranans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (VL) and heavy (VH) variable region genes to express a characteristic monoclonal antibody. In this study, we have examined by enzyme-linked immunosorbent assay five antibodies secreted by silicone-induced mouse plasmacytomas using a broader panel of antigens including actin, myosin, tubulin, single-stranded DNA, and double-stranded DNA. We have determined the Ig heavy and light chain V gene usage in these same plasmacytomas at the DNA and RNA level. Our studies reveal: (a) antibodies secreted by plasmacytomas bind to different antigens in a manner similar to that observed for natural autoantibodies; (b) the expressed Ig heavy genes are restricted in V gene usage to the VH-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both κ and λ light chain genes. These results suggest that plasmacytomas use a restricted population of B cells that may still be undergoing rearrangement, thereby bypassing the allelic exclusion normally associated with expression of antibody genes. PMID:10562316

  20. Effect of Excipients on Liquid-Liquid Phase Separation and Aggregation in Dual Variable Domain Immunoglobulin Protein Solutions.

    PubMed

    Raut, Ashlesha S; Kalonia, Devendra S

    2016-03-01

    Liquid-liquid phase separation (LLPS) and aggregation can reduce the physical stability of therapeutic protein formulations. On undergoing LLPS, the protein-rich phase can promote aggregation during storage due to high concentration of the protein. Effect of different excipients on aggregation in protein solution is well documented; however data on the effect of excipients on LLPS is scarce in the literature. In this study, the effect of four excipients (PEG 400, Tween 80, sucrose, and hydroxypropyl beta-cyclodextrin (HPβCD)) on liquid-liquid phase separation and aggregation in a dual variable domain immunoglobulin protein solution was investigated. Sucrose suppressed both LLPS and aggregation, Tween 80 had no effect on either, and PEG 400 increased LLPS and aggregation. Attractive protein-protein interactions and liquid-liquid phase separation decreased with increasing concentration of HPβCD, indicating its specific binding to the protein. However, HPβCD had no effect on the formation of soluble aggregates and fragments in this study. LLPS and aggregation are highly temperature dependent; at low temperature protein exhibits LLPS, at high temperature protein exhibits aggregation, and at an intermediate temperature both phenomena occur simultaneously depending on the solution conditions.

  1. [Use of intravenous immunoglobulin in pregnancy. Report of a patient with common variable immunodeficiency].

    PubMed

    Cambray-Gutiérrez, Julio César; García-Ramírez, Ulises Noel; Del Rivero-Hernández, Leonel Gerardo; López-Pérez, Patricia; Chávez-García, Aurora

    2016-01-01

    Antecedentes: La inmunodeficiencia común variable es la inmunodeficiencia primaria más diagnosticada en los adultos; se caracteriza por infecciones sinopulmonares y gastrointestinales de repetición y mayor incidencia de procesos autoinmunes y malignidad. Numerosos pacientes inician con las manifestaciones clínicas durante la edad reproductiva. Caso clínico: Mujer de 34 años de edad con 12 semanas de gestación, en quien se diagnosticó inmunodeficiencia común variable después de cuadros recurrentes de rinosinusitis, faringoadmidalitis y neumonías. Durante el segundo trimestre se prescribió 0.6 g/kg de inmunoglobulina intravenosa cada 21 días; la paciente solo presentó un episodio de faringoamigdalitis, con adecuada respuesta al tratamiento con antibióticos. Durante el tercer trimestre se ajustó la dosis a cada 14 días. La paciente concluyó el embarazo a término sin complicaciones, con producto sin malformaciones y con peso y talla adecuados. Conclusiones: La administración de inmunoglobulina es el principal tratamiento para controlar la inmunodeficiencia común variable. Si bien la dosis inicial recomendada es de 400-800 mg/kg en forma intravenosa cada 3 a 4 semanas, no existe un consenso sobre la dosis que debe emplearse en la mujer que cursa con embarazo. La recomendación es realizar controles de niveles séricos antes de la infusión para determinarla y ajustarla.

  2. Immunoglobulins and immunoglobulin genes of the horse.

    PubMed

    Wagner, Bettina

    2006-01-01

    Antibodies of the horse were studied intensively by many notable immunologists throughout the past century until the early 1970's. After a large gap of interest in horse immunology, additional basic studies on horse immunoglobulin genes performed during the past 10 years have resulted in new insights into the equine humoral immune system. These include the characterization of the immunoglobulin lambda and kappa light chain genes, the immunoglobulin heavy chain constant (IGHC) gene regions, and initial studies regarding the heavy chain variable genes. Horses express predominately lambda light chains and seem to have a relatively restricted germline repertoire of both lambda and kappa chain variable genes. The IGHC region contains eleven constant heavy chain genes, seven of which are gamma heavy chain genes. It is suggested that all seven genes encoding IgG isotypes are expressed and have distinct functions in equine immune responses.

  3. Preferential utilization of conserved immunoglobulin heavy chain variable gene segments during human fetal life.

    PubMed Central

    Schroeder, H W; Wang, J Y

    1990-01-01

    The ability to respond to specific antigens develops in a programmed fashion. Although the antibody repertoire in adults is presumably generated by stochastic combinatorial joining of rearranged heavy variable, diversity, and joining (VH-DH-JH) and light (VL-JL) chains, experimental evidence in the mouse has shown nonrandom utilization of variable gene segments during ontogeny and in response to specific antigens. In this study, we have performed sequence analysis of 104-day human fetal liver-derived, randomly isolated constant region C+ mu transcripts and demonstrate a consistent preference during fetal life for a small subset of three highly conserved VH3 family gene segments. In addition, the data show that this preferential gene segment utilization extends to the DHQ52 and the JH3 and JH4 loci. Sequence analysis of two "sterile" DH-JH transcripts suggests that transcriptional activation of the JH-proximal DHQ52 element may precede initiation of DH-JH rearrangement and influence fetal DH utilization. Sequence comparisons reveal striking nucleotide polymorphism in allelic gene segments which is poorly reflected in the peptide sequence, implying considerable evolutionary selection pressure. Although vertebrate species utilize a variety of strategies to generate their antibody repertoire, preferential utilization of VH3 elements is consistently found during early development. These data support the hypothesis that VH3 gene segments play an essential role in the development of the immune response. Images PMID:2117273

  4. Shared idiotypes and restricted immunoglobulin variable region heavy chain genes characterize murine autoantibodies of various specificities.

    PubMed Central

    Monestier, M; Manheimer-Lory, A; Bellon, B; Painter, C; Dang, H; Talal, N; Zanetti, M; Schwartz, R; Pisetsky, D; Kuppers, R

    1986-01-01

    The study of the Ig variable region heavy chain (VH) genes used to encode antibodies specific for self-epitopes from murine hybridomas showed that three VH families are primarily utilized: VH J558, the largest family, and VH QPC52 and VH 7183, the families most proximal to the Ig joining region heavy chain genes. These monoclonal autoantibodies express cross-reactive idiotopes shared by rheumatoid factors and antibodies specific for Sm. The expression of these idiotypes is independent of major histocompatibility complex and Ig constant region heavy chain haplotypes, self-antigen specificity, and even the VH gene family utilized. Though the experiments described here are limited to murine autoantibodies, similarities exist between murine and human autoimmune diseases. Studies that aim to investigate the relationship between VH gene expression and the presence of cross-reactive idiotypes among human autoantibodies should enable us to better understand the mechanisms of autoimmunity and self-tolerance. Images PMID:2427543

  5. [Adverse effects with ambulatory intravenous immunoglobulin administration in adult patients with common variable immunodeficiency].

    PubMed

    Rodríguez-Mireles, Karen A; Galguera-Sauceda, Angélica; Gaspar-López, Arturo; López-Rocha, Eunice G; Campos-Romero, Freya; Del Rivero-Hernández, Leonel; Amaya-Mejía, Adela; Galindo-Pacheco, Lucy; O'Farril-Romanillos, Patricia; Segura-Méndez, Nora Hilda

    2014-01-01

    Antecedentes: la inmunodeficiencia común variable es la inmunodeficiencia primaria sintomática más frecuente, afecta a 1 por cada 25,000 a 75,000 sujetos. Se distingue por la ausencia o disminución de anticuerpos. Su tratamiento consiste en el reemplazo de anticuerpos con inmunoglobulina humana y la vía de administración más frecuente es la intravenosa, a dosis de 400 a 800 mg/kg de peso/dosis cada tres a cuatro semanas. Los efectos adversos asociados con la administración de inmunoglobulina intravenosa (IgIV) ocurren incluso en 25% de todas las infusiones realizadas, las reacciones severas afectan a menos de 1% de los pacientes. Entre las reacciones adversas severas están la insuficiencia renal aguda, que sobreviene 1 a 10 días después del inicio de tratamiento con IgIV. En nuestro centro elaboramos e implementamos un esquema ambulatorio para la aplicación de IgIV que permite su administración en un promedio de 3 h, sin efectos adversos graves. Objetivos: describir los efectos adversos y evaluar la frecuencia de insuficiencia renal secundaria a la aplicación ambulatoria de IgIV en pacientes adultos con inmunodeficiencia común variable. Material y método: estudio descriptivo y prospectivo en el que participaron pacientes adultos con diagnóstico definitivo de inmunodeficiencia común variable, que recibían IgIV a dosis de sustitución cada tres semanas, a quienes se realizó exploración física, somatometría, determinación sérica de creatinina, albúmina y urea, depuración de creatinina en orina de 24 horas, cálculo de la tasa de filtración glomerular por la fórmula CKD-EPI y evaluación de la función renal inmediata, así como la asociada con la administración acumulada de IgIV a través del cálculo de la tasa de filtración glomerular. Los resultados se analizaron con estadística descriptiva para el reporte de los efectos en la función renal y la dosis acumulada de IgIV. Resultados: se determinó la frecuencia de reacciones adversas

  6. Circular Dichroism Reveals Evidence of Coupling Between Immunoglobulin Constant and Variable Region Secondary Structure†

    PubMed Central

    Janda, Alena; Casadevall, Arturo

    2010-01-01

    Antibodies (Ab) are bifunctional molecules with two domains, a constant region (C) that confers effector properties and a variable (V) region responsible of antigen (Ag) binding. Historically the C and V regions were considered to be functionally independent, with Ag specificity being solely determined by the V region. However, recent studies suggest that the C region can affect Ab fine specificity. This has led to the proposal that the CH domain influences the structure of the V region, thus affecting Ab affinity and fine specificity. An inference from this proposal is that V region identical monoclonal Abs (mAbs) differing in C region (eg isotype) would manifest different secondary structures arising from isotype-induced variation in the V-C region after Ag binding. We hypothesized that such effects could translate into differences in Circular Dichroism (CD) upon Ag-Ab complex formation. Consequently we studied the interaction of a set of V region identical IgG1, IgG2a, IgG2b, and IgG3 mAbs with glucuronoxylomannan (GXM). The native CD spectra of the pairs IgG1/IgG2a and IgG3/IgG2b were strikingly similar, implying similar secondary structure content. GXM binding by IgG1, IgG2a, IgG2b and IgG3 produced different CD changes, with the pairs IgG1/IgG2a and IgG3/IgG2b again manifesting qualitatively similar trends in secondary structure changes. The magnitude of the changes differed among the isotypes with IgG2a > IgG3> IgG2b> IgG1. These differences in CD changes were interpreted to reflect differences in V-C secondary structure. PMID:20299100

  7. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin

    PubMed Central

    Ameratunga, R; Woon, S-T; Gillis, D; Koopmans, W; Steele, R

    2013-01-01

    Common variable immune deficiency (CVID) is the most frequent symptomatic primary immune deficiency in adults. The standard of care is intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (scIG) therapy. The cause of CVID is currently unknown, and there is no universally accepted definition of CVID. This creates problems in determining which patients will benefit from IVIG/scIG treatment. In this paper, we review the difficulties with the commonly used European Society of Immune Deficiencies (ESID) and the Pan American Group for Immune Deficiency (PAGID) definition of CVID. We propose new criteria for the diagnosis of CVID, which are based on recent scientific discoveries. Improved diagnostic precision will assist with treatment decisions including IVIG/scIG replacement. We suggest that asymptomatic patients with mild hypogammaglobulinaemia are termed hypogammaglobulinaemia of uncertain significance (HGUS). These patients require long-term follow-up, as some will evolve into CVID. PMID:23859429

  8. Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress.

    PubMed

    Chen, Zengsheng; Mondal, Nandan K; Ding, Jun; Koenig, Steven C; Slaughter, Mark S; Griffith, Bartley P; Wu, Zhongjun J

    2015-11-01

    The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay. In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induce a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood-contacting medical devices. PMID:26160282

  9. Acute transient non-physiological over-sensing in the ventricle with a DF4 lead

    PubMed Central

    Ng, Kevin Kit; Gould, Paul A.

    2015-01-01

    The DF-4 is a new defibrillator lead technology. We present two cases of non-physiological transient ventricular over-sensing in patients who underwent implantation of an ICD for secondary prevention. Case 1 had ventricular over-sensing during pacing threshold evaluation post defibrillation testing while Case 2 had the lead integrity alert triggered immediately post discharge with transient over-sensing. No lead-connector issues were found. Case 1 was likely due to improper venting of the header and trapped air. Case 2 was hypothesized to be due to intermittent header pin non-contact secondary to blood in the header. These cases reveal that DF-4 leads are subject to both reported and potentially novel causes of transient acute ventricular over-sensing. PMID:26937124

  10. Total Proteome Analysis Identifies Migration Defects as a Major Pathogenetic Factor in Immunoglobulin Heavy Chain Variable Region (IGHV)-unmutated Chronic Lymphocytic Leukemia*

    PubMed Central

    Eagle, Gina L.; Zhuang, Jianguo; Jenkins, Rosalind E.; Till, Kathleen J.; Jithesh, Puthen V.; Lin, Ke; Johnson, Gillian G.; Oates, Melanie; Park, Kevin; Kitteringham, Neil R.; Pettitt, Andrew R.

    2015-01-01

    The mutational status of the immunoglobulin heavy chain variable region defines two clinically distinct forms of chronic lymphocytic leukemia (CLL) known as mutated (M-CLL) and unmutated (UM-CLL). To elucidate the molecular mechanisms underlying the adverse clinical outcome associated with UM-CLL, total proteomes from nine UM-CLL and nine M-CLL samples were analyzed by isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. Based on the expression of 3521 identified proteins, principal component analysis separated CLL samples into two groups corresponding to immunoglobulin heavy chain variable region mutational status. Computational analysis showed that 43 cell migration/adhesion pathways were significantly enriched by 39 differentially expressed proteins, 35 of which were expressed at significantly lower levels in UM-CLL samples. Furthermore, UM-CLL cells underexpressed proteins associated with cytoskeletal remodeling and overexpressed proteins associated with transcriptional and translational activity. Taken together, our findings indicate that UM-CLL cells are less migratory and more adhesive than M-CLL cells, resulting in their retention in lymph nodes, where they are exposed to proliferative stimuli. In keeping with this hypothesis, analysis of an extended cohort of 120 CLL patients revealed a strong and specific association between UM-CLL and lymphadenopathy. Our study illustrates the potential of total proteome analysis to elucidate pathogenetic mechanisms in cancer. PMID:25645933

  11. Crystallization and preliminary X-ray diffraction analysis of a single variable domain of the immunoglobulin superfamily in amphioxus, Amphi-IgSF-V.

    PubMed

    Jiang, Bo; Liu, Yanjie; Chen, Rong; Wang, Zhenbao; Tariq, Mansoor; Xia, Chun

    2014-08-01

    Amphioxus is regarded as an essential animal model for the study of immune evolution. Discovery of new molecules with the immunoglobulin superfamily (IgSF) variable (V) domain in amphioxus would help in studying the evolution of IgSF V molecules in the immune system. A protein was found which just contains only one IgSF V domain in amphioxus, termed Amphi-IgSF-V; it has over 30% sequence identity to the V domains of human immunoglobulins and mammalian T-cell receptors. In order to clarify the three-dimensional structure of this new molecule in amphioxus, Amphi-IgSF-V was expressed, purified and crystallized, and diffraction data were collected to a resolution of 1.95 Å. The crystal belonged to space group P3221, with unit-cell parameters a = b = 53.9, c = 135.5 Å. The Matthews coefficient and solvent content were calculated to be 2.58 Å(3) Da(-1) and 52.38%, respectively. The results will provide structural information to study the evolution of IgSF V molecules in the immune system.

  12. Crystallization and preliminary X-ray diffraction analysis of a single variable domain of the immunoglobulin superfamily in amphioxus, Amphi-IgSF-V.

    PubMed

    Jiang, Bo; Liu, Yanjie; Chen, Rong; Wang, Zhenbao; Tariq, Mansoor; Xia, Chun

    2014-08-01

    Amphioxus is regarded as an essential animal model for the study of immune evolution. Discovery of new molecules with the immunoglobulin superfamily (IgSF) variable (V) domain in amphioxus would help in studying the evolution of IgSF V molecules in the immune system. A protein was found which just contains only one IgSF V domain in amphioxus, termed Amphi-IgSF-V; it has over 30% sequence identity to the V domains of human immunoglobulins and mammalian T-cell receptors. In order to clarify the three-dimensional structure of this new molecule in amphioxus, Amphi-IgSF-V was expressed, purified and crystallized, and diffraction data were collected to a resolution of 1.95 Å. The crystal belonged to space group P3221, with unit-cell parameters a = b = 53.9, c = 135.5 Å. The Matthews coefficient and solvent content were calculated to be 2.58 Å(3) Da(-1) and 52.38%, respectively. The results will provide structural information to study the evolution of IgSF V molecules in the immune system. PMID:25084385

  13. A soluble immunoglobulin variable domain without a disulfide bridge: construction, accumulation in the cytoplasm of E. coli, purification and physicochemical characterization.

    PubMed

    Frisch, C; Kolmar, H; Fritz, H J

    1994-05-01

    Two amino acid exchanges (Y32H and C23V) were introduced sequentially into the immunoglobulin REIV, a human kappa variable domain. The first exchange stabilizes the folded state of the domain by 4.6 kJ/mol (1.1 kcal/mol), the second abolishes the central disulfide bridge and destabilizes the folded domain by 17.5 kJ/mol (4.2 kcal/mol). Introduction of the stabilizing exchange first is a necessary pre-requisite to the removal of the central disulfide bridge without collapse of the fold. The double mutant REIV-C23V/Y32H can be accumulated in the cytoplasmatic compartment of the E. coli cell, a finding that opens new possibilities in antibody engineering.

  14. Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague-Dawley rats.

    PubMed

    Basu, Tapan K; Makhani, Neelam; Sedgwick, Gary

    2002-02-01

    Niacin (nicotinic acid) in its non-physiological dose level is known to be an effective lipid-lowering agent; its potential risk as a therapeutic agent, however, has not been critically considered. Since niacin is excreted predominantly as methylated pyridones, requiring methionine as a methyl donor, the present study was undertaken to examine whether metabolism of the amino acid is altered in the presence of large doses of niacin. Male Sprague-Dawley rats were given a nutritionally adequate, semi-synthetic diet containing niacin at a level of either 400 or 1000mg/kg diet (compared to 30mg/kg in the control diet) for up to 3 months. Supplementation with niacin (1,000 mg/kg diet) for 3 months resulted in a significant increase in plasma and urinary total homocysteine levels; this increase was further accentuated in the presence of a high methionine diet. The hyperhomocysteineaemia was accompanied by a significant decrease in plasma concentrations of vitamins B6 and B12, which are cofactors for the metabolism of homocysteine. The homocysteine-raising action of niacin, in particular, has an important toxicological implication, as hyperhomocysteineaemia is considered to be an independent risk factor for arterial occlusive disease. The niacin-associated change in homocysteine status may be an important limiting factor in the use of this vitamin as a lipid-lowering agent.

  15. Bronchoalveolar lavage of cranial and caudal lung regions in selected normal calves: cellular, microbiological, immunoglobulin, serological and histological variables.

    PubMed Central

    Pringle, J K; Viel, L; Shewen, P E; Willoughby, R A; Martin, S W; Valli, V E

    1988-01-01

    Of a group of 30 clinically normal male Holstein calves two to eight weeks of age, six two week old and six four week old calves met various radiographical and clinicopathological criteria for normality. Bronchoalveolar lavage was performed by fiberoptic bronchoscopy on cranial and caudal lung regions in all 30 calves and samples analyzed for free cells, microorganisms, and immunoglobulins. Lateral chest radiographs and lung biopsies were also conducted on each calf. Calves were euthanized and necropsied ten days after bronchoalveolar lavage was conducted. Reported in this paper are results from the 12 normal calves. Microorganisms were present in small numbers in the lower respiratory tract of some normal calves. There were no differences in the above parameters between cranial and caudal lobes. There were statistically significant changes in bronchoalveolar lavage cell proportions with age although there were no detectable differences in clinical signs. Four week old calves had a lower percentage of macrophages and a higher percentage of epithelial cells than two week old animals (p less than 0.05). There was also a trend toward an increased percentage of neutrophils in older calves but this was not significant (p greater than 0.05). Total bronchoalveolar lavage protein also appeared to increase with age (p less than 0.05). In both groups a higher proportion of IgG2 in bronchoalveolar lavage compared to serum was found, suggesting the presence of a local selective transfer mechanism into respiratory secretions. Images Fig. 2. Fig. 3. Fig. 4. PMID:3370559

  16. Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor

    PubMed Central

    Gouilleux-Gruart, V; Chapel, H; Chevret, S; Lucas, M; Malphettes, M; Fieschi, C; Patel, S; Boutboul, D; Marson, M-N; Gérard, L; Lee, M; Watier, H; Oksenhendler, E

    2013-01-01

    Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An ‘efficiency’ index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig. PMID:23286945

  17. Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor.

    PubMed

    Gouilleux-Gruart, V; Chapel, H; Chevret, S; Lucas, M; Malphettes, M; Fieschi, C; Patel, S; Boutboul, D; Marson, M-N; Gérard, L; Lee, M; Watier, H; Oksenhendler, E

    2013-02-01

    Treatment of common variable immunodeficiency disorders (CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin (Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An 'efficiency' index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route (P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) (P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat (VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain (FCGRT)] promoter, and this was particularly significant in patients treated with IVIG (P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype (P = 0·008) and high serum albumin (P < 0·001) were associated independently with increased efficiency of i.v. Ig. PMID:23286945

  18. Immunoglobulin variable gene segment V{sub H}81X of the mouse is embedded in L1 transposon sequences

    SciTech Connect

    Bachl, J.; Defranoux, N.; Wabl, M.

    1995-01-11

    L1 elements are widely distributed over the mammalian genome, but the question of their biological significance is still open. The mouse heavy (H) chain variable region V{sub H}81X is overrepresented in the pre-B-cell repertoire; the significance of this is controversial, and V{sub H}81X has been the subject of much research. Here we present data showing that the mouse H chain variable region X{sub H}81X is embedded in the remnants of a LINE-1 element.

  19. Altered phenotypic expression of immunoglobulin heavy-chain variable-region (VH) genes in Alicia rabbits probably reflects a small deletion in the VH genes closest to the joining region.

    PubMed

    Allegrucci, M; Newman, B A; Young-Cooper, G O; Alexander, C B; Meier, D; Kelus, A S; Mage, R G

    1990-07-01

    Rabbits of the Alicia strain have a mutation (ali) that segregates with the immunoglobulin heavy-chain (lgh) locus and has a cis effect upon the expression of heavy-chain variable-region (VH) genes encoding the a2 allotype. In heterozygous a1/ali or a3/ali rabbits, serum immunoglobulins are almost entirely the products of the normal a1 or a3 allele and only traces of a2 immunoglobulin are detectable. Adult homozygous ali/ali rabbits likewise have normal immunoglobulin levels resulting from increased production of a-negative immunoglobulins and some residual ability to produce the a2 allotype. By contrast, the majority of the immunoglobulins of wild-type a2 rabbits are a2-positive and only a small percentage are a-negative. Genomic DNAs from homozygous mutant and wild-type animals were indistinguishable by Southern analyses using a variety of restriction enzyme digests and lgh probes. However, when digests with infrequently cutting enzymes were analyzed by transverse alternating-field electrophoresis, the ali DNA fragments were 10-15 kilobases smaller than the wild type. These fragments hybridized to probes both for VH and for a region of DNA a few kilobases downstream of the VH genes nearest the joining region. We suggest that this relatively small deletion affects a segment containing 3' VH genes with important regulatory functions, the loss of which leads to the ali phenotype. These results, and the fact that the 3' VH genes rearrange early in B-cell development, indicate that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression.

  20. Liquid-Liquid Phase Separation in a Dual Variable Domain Immunoglobulin Protein Solution: Effect of Formulation Factors and Protein-Protein Interactions.

    PubMed

    Raut, Ashlesha S; Kalonia, Devendra S

    2015-09-01

    Dual variable domain immunoglobulin proteins (DVD-Ig proteins) are large molecules (MW ∼ 200 kDa) with increased asymmetry because of their extended Y-like shape, which results in increased formulation challenges. Liquid-liquid phase separation (LLPS) of protein solutions into protein-rich and protein-poor phases reduces solution stability at intermediate concentrations and lower temperatures, and is a serious concern in formulation development as therapeutic proteins are generally stored at refrigerated conditions. In the current work, LLPS was studied for a DVD-Ig protein molecule as a function of solution conditions by measuring solution opalescence. LLPS of the protein was confirmed by equilibrium studies and by visually observing under microscope. The protein does not undergo any structural change after phase separation. Protein-protein interactions were measured by light scattering (kD) and Tcloud (temperature that marks the onset of phase separation). There is a good agreement between kD measured in dilute solution with Tcloud measured in the critical concentration range. Results indicate that the increased complexity of the molecule (with respect to size, shape, and charge distribution on the molecule) increases contribution of specific and nonspecific interactions in solution, which are affected by formulation factors, resulting in LLPS for DVD-Ig protein.

  1. Restricted use of fetal VH3 immunoglobulin genes by unselected B cells in the adult. Predominance of 56p1-like VH genes in common variable immunodeficiency.

    PubMed

    Braun, J; Berberian, L; King, L; Sanz, I; Govan, H L

    1992-05-01

    The large VH3 family of human immunoglobulin genes is commonly used throughout B cell ontogeny. However, B cells of the fetus and certain autoantibody-producing clones are restricted to a recurrent subset of VH3 genes, and VH3 B cells are deficient in certain immunodeficiency diseases. In this study, we have sequenced a set of rearranged VH3 genes generated by genomic polymerase chain reaction (PCR) from normal adults and those with common variable immunodeficiency (CVI). In both groups, all cones were readily identifiable with the fetal VH3 subset, and were further distinguished by limited DH motifs and exclusive use of JH4. In CVI, the residual population of VH3 B cells were notable for predominant use of 56p1-like VH genes. All clones displayed sequence divergence (including somatic mutation) with evidence of strong selection against complementarity-determining region (CDR) coding change. A survey of other V gene families indicates that human V gene diversity may be restricted in general by germline mechanisms. These findings suggest that the expressed antibody repertoire in the human adult may be much smaller than anticipated, and selected by processes in part distinct from the paradigm of maximal antigen-binding diversity.

  2. Variable region sequences and idiotypic expression of a protective human immunoglobulin M antibody to capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1.

    PubMed Central

    Azmi, F H; Lucas, A H; Raff, H V; Granoff, D M

    1994-01-01

    We determined the heavy (H)- and light (L)-chain variable (V) region nucleotide and translated amino acid sequences of the human immunoglobulin M(kappa) monoclonal antibody (MAb) 5E1, which is specific for the polysaccharide capsule of Escherichia coli K1 and Neisseria meningitidis group B (poly[alpha(2-->8)-N-acetylneuraminic acid]) and which is protective in animal models of infection. The 5E1 VH gene is a member of the VHIIIb family and is 97% homologous to the 9.1 germ line gene. The 5E1 VL gene is a member of the kappa I subgroup and is 98% homologous to the germ line gene, 15A, also known as KLO12. The VL and/or VH genes used by 5E1 are highly homologous to the V genes encoding antibodies to the Haemophilus influenzae type b polysaccharide and to antibodies reactive with self-antigens such as erythrocyte "i," DNA, and thyroid peroxidase. We also produced three murine anti-idiotype (Id) MAbs against 5E1. All three anti-Ids recognize a minor subset of antimeningococcal B polysaccharide antibodies present in serum from normal adults. Two of the anti-Ids define distinct Ids associated with antibodies having kappa I-15A V regions. These 15A-associated Ids are expressed by some heterologous human antimeningococcal B polysaccharide MAbs, and they also are independently expressed by two human MAbs that are specific for either the H. influenzae b polysaccharide or the i erythrocyte antigen and that utilize the kappa I-15A V region. Taken together, these data indicate that the 5E1 antibody uses V regions that recur in the human antibody repertoires to this polysaccharide and to structurally dissimilar polysaccharides and autoantigens. Thus, the poor immunogenicity of poly[alpha(2-->8)-N-acetylneuraminic acid] cannot be explained by the unavailability of certain critical VH and VL genes required for generation of antibody response. PMID:8168940

  3. Immunoglobulin E in histoplasmosis.

    PubMed Central

    Cox, R A; Arnold, D R

    1980-01-01

    Immunoglobulin M, G, A, and E serum levels were quantitated in 20 patients with active histoplasmosis (group I), 24 healthy subjects who were skin test positive to histoplasmin (group II), and 47 healthy persons who were skin test negative to histoplasmin (group III). The results established that patients with this disease have increased immunoglobulin G (P less than 0.05), immunoglobulin A (P less than 0.001), and immunoglobulin E (P less than 0.01) serum levels when compared with the 71 healthy subjects in groups II and III. PMID:7399706

  4. Pulse wave analysis in a 180-degree curved artery model: Implications under physiological and non-physiological inflows

    NASA Astrophysics Data System (ADS)

    Bulusu, Kartik V.; Plesniak, Michael W.

    2013-11-01

    Systolic and diastolic blood pressures, pulse pressures, and left ventricular hypertrophy contribute to cardiovascular risks. Increase of arterial stiffness due to aging and hypertension is an important factor in cardiovascular, chronic kidney and end-stage-renal-diseases. Pulse wave analysis (PWA) based on arterial pressure wave characteristics, is well established in clinical practice for evaluation of arterial distensibility and hypertension. The objective of our exploratory study in a rigid 180-degree curved artery model was to evaluate arterial pressure waveforms. Bend upstream conditions were measured using a two-component, two-dimensional, particle image velocimeter (2C-2D PIV). An ultrasonic transit-time flow meter and a catheter with a MEMS-based solid state pressure sensor, capable of measuring up to 20 harmonics of the observed pressure waveform, monitored flow conditions downstream of the bend. Our novel continuous wavelet transform algorithm (PIVlet 1.2), in addition to detecting coherent secondary flow structures is used to evaluate arterial pulse wave characteristics subjected to physiological and non-physiological inflows. Results of this study will elucidate the utility of wavelet transforms in arterial function evaluation and pulse wave speed. Supported by NSF Grant No. CBET- 0828903 and GW Center for Biomimetics and Bioinspired Engineering.

  5. Computational Study of Non-Physiological Hemodynamics in the Cephalic Arch

    NASA Astrophysics Data System (ADS)

    Cassel, Kevin; Boghosian, Michael; Mahmoudzadeh, S. M. Javid; Hammes, Mary

    2012-11-01

    Numerical simulations of the unsteady, two-dimensional, incompressible Navier-Stokes equations are performed for the flow in a two-dimensional geometry created from radiological images and Doppler flow measurements of the cephalic arch in dialysis patients with a brachiocephalic fistula (surgically placed direct arterial-venous connection). The simulations are performed before insertion of the fistula and at subsequent time intervals as the cephalic vein arterializes over a period of three to six months. A mature fistula, with increased diameter and flow rate, can exhibit Reynolds numbers that are more than one order of magnitude larger than that of the pre-fistula vein. We evaluate the effect of this increased (physiologically abnormal) Reynolds number on flow structures and wall shear stresses through the curved cephalic arch, which is a site prone to stenosis in fistula patients. The long-term goal is to investigate if the development of initimal hyperplasia and stenoses correlates with wall shear stresses or other hemodynamic variables obtained using computational hemodynamics. Research supported by the National Institute of Diabetes And Digestive And Kidney Diseases of the National Institutes of Health under Award Number R01DK090769.

  6. NON-PHYSIOLOGICAL AMINO ACID (NPAA) THERAPY TARGETING BRAIN PHENYLALANINE REDUCTION: PILOT STUDIES IN PAHENU2 MICE

    PubMed Central

    Vogel, Kara R.; Arning, Erland; Wasek, Brandi L.; Bottiglieri, Teodoro; Gibson, K. Michael

    2012-01-01

    Transport of large neutral amino acids (LNAA) across the blood brain barrier (BBB) is facilitated by the L-type amino acid transporter, LAT1. Peripheral accumulation of one LNAA (e.g., phenylalanine (phe) in PKU) is predicted to increase uptake of the offending amino acid to the detriment of others, resulting in disruption of brain amino acid homeostasis. We hypothesized that selected non-physiological amino acids (NPAAs) such as DL-norleucine (NL), 2-aminonorbornane (NB; 2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid), 2-aminoisobutyrate (AIB), and N-methyl-aminoisobutyrate (MAIB), acting as competitive inhibitors of various brain amino acid transporters, could reduce brain phe in Pahenu2 mice, a relevant murine model of PKU. Oral feeding of 5% NL, 5% AIB, 0.5% NB and 3% MAIB reduced brain phe by 56% (p<0.01), −1% (p=NS), 27% (p<0.05) and 14% (p<0.01), respectively, compared to untreated subjects. Significant effects on other LNAAs (tyrosine, methionine, branched chain amino acids) were also observed, however, with MAIB displaying the mildest effects. Of interest, MAIB represents an inhibitor of the system A (alanine) transporter that primarily traffics small amino acids and not LNAAs. Our studies represent the first in vivo use of these NPAAs in Pahenu2 mice, and provide proof-of-principle for their further preclinical development, with the long-term objective of identifying NPAA combinations and concentrations that selectively restrict brain phe transport while minimally impacting other LNAAs and downstream intermediates. PMID:22976763

  7. Non-physiological amino acid (NPAA) therapy targeting brain phenylalanine reduction: pilot studies in PAHENU2 mice.

    PubMed

    Vogel, Kara R; Arning, Erland; Wasek, Brandi L; Bottiglieri, Teodoro; Gibson, K Michael

    2013-05-01

    Transport of large neutral amino acids (LNAA) across the blood brain barrier (BBB) is facilitated by the L-type amino acid transporter, LAT1. Peripheral accumulation of one LNAA (e.g., phenylalanine (phe) in PKU) is predicted to increase uptake of the offending amino acid to the detriment of others, resulting in disruption of brain amino acid homeostasis. We hypothesized that selected non-physiological amino acids (NPAAs) such as DL-norleucine (NL), 2-aminonorbornane (NB; 2-aminobicyclo-(2,1,1)-heptane-2-carboxylic acid), 2-aminoisobutyrate (AIB), and N-methyl-aminoisobutyrate (MAIB), acting as competitive inhibitors of various brain amino acid transporters, could reduce brain phe in Pah (enu2) mice, a relevant murine model of PKU. Oral feeding of 5 % NL, 5 % AIB, 0.5 % NB and 3 % MAIB reduced brain phe by 56 % (p < 0.01), -1 % (p = NS), 27 % (p < 0.05) and 14 % (p < 0.01), respectively, compared to untreated subjects. Significant effects on other LNAAs (tyrosine, methionine, branched chain amino acids) were also observed, however, with MAIB displaying the mildest effects. Of interest, MAIB represents an inhibitor of the system A (alanine) transporter that primarily traffics small amino acids and not LNAAs. Our studies represent the first in vivo use of these NPAAs in Pah (enu2) mice, and provide proof-of-principle for their further preclinical development, with the long-term objective of identifying NPAA combinations and concentrations that selectively restrict brain phe transport while minimally impacting other LNAAs and downstream intermediates.

  8. Equine immunoglobulins and organization of immunoglobulin genes.

    PubMed

    Walther, Stefanie; Rusitzka, Tamara V; Diesterbeck, Ulrike S; Czerny, Claus-Peter

    2015-12-01

    Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allelic variants are observed for IGLC1, IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age development, a decrease in IGLVs is noted, although nucleotide diversity and significant differences in gene usage increased. The following paper suggests a standardization of the existing nomenclature of immunoglobulin genes.

  9. The molecular basis of somatic hypermutation of immunoglobulin genes.

    PubMed

    Storb, U

    1996-04-01

    Somatic hypermutation amplifies the variable region repertoire of immunoglobulin genes. Recent experimental evidence has thrown light on various molecular models of somatic hypermutation. A link between somatic hypermutation and transcription coupled DNA repair is shaping up.

  10. Organization of immunoglobulin genes.

    PubMed

    Tonegawa, S; Brack, C; Hozumi, N; Pirrotta, V

    1978-01-01

    The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

  11. Molecular basis for expression of the A48 regulatory idiotope on antibodies encoded by immunoglobulin variable-region genes from various families.

    PubMed Central

    Zaghouani, H; Bonilla, F A; Meek, K; Bona, C

    1989-01-01

    The idiotype defined by the levan-specific BALB/c myeloma protein ABPC48 (A48) has previously been encountered only in antibodies the variable regions of which derive from the VHX24 and V kappa 10 gene families. We have demonstrated expression of the idiotope recognized by the monoclonal anti-A48 idiotype antibody IDA10 on five monoclonal antibodies from different mouse strains, with different specificities including foreign and self antigens and deriving their variable regions from families other than VHX24 and V kappa 10. We analyzed variable region protein structure (deduced from nucleotide sequences) and hydrophilicity profiles of idiotype+ and idiotype- antibodies. We identified four surface-exposed areas (one in the heavy chain and three in the light chain) that may contribute to expression of the idiotope defined by antibody IDA10. Images PMID:2494665

  12. Molecular basis for expression of the A48 regulatory idiotope on antibodies encoded by immunoglobulin variable-region genes from various families.

    PubMed

    Zaghouani, H; Bonilla, F A; Meek, K; Bona, C

    1989-04-01

    The idiotype defined by the levan-specific BALB/c myeloma protein ABPC48 (A48) has previously been encountered only in antibodies the variable regions of which derive from the VHX24 and V kappa 10 gene families. We have demonstrated expression of the idiotope recognized by the monoclonal anti-A48 idiotype antibody IDA10 on five monoclonal antibodies from different mouse strains, with different specificities including foreign and self antigens and deriving their variable regions from families other than VHX24 and V kappa 10. We analyzed variable region protein structure (deduced from nucleotide sequences) and hydrophilicity profiles of idiotype+ and idiotype- antibodies. We identified four surface-exposed areas (one in the heavy chain and three in the light chain) that may contribute to expression of the idiotope defined by antibody IDA10.

  13. Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-IgTM) molecule that specifically and potently neutralizes both IL-1α and IL-1β

    PubMed Central

    Lacy, Susan E; Wu, Chengbin; Ambrosi, Dominic J; Hsieh, Chung-Ming; Bose, Sahana; Miller, Renee; Conlon, Donna M; Tarcsa, Edit; Chari, Ravi; Ghayur, Tariq; Kamath, Rajesh V

    2015-01-01

    Interleukin-1 (IL-1) cytokines such as IL-1α, IL-1β, and IL-1Ra contribute to immune regulation and inflammatory processes by exerting a wide range of cellular responses, including expression of cytokines and chemokines, matrix metalloproteinases, and nitric oxide synthetase. IL-1α and IL-1β bind to IL-1R1 complexed to the IL-1 receptor accessory protein and induce similar physiological effects. Preclinical and clinical studies provide significant evidence for the role of IL-1 in the pathogenesis of osteoarthritis (OA), including cartilage degradation, bone sclerosis, and synovial proliferation. Here, we describe the generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig) of the IgG1/k subtype that specifically and potently neutralizes IL-1α and IL-1β. In ABT-981, the IL-1β variable domain resides in the outer domain of the DVD-Ig, whereas the IL-1α variable domain is located in the inner position. ABT-981 specifically binds to IL-1α and IL-1β, and is physically capable of binding 2 human IL-1α and 2 human IL-1β molecules simultaneously. Single-dose intravenous and subcutaneous pharmacokinetics studies indicate that ABT-981 has a half-life of 8.0 to 10.4 d in cynomolgus monkey and 10.0 to 20.3 d in rodents. ABT-981 exhibits suitable drug-like-properties including affinity, potency, specificity, half-life, and stability for evaluation in human clinical trials. ABT-981 offers an exciting new approach for the treatment of OA, potentially addressing both disease modification and symptom relief as a disease-modifying OA drug. PMID:25764208

  14. Impact of short range hydrophobic interactions and long range electrostatic forces on the aggregation kinetics of a monoclonal antibody and a dual-variable domain immunoglobulin at low and high concentrations.

    PubMed

    Kumar, Vineet; Dixit, Nitin; Zhou, Liqiang Lisa; Fraunhofer, Wolfgang

    2011-12-12

    The purpose of this work was to determine the nature of long and short-range forces governing protein aggregation kinetics at low and high concentrations for a monoclonal antibody (IgG1) and a dual-variable-domain immunoglobulin (DVD-Ig). Protein-protein interactions (PPI) were studied under dilute conditions by utilizing the methods of static (B(22)) and dynamic light scattering (k(D)). PPI in solutions containing minimal ionic strengths were characterized to get detailed insights into the impact of ionic strength on aggregation. Microcalorimetry and susceptibility to denature at air-liquid interface were used to assess the tertiary structure and quiescent stability studies were conducted to study aggregation characteristics. Results for IgG1 showed that electrostatic interactions governed protein aggregation kinetics both under dilute and concentrated conditions (i.e., 5 mg/mL and 150 mg/mL). For DVD-Ig molecules, on the other hand, although electrostatic interactions governed protein aggregation under dilute conditions, hydrophobic forces clearly determined the kinetics at high concentrations. This manuscript shows for the first time that short-range hydrophobic interactions can outweigh electrostatic forces and play an important role in determining protein aggregation at high concentrations. Additionally, results show that although higher-order virial coefficients become significant under low ionic strength conditions, removal of added charges may be used to enhance the aggregation stability of dilute protein formulations.

  15. [Avidity of polyreactive immunoglobulins].

    PubMed

    Bobrovnik, S A

    2014-01-01

    An analysis of the mechanism of interaction between polyreactive immunoglobulins (PRIG) and antigen was conducted and it was shown that most of the traditional methods of antibody affinity evaluation are not applicable for PRIG affinity. The comparative assessment of the mouse and human PRIG avidity against ovalbumin and horse myoglobin and the avidity of specific monoclonal antibodies against ovalbumin have shown that the avidity of PRIG not only is much less than the avidity of monoclonal antibodies but even exceeds it.

  16. Immunoglobulin genes of the turtles.

    PubMed

    Magadán-Mompó, Susana; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2013-03-01

    The availability of reptile genomes for the use of the scientific community is an exceptional opportunity to study the evolution of immunoglobulin genes. The genome of Chrysemys picta bellii and Pelodiscus sinensis is the first one that has been reported for turtles. The scanning for immunoglobulin genes resulted in the presence of a complex locus for the immunoglobulin heavy chain (IGH). This IGH locus in both turtles contains genes for 13 isotypes in C. picta bellii and 17 in P. sinensis. These correspond with one immunoglobulin M, one immunoglobulin D, several immunoglobulins Y (six in C. picta bellii and eight in P. sinensis), and several immunoglobulins that are similar to immunoglobulin D2 (five in C. picta belli and seven in P. sinensis) that was previously described in Eublepharis macularius. It is worthy to note that IGHD2 are placed in an inverted transcriptional orientation and present sequences for two immunoglobulin domains that are similar to bird IgA domains. Furthermore, its phylogenetic analysis allows us to consider about the presence of IGHA gene in a primitive reptile, so we would be dealing with the memory of the gene that originated from the bird IGHA. In summary, we provide a clear picture of the immunoglobulins present in a turtle, whose analysis supports the idea that turtles emerged from the evolutionary line from the differentiation of birds and the presence of the IGHA gene present in a common ancestor.

  17. Cloning and expression in Escherichia coli of a human gelatinase B-inhibitory single-chain immunoglobulin variable fragment (scFv).

    PubMed

    Zhou, N; Paemen, L; Opdenakker, G; Froyen, G

    1997-09-15

    The murine monoclonal antibody REGA-3G12 selectively and specifically inhibits the activity of human gelatinase B. The cDNA fragments which encode the variable regions of the light and heavy chains were isolated by PCR-mediated cloning and sequenced. Single-chain Fv expression constructs for Escherichia coli were generated in which c-myc tag sequences were encoded. Inducible expression of the scFv and secretion to the periplasm were obtained with higher yields when the c-myc tag sequence was positioned at the amino-terminal side. The inhibitory activity of purified scFv on neutrophil gelatinase B was tested in a gelatin degradation assay and it was found to possess a similar specific activity as that of the intact monoclonal antibody and of the pepsin-clipped F(ab')2 derivative. This shows for the first time that inhibition of soluble enzymes with scFv is possible and opens new perspectives for the treatment of diseases with excessive and detrimental enzyme production in the host.

  18. Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice

    PubMed Central

    Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W.; Rapoport, Basil

    2014-01-01

    Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

  19. Biology of Immunoglobulins

    PubMed Central

    Berlot, Giorgio; Rossini, Perla; Turchet, Federica

    2015-01-01

    Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis in adult patients, in whom the current guidelines even recommend against their use, despite that many studies demonstrated either their beneficial effects in different subsets of patients and that some preparations of IvIg are more effective than other. The biology of Ig are reviewed, aiming to a more in-depth understanding of their properties in order to clarify their possible indications in different clinical settings. PMID:25674545

  20. Immunoglobulin profile in schizophrenia.

    PubMed

    Bhatia, M S; Dhar, N K; Agrawal, P; Khurana, S K; Neena, B; Malik, S C

    1992-08-01

    The present study was conducted on 40 new consecutive schizophrenic patients admitted in the psychiatry ward. The diagnosis of schizophrenia was done by Research Diagnosis Criteria (RDC). Serum immunoglobulins were were estimated in schizophrenic patients and were age and sex matched with 40 healthy individuals, comprising the control group. The IgG and IgA mean levels of schizophrenic patients were found to be significantly higher (p < 0.01) than the normal healthy individuals. There were however no significant differences between the schizophrenic patients and control group regarding total proteins, albumin and globulin levels. In subtypes of schinophrenia based on phenomenology only, paranoid group scored significantly higher (p < 0.01) IgG and IgA mean values than other types of Schizophrenia (catatonic, disorganised and undifferentiated).

  1. Immunoglobulin Resistance in Kawasaki Disease

    PubMed Central

    Hartas, Georgios A.; Hashmi, Syed Shahrukh; Pham-Peyton, Chi; Tsounias, Emmanouil; Bricker, John T.

    2015-01-01

    Background: The aim of this study was to identify risk factors for immunoglobulin resistance, including clinical symptoms such as arthritis and the pH of intravenous immunoglobulin. Methods: The data of children with Kawasaki disease who had received immunoglobulin were evaluated. Data regarding the brand of immunoglobulin administered were abstracted from the pharmacy records. Results: Eighty consecutive children with Kawasaki disease were evaluated (Mdnage=28 months, 66% male). The prevalence of immunoglobulin resistance was 30%. Arthritis was a presenting symptom in the acute phase of Kawasaki disease in 8% (6/80, all male) and was seen in significant association with immunoglobulin resistance in comparison to those without arthritis (16.7% vs. 0.2%, p=0.008). Next, the immunoglobulin brand types were divided into two groups: the relatively high pH group (n=16), including Carimune (pH 6.6±0.2), and the low pH group (n=63), including Gamunex (pH 4–4.5) or Privigen (pH 4.6–5). Overall, no significant difference in immunoglobulin responsiveness was found between the low pH and the high pH groups (73% vs. 56%, p=0.193), although the low pH group showed a trend toward a larger decrease in erythrocyte sedimentation rate (p=0.048), lower steroid use (p=0.054), and lower coronary involvement (p=0.08) than those in the high pH group. Conclusions: Children presenting with arthritis in the acute phase of Kawasaki disease may be at risk for immunoglobulin resistance. PMID:25852966

  2. Immunoglobulin double-isotype expression by trans-mRNA in a human immunoglobulin transgenic mouse.

    PubMed Central

    Shimizu, A; Nussenzweig, M C; Mizuta, T R; Leder, P; Honjo, T

    1989-01-01

    We have studied immunoglobulin double-isotype expression in a transgenic mouse (TG.SA) in which expression of the endogenous immunoglobulin heavy chain locus is almost completely excluded by a nonallelic rearranged human mu transgene. By flow-cytometric analyses, we have shown that a small, but significant, portion (about 4%) of transgenic spleen cells expresses human mu (transgene) and mouse gamma (endogenous) chains when cultured in vitro with bacterial lipopolysaccharide and interleukin 4. By using amplification of cDNA by the polymerase chain reaction, followed by cloning and sequencing of the amplified cDNA fragment, we have demonstrated expression of trans-mRNA consisting of the transgenic variable and endogenous constant (gamma 1) region sequences. Such trans-mRNA could be produced by either switch recombination or trans-splicing between the transgene and endogenous sterile gamma 1-gene transcripts. These results indicate that trans-splicing might be a possible mechanism for the immunoglobulin double-isotype expression in normal B lymphocytes that have not rearranged the second expressed constant region gene. Images PMID:2510157

  3. Immunoglobulin K light chain deficiency: A rare, but probably underestimated, humoral immune defect.

    PubMed

    Sala, Pierguido; Colatutto, Antonio; Fabbro, Dora; Mariuzzi, Laura; Marzinotto, Stefania; Toffoletto, Barbara; Perosa, Anna R; Damante, Giuseppe

    2016-04-01

    Human immunoglobulin molecules are generated by a pair of identical heavy chains, which identify the immunoglobulin class, and a pair of identical light chains, Kappa or Lambda alternatively, which characterize the immunoglobulin type. In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound. Very few cases of immunoglobulin Kappa or Lambda light chain defects have been reported. Furthermore, the genetic basis of this defect has been extensively explored only in a single case. We report a case of a patient suffering of serious recurrent bacterial infections, which was caused by a very rare form of immunoglobulin disorder, consisting of a pure defect of Kappa light chain. We evaluated major serum immunoglobulin concentrations, as well as total and free Kappa and Lambda light chain concentrations. Lymphocyte phenotyping was also performed and finally we tested the Kappa chain VJ rearrangement as well as the constant Kappa region sequence. Studies performed on VJ rearrangement showed a polyclonal genetic arrangement, whereas the gene sequencing for the constant region of Kappa chain showed a homozygous T to G substitution at the position 1288 (rs200765148). This mutation causes a substitution from Cys to Gly in the protein sequence and, therefore, determines the abnormal folding of the constant region of Kappa chain. We suggest that this defect could lead to an effective reduction of the variability of total antibody repertoire and a consequent defect of an apparently normal immunoglobulin response to common antigens.

  4. Aggregates, Crystals, Gels, and Amyloids: Intracellular and Extracellular Phenotypes at the Crossroads of Immunoglobulin Physicochemical Property and Cell Physiology

    PubMed Central

    2013-01-01

    Recombinant immunoglobulins comprise an important class of human therapeutics. Although specific immunoglobulins can be purposefully raised against desired antigen targets by various methods, identifying an immunoglobulin clone that simultaneously possesses potent therapeutic activities and desirable manufacturing-related attributes often turns out to be challenging. The variable domains of individual immunoglobulins primarily define the unique antigen specificities and binding affinities inherent to each clone. The primary sequence of the variable domains also specifies the unique physicochemical properties that modulate various aspects of individual immunoglobulin life cycle, starting from the biosynthetic steps in the endoplasmic reticulum, secretory pathway trafficking, secretion, and the fate in the extracellular space and in the endosome-lysosome system. Because of the diverse repertoire of immunoglobulin physicochemical properties, some immunoglobulin clones' intrinsic properties may manifest as intriguing cellular phenotypes, unusual solution behaviors, and serious pathologic outcomes that are of scientific and clinical importance. To gain renewed insights into identifying manufacturable therapeutic antibodies, this paper catalogs important intracellular and extracellular phenotypes induced by various subsets of immunoglobulin clones occupying different niches of diverse physicochemical repertoire space. Both intrinsic and extrinsic factors that make certain immunoglobulin clones desirable or undesirable for large-scale manufacturing and therapeutic use are summarized. PMID:23533417

  5. Molecular analysis of the immunoglobulin genes in goose.

    PubMed

    Huang, Tian; Wu, Kun; Yuan, Xiaoli; Shao, Shuai; Wang, WenYuan; Wei, Si; Cao, Gengsheng

    2016-07-01

    Immunoglobulins play an important role in adaptive immune system as defense molecules against pathogens. However, our knowledge on avian immunoglobulin genes has been limited to a few species. In this study, we analyzed goose (Anser cygnoides orientalis) immunoglobulin genes. Three IgH classes including IgM, IgA, IgY and λ light chain were identified. The IgM and IgA heavy chain constant regions are characteristically similar to their counterparts described in other vertebrates. In addition to the classic Ig isotypes, we also detected a transcript that encoded a truncated form of IgY (IgY(ΔFc)) in goose. Similar to duck, the IgY(ΔFc) in goose was generated by using different transcriptional termination signal of the same υ gene. Limited variability and only one leader peptide were observed in VH and VL domains, which suggested that gene conversion was the primary mechanism involved in goose antibody diversity. Our study provides more insights into the immunoglobulin genes in goose that had not been fully explored before.

  6. Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency

    PubMed Central

    Niebur, H B; Duff, C M; Shear, G F; Nguyen, D; Alberdi, T K; Dorsey, M J; Sleasman, J W

    2015-01-01

    Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin®) was compared with 20% SCIG (Hizentra®) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2–75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin. PMID:25761372

  7. Efficacy and tolerability of 16% subcutaneous immunoglobulin compared with 20% subcutaneous immunoglobulin in primary antibody deficiency.

    PubMed

    Niebur, H B; Duff, C M; Shear, G F; Nguyen, D; Alberdi, T K; Dorsey, M J; Sleasman, J W

    2015-09-01

    Multiple subcutaneous immunoglobulin (SCIG) products are available to treat primary antibody deficiency (PAD). The efficacy and tolerability of 16% SCIG (Vivaglobin(®) ) was compared with 20% SCIG (Hizentra(®) ) in PAD subjects. The study was a prospective, single-centre, open-label study of PAD subjects transitioning Vivaglobin to equivalent Hizentra doses, rounded to the nearest vial size. Comparisons included immunoglobulin (Ig)G levels; tetanus, varicella and Streptococcus pneumoniae titres; adverse events (AEs), annual infection rate and quality of life during 8 weeks of Vivaglobin and 24 weeks of Hizentra. Thirty-two subjects (aged 2-75 years) participated. Rounding to the nearest Hizentra vial size resulted in a 12·8% (± 2·9%) increase in SCIG dose. Median immunoglobulin (Ig)G level following 8 weeks of Vivaglobin was similar to 24 weeks of Hizentra (1050 versus 1035 mg/dl, respectively; P = 0·77). Both products had similar protective titres to tetanus, varicella and serotypes of S. pneumoniae, which were variable but well above protective levels. After 12 weeks of Hizentra, subjects reported fewer local site reactions compared with Vivaglobin. Switching products resulted in increased systemic AEs in some subjects but, overall, not significantly higher than during Vivaglobin treatment. Average infusion time decreased from 104·7 min (3·3 sites) with Vivaglobin to 70·7 min (2·2 sites) with Hizentra (P = 0·0005). Acute serious bacterial infections were similar. Treatment satisfaction was superior with Hizentra. Hizentra and Vivaglobin have similar pharmacokinetics and efficacy. Although transition to a different SCIG product initially increased AEs, Hizentra is well tolerated and can be infused more rapidly and with fewer sites compared to Vivaglobin.

  8. Comparative analyses of immunoglobulin genes: surprises and portents.

    PubMed

    Flajnik, Martin F

    2002-09-01

    The study of immunoglobulin genes in non-mouse and non-human models has shown that different vertebrate groups have evolved distinct methods of generating antibody diversity. By contrast, the development of T cells in the thymus is quite similar in all of the species that have been examined. The three mechanisms by which B cells uniquely modify their immunoglobulin genes -- somatic hypermutation, gene conversion and class switching -- are increasingly believed to share some fundamental mechanisms, which studies in different vertebrate groups have helped (and will continue to help) to resolve. When these mechanisms are better understood, we should be able to look to the constitutive pathways from which they have evolved and perhaps determine whether the rearrangement of variable, diversity and joining antibody gene segments -- V(D)J recombination -- was superimposed on an existing adaptive immune system.

  9. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation.

    PubMed

    Peters, A; Storb, U

    1996-01-01

    To identify DNA sequences that target the somatic hypermutation process, the immunoglobulin gene promoter located upstream of the variable (V) region was duplicated upstream of the constant (C) region of a kappa transgene. Normally, kappa genes are somatically mutated only in the VJ region, but not in the C region. In B cell hybridomas from mice with this kappa transgene (P5'C), both the VJ region and the C region, but not the region between them, were mutated at similar frequencies, suggesting that the mutation mechanism is related to transcription. The downstream promoter was not occluded by transcripts from the upstream promoter. In fact, the levels of transcripts originating from the two promoters were similar, supporting a mutation model based on initiation of transcripts. Several "hot-spots" of somatic mutation were noted, further demonstrating that this transgene has the hallmarks of somatic mutation of endogenous immunoglobulin genes. A model linking somatic mutation to transcription-coupled DNA repair is proposed.

  10. Studies of heat precipitable immunoglobulins

    PubMed Central

    Patterson, R.; Roberts, Mary; Pruzansky, J. J.

    1970-01-01

    The nature of the heat precipitation of 3 mononoclonal heat labile immunoglobulins was studied. These included 2 γG pyroglobulins and one γM pyroglobulin. Thermoprecipitable activity of both γG pyroglobulins could be localized to their heavy chains and to the Fab fragments of one of them. Heat precipitability of the γM paraprotein required the presence of the intact γM molecule since 7S subunits did not precipitate. The thermal precipitates appeared to result from intramolecular or intermolecular reactions with the formation of strong covalent bonds rather than weak non-covalent bonds. The importance of disulphide bonding was excluded in the precipitation of both γG but not in the γM pyroglobulins. Heat precipitation of the monoclonal γM resulted in coprecipitation of other proteins, particularly γG globulin, which suggested a specific type of reaction with this immunoglobulin. The interaction of the γM pyroglobulin, normal γG and heat produced an irreversible precipitate. ImagesFig. 1 PMID:4099668

  11. Epstein-Barr virus infection in vitro can rescue germinal center B cells with inactivated immunoglobulin genes.

    PubMed

    Chaganti, Sridhar; Bell, Andrew I; Pastor, Noelia Begue; Milner, Anne E; Drayson, Mark; Gordon, John; Rickinson, Alan B

    2005-12-15

    Immunoglobulin genotyping of Epstein-Barr virus (EBV)-positive posttransplantation lymphoproliferative disease has suggested that such lesions often arise from atypical post-germinal center B cells, in some cases carrying functionally inactivated immunoglobulin genes. To investigate whether EBV can rescue cells that are failed products of the somatic hypermutation process occurring in germinal centers (GCs), we isolated GC cells from tonsillar cell suspensions and exposed them to EBV in vitro. Screening more than 100 EBV-transformed cell lines of GC origin identified 6 lines lacking surface immunoglobulin, a phenotype never seen among lines derived from circulating naive or memory B cells. Furthermore, 3 of the 6 surface immunoglobulin-negative GC lines carried inactivating mutations in the immunoglobulin H (IgH) variable gene sequence. The ability of EBV to rescue aberrant products of the germinal center reaction in vitro strengthens the probability that a parallel activity contributes to EBV's lymphomagenic potential in vivo.

  12. Atypical immunoglobulin light chain amyloidosis

    PubMed Central

    Wu, Xia; Feng, Jun; Cao, Xinxin; Zhang, Lu; Zhou, Daobin; Li, Jian

    2016-01-01

    Abstract Background: Primary immunoglobulin light chain amyloidosis (AL amyloidosis) is a plasma cell disorder which mainly affects heart, kidneys, liver, and peripheral nervous system. Cases of atypical AL amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported, and data about the management and clinical outcomes of the patients are scarce. Methods: Herein, we present 3 new cases of AL amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature. Results: Moreover, we observed overrepresentations of liver involvement and bone marrow involvement in AL amyloidosis with spontaneous vertebral compression fracture. Conclusion: We believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of AL amyloidosis can facilitate earlier diagnosis and earlier treatment. PMID:27603350

  13. Renal AH Amyloidosis Associated With a Truncated Immunoglobulin Heavy Chain Undetectable by Immunostaining.

    PubMed

    Manabe, Shun; Hatano, Michiyasu; Yazaki, Masahide; Nitta, Kosaku; Nagata, Michio

    2015-12-01

    AH amyloidosis is a rare type of amyloidosis caused by deposition of monoclonal immunoglobulin heavy chain. The key diagnostic feature is positive immunostaining for a single class of immunoglobulin heavy chain. We report a case of AH amyloidosis with immunoglobulin G (IgG) λ monoclonal gammopathy that was diagnosed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) after immunostaining of renal tissue for immunoglobulin heavy chain gave negative results. The molecular weight of the purified renal amyloid protein was ∼11kDa, which was determined by LC-MS/MS analysis to correspond to an amino acid sequence comprising the variable region and a truncated portion of the constant region of IgG heavy chain. The exact same truncated heavy chain was detected by LC-MS/MS of a protein isolated from the patient's serum, suggesting that the truncated serum protein was the precursor of the amyloid protein. Because antibodies to immunoglobulin heavy chain recognize the Fc portion, the large deletion in the constant region could explain the negative results upon immunostaining. Direct protein detection by LC-MS/MS is a powerful aid to diagnose renal AH amyloidosis, particularly when the findings of immunoglobulin staining are inconsistent with the background monoclonal gammopathy.

  14. Somatic hypermutation of immunoglobulin genes is independent of the Bloom's syndrome DNA helicase.

    PubMed

    Sack, S Z; Liu, Y; German, J; Green, N S

    1998-05-01

    Immunoglobulin gene somatic mutation leads to antibody affinity maturation through the introduction of multiple point mutations in the antigen binding site. No genes have as yet been identified that participate in this process. Bloom's syndrome (BS) is a chromosomal breakage disorder with a mutator phenotype. Most affected individuals exhibit an immunodeficiency of undetermined aetiology. The gene for this disorder, BLM, has recently been identified as a DNA helicase. If this gene were to play a role in immunoglobulin mutation, then people with BS may lack normally mutated antibodies. Since germ-line, non-mutated immunoglobulin genes generally produce low affinity antibodies, impaired helicase activity might be manifested as the immunodeficiency found in BS. Therefore, we asked whether BLM is specifically involved in immunoglobulin hypermutation. Sequences of immunoglobulin variable (V) regions were analysed from small unsorted blood samples obtained from BS individuals and compared with germ-line sequences. BS V regions displayed the normal distribution of mutations, indicating that the defect in BS is not related to the mechanism of somatic mutation. These data strongly argue against BLM being involved in this process. The genetic approach to identifying the genes involved in immunoglobulin mutation will require further studies of DNA repair- and immunodeficient individuals.

  15. Perspectives on Immunoglobulins in Colostrum and Milk

    PubMed Central

    Hurley, Walter L.; Theil, Peter K.

    2011-01-01

    Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk. PMID:22254105

  16. PHYLOGENY OF IMMUNOGLOBULIN STRUCTURE AND FUNCTION

    PubMed Central

    Clem, L. W.; Small, P. A.

    1967-01-01

    Lemon sharks immunized with bovine serum albumin produced two molecular forms of antibodies detectable by passive hemagglutination of antigen-coated, tanned sheep erythrocytes. Throughout the course of immunization 2-ME-sensitive antibody was associated with a 19S immunoglobulin fraction (4–5 mg/ml serum) while late in the course of immunization antibody was found also associated with a 7S immunoglobulin fraction (7–8 mg/ml serum). No evidence for any anamnestic response was found in these animals. Naturally occurring hemagglutinins for sheep erythrocytes were found to be 2-ME-sensitive and present in the 19S immunoglobulin fraction. These immunoglobulin fractions were readily purified by DEAE-cellulose chromatography and Sephadex G-200 gel filtration. Both immunoglobulin molecules yielded equimolar amounts of H and L polypeptide chains when subjected to extensive reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. Antigenically reactive H and L chains were obtained by partial reduction and alkylation followed by gel filtration in 1 M propionic acid. The 7S and 19S immunoglobulin H chains were indistinguishable by fingerprints of tryptic digests, disc electrophoretic patterns, antigenic properties, and mass (molecular weight ∼70,000), thus suggesting these two molecules to belong to the same immunoglobulin class. The shark 19S and 7S immunoglobulin L chains were indistinguishable from each other by similar criteria and were different from the H chains. These L chains exhibited the electrophoretic heterogeneity of their mammalian counterparts. The 7S (shark immunoglobulin) molecule was shown to have a molecular weight of ∼160,000 and to consist of 2H and 2L polypeptide chains (total mass ≅180,000). The 19S molecule was shown to have a molecular weight of 800,000–900,000; therefore, there were probably five 7S subunits per 19S molecule, comparable to mammalian γM. Other reasons for considering the 7S and the 19S lemon shark

  17. Shared epitopes of avian immunoglobulin light chains.

    PubMed

    Benčina, Mateja; Cizelj, Ivanka; Berčič, Rebeka Lucijana; Narat, Mojca; Benčina, Dušan; Dovč, Peter

    2014-04-15

    Like all jawed vertebrates, birds (Aves) also produce antibodies i.e. immunoglobulins (Igs) as a defence mechanism against pathogens. Their Igs are composed of two identical heavy (H) and light (L) chains which are of lambda isotype. The L chain consists of variable (VL), joining (JL) and constant (CL) region. Using enzyme immunoassays (EIA) and two monoclonal antibodies (mAbs) (3C10 and CH31) to chicken L chain, we analysed their cross-reactivity with sera from 33 avian species belonging to nine different orders. Among Galliformes tested, mAbs 3C10 and CH31 reacted with L chains of chicken, turkey, four genera of pheasants, tragopan and peafowl, but not with sera of grey partridge, quail and Japanese quail. Immunoglobulins of guinea-fowl reacted only with mAb 3C10. Both mAbs reacted also with the L chain of Eurasian griffon (order Falconiformes) and domestic sparrow (order Passeriformes). Sera from six other orders of Aves did not react with either of the two mAbs. EIA using mAbs 3C10 and CH31 enabled detection of antibodies to major avian pathogens in sera of chickens, turkeys, pheasants, peafowl, Eurasian griffon and guinea-fowl (only with mAb 3C10). The N-terminal amino acid sequence of pheasant L chain (19 residues) was identical to that of chicken. Sequences of genes encoding the L chain constant regions of pheasants, turkey and partridge were determined and deposited in the public database (GenBank accession numbers: FJ 649651, FJ 649652 and FJ 649653, respectively). Among them, amino acid sequence of pheasants is the most similar to that of chicken (97% similarity), whereas those of turkey and partridge have greater similarity to each other (89%) than to any other avian L chain sequence. The characteristic deletion of two amino acids which is present in the L chain constant region in Galliformes has been most likely introduced to their L chain after their divergence from Anseriformes.

  18. Shared epitopes of avian immunoglobulin light chains.

    PubMed

    Benčina, Mateja; Cizelj, Ivanka; Berčič, Rebeka Lucijana; Narat, Mojca; Benčina, Dušan; Dovč, Peter

    2014-04-15

    Like all jawed vertebrates, birds (Aves) also produce antibodies i.e. immunoglobulins (Igs) as a defence mechanism against pathogens. Their Igs are composed of two identical heavy (H) and light (L) chains which are of lambda isotype. The L chain consists of variable (VL), joining (JL) and constant (CL) region. Using enzyme immunoassays (EIA) and two monoclonal antibodies (mAbs) (3C10 and CH31) to chicken L chain, we analysed their cross-reactivity with sera from 33 avian species belonging to nine different orders. Among Galliformes tested, mAbs 3C10 and CH31 reacted with L chains of chicken, turkey, four genera of pheasants, tragopan and peafowl, but not with sera of grey partridge, quail and Japanese quail. Immunoglobulins of guinea-fowl reacted only with mAb 3C10. Both mAbs reacted also with the L chain of Eurasian griffon (order Falconiformes) and domestic sparrow (order Passeriformes). Sera from six other orders of Aves did not react with either of the two mAbs. EIA using mAbs 3C10 and CH31 enabled detection of antibodies to major avian pathogens in sera of chickens, turkeys, pheasants, peafowl, Eurasian griffon and guinea-fowl (only with mAb 3C10). The N-terminal amino acid sequence of pheasant L chain (19 residues) was identical to that of chicken. Sequences of genes encoding the L chain constant regions of pheasants, turkey and partridge were determined and deposited in the public database (GenBank accession numbers: FJ 649651, FJ 649652 and FJ 649653, respectively). Among them, amino acid sequence of pheasants is the most similar to that of chicken (97% similarity), whereas those of turkey and partridge have greater similarity to each other (89%) than to any other avian L chain sequence. The characteristic deletion of two amino acids which is present in the L chain constant region in Galliformes has been most likely introduced to their L chain after their divergence from Anseriformes. PMID:24603015

  19. Cytomegalovirus Immunoglobulin After Thoracic Transplantation

    PubMed Central

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-01-01

    Abstract Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R−). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation. PMID:26900989

  20. Immunoglobulin gene diversification in cattle.

    PubMed

    Meyer, A; Parng, C L; Hansal, S A; Osborne, B A; Goldsby, R A

    1997-01-01

    Research in several species has revealed that different types of mammals have evolved divergent molecular and cellular strategies for generating immunoglobulin diversity. Other chapters in this text have highlighted the specific characteristics unique to chicken, rabbit, mouse, human and sheep B lymphocyte development; namely indicating differences in the mechanisms of diversity and the site of primary B cell development. Studies of the bovine system have indicated that like the sheep system, the ileal Peyer's patch (IPP) is a likely chicken bursal equivalent, and is a site of primary B lymphocyte development. Substantial investigation in sheep has indicated that Ig diversity is created by untemplated somatic mutation and intense selective pressure (Reynaud et al., 1991). The frequency of alteration in the sheep Ig light chain gene locus also is characteristic of the bovine system, however, recent evidence from sequencing of bovine lambda light chain genes indicates that one mechanism that contributes to diversity is gene conversion, utilizing several pseudogenes located in the Ig locus (Parng et al., 1996). The mechanism by which this hyperalteration of Ig genes occurs in both sheep and cattle is poorly understood and is thus the focus of considerable investigation. The study of events in the IPP may also have informative ramifications for secondary diversification of the Ig repertoire by somatic hyperalteration in germinal centers.

  1. Mapping of Heavy Chain Genes for Mouse Immunoglobulins M and D

    NASA Astrophysics Data System (ADS)

    Liu, Chih-Ping; Tucker, Philip W.; Mushinski, J. Frederic; Blattner, Frederick R.

    1980-09-01

    A single DNA fragment containing both μ and δ immunoglobulin heavy chain genes has been cloned from normal BALB/c mouse liver DNA with a new λ phage vector Charon 28. The physical distance between the membrane terminal exon of μ and the first domain of δ is 2466 base pairs, with δ on the 3' side of μ . A single transcript could contain a variable region and both μ and δ constant regions. The dual expression of immunoglobulins M and D on spleen B cells may be due to alternate splicing of this transcript.

  2. Cloning and sequencing of human lambda immunoglobulin genes by the polymerase chain reaction.

    PubMed

    Songsivilai, S; Bye, J M; Marks, J D; Hughes-Jones, N C

    1990-12-01

    Universal oligonucleotide primers, designed for amplifying and sequencing genes encoding the rearranged human lambda immunoglobulin variable region, were validated by amplification of the lambda light chain genes from four human heterohybridoma cell lines and in the generation of a cDNA library of human V lambda sequences from Epstein-Barr virus-transformed human peripheral blood lymphocytes. This technique allows rapid cloning and sequencing of human immunoglobulin genes, and has potential applications in the rescue of unstable human antibody-producing cell lines and in the production of human monoclonal antibodies.

  3. Immunoglobulin genes implicated in glioma risk.

    PubMed

    Pandey, Janardan P; Kaur, Navtej; Costa, Sandra; Amorim, Julia; Nabico, Rui; Linhares, Paulo; Vaz, Rui; Viana-Pereira, Marta; Reis, Rui M

    2014-01-01

    Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus.

  4. Somatic hypermutations in the immunoglobulin genes of two new human lymphoma lines of lymphatic follicle origin.

    PubMed

    Wu, H Y; Tuomikoski, T; Eray, M; Mattila, P; Knuutila, S; Kaartinen, M

    1994-03-01

    Variable immunoglobulin heavy-chain regions (VDJ) of two newly established human lymphoma cell lines (HF-1 and HF-4) were sequenced. The most homologous germline VH gene found for both the HF-1 and HF-4 sequences was VH26 of the VH3a (V gene) family (82% and 91% homologies, respectively). The JH region of the HF-4 heavy-chain sequence contained two nucleotide differences compared to the published germline JH3 gene. The DHJH region of the HF-1 gene had a record high number (20%) of somatic mutations. The numerous hypermutations found in the HF-1 cell line support the hypothesis that in some human follicular lymphomas, mutations continue to accumulate in immunoglobulin genes during the malignant growth. Follicular lymphoma cell lines, which have an active mutational machinery, in future may help to solve the molecular events behind the somatic hypermutations modifying immunoglobulin genes of B lymphocytes.

  5. Immunoglobulin isotypes in childhood asthma.

    PubMed

    Najam, F I; Giasuddin, A S; Shembesh, A H

    1999-01-01

    Immunoglobulin isotypes (IgG, IgA, IgM, IgD, IgE) in serum were investigated in 64 Libyan children with mild to moderately severe asthma (age: 1-12 years; sex: 39 males, 25 females) (Group A) and in 57 healthy Libyan children (age: 1-12 years; sex: 30 males, 27 females (Group B). The patients were classified according to age into three groups (A1: 1-3 years; A2: > 3-5 years; A3: > 5-12 years); according to disease activity into two groups (AA: active disease; NA: inactive disease); and according to age plus disease activity into six groups (AA1, NA1; AA2, NA2; AA3, NA3). The healthy children were also divided according to age into three groups (B1: 1-3 years; B2: > 3-5 years; B3: > 5-12 years). IgG, IgA, IgM and IgD were measured by radial immunodiffusion method and IgE was estimated by enzyme immunoassay technique utilizing immunokits from bioMerieux, France. Serum levels of IgG, IgD and IgE were elevated significantly in patients compared to controls (A vs B: p < 0.05) while IgA and IgM levels were normal (p > 0.05). IgG and IgD levels were raised in A3 (p < 0.05), while IgD levels were raised in both A2 and A3 (p < 0.05) and IgE was elevated in all age groups (p < 0.05). However, IgG was elevated significantly in AA only, while IgD and IgE levels were high in both AA and NA (p < 0.05) and IgE was even considerably higher in AA compared to NA (p < 0.02). Further elevated levels were observed for IgG in AA3 only (p < 0.05), for IgD in NA2 (p < 0.01), AA3 (p < 0.01) and NA3 (p < 0.05) and IgE was much higher in patients with active disease than with inactive disease in all age groups (p < 0.05). The fact that asthmatic attack in majority of our patients can be explained as mediated through IgE and the possibilities that IgG and IgD may play roles as aetiopathogenetic or protective regulatory factors in childhood asthma are discussed.

  6. Rearrangements of immunoglobulin genes during differentiation and evolution.

    PubMed

    Honjo, T; Nakai, S; Nishida, Y; Kataoka, T; Yamawaki-Kataoka, Y; Takahashi, N; Obata, M; Shimizu, A; Yaoita, Y; Nikaido, T; Ishida, N

    1981-01-01

    Immunoglobulin genes are shown to undergo dynamic rearrangements during differentiation as well as evolution. We have demonstrated that a complete immunoglobulin heavy chain gene is formed by at least two types of DNA rearrangement during B cell differentiation. The first type of rearrangement is V-D-J recombination to complete a variable region sequence and the second type is S-S recombination to switch a constant region sequence. Both types of recombination are accompanied by deletion of the intervening DNA segment. Structure and organization of CH genes are elucidated by molecular cloning and nucleotide sequence determination. Organization of H chain genes is summarized as VH-(unknown distance)-JH-(6.5 kb)-C mu-(4.5 kb)-C delta-(unknown distance)-C gamma 3-(34 kb)-C gamma 1-(21 kb)-C gamma 2b-(15 kb)-C gamma 2a-(14.5 kb)-C epsilon-(12.5 kb)-C alpha. The S-S recombination takes place at the S region which is located at the 5' side of each CH gene. Nucleotide sequence of the S region comprises tandem repetition of closely related sequences. The S-S recombination seems to be mediated by short common sequences shared among S regions. A sister chromatid exchange model was proposed as a mechanism for S-S recombination. Comparison of nucleotide sequences of CH genes indicates that immunoglobulin genes have scrambled by intervening sequence-mediated domain transfer during their evolution.

  7. Switch Transcripts in Immunoglobulin Class Switching

    NASA Astrophysics Data System (ADS)

    Lorenz, Matthias; Jung, Steffen; Radbruch, Andreas

    1995-03-01

    B cells can exchange gene segments for the constant region of the immunoglobulin heavy chain, altering the class and effector function of the antibodies that they produce. Class switching is directed to distinct classes by cytokines, which induce transcription of the targeted DNA sequences. These transcripts are processed, resulting in spliced "switch" transcripts. Switch recombination can be directed to immunoglobulin G1 (IgG1) by the heterologous human metallothionein II_A promoter in mutant mice. Induction of the structurally conserved, spliced switch transcripts is sufficient to target switch recombination to IgG1, whereas transcription alone is not.

  8. Rapid separation of immunoglobulin M from immunoglobulin G antibodies for reliable diagnosis of recent rubella infections.

    PubMed Central

    Frisch-Niggemeyer, W

    1975-01-01

    Chromatography on controlled pore glass was adapted for the separation of immunoglobulin M (IgM) and immunoglobulin G (IgG) rubella antibodies from 0.3-ml samples of human serum. An extremely sharp separation of IgM from IgG antibodies could be obtained within 40 min. Nonspecific inhibitors were removed before chromatography by precipitation with high-molecular-weight dextran sulfate, and the titer of rubella antibodies in the different classes of immunoglobulins were assayed with a modified hemagglutination inhibition technique. The combination of these methods is recommended for routine tests. It permits an accurate diagnosis of recent rubella infection within a few hours. PMID:1194404

  9. Phylogen of immunoglobulin structure and function. 3. Immunoglobulins of the chicken.

    PubMed

    Leslie, G A; Clem, L W

    1969-12-01

    Chicken 7.1S immunoglobulin was purified from whole chicken serum by DEAE-cellulose chromatography and Sephadex G-200 gel filtration. The macroglobulin was purified by a combination of salt precipitation and Sephadex G-200 gel filtration. Both immunoglobulin molecules yielded 75% heavy (H) chains and 25% light (L) chains when subjected to extensive reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. Antigenically reactive H and L chains were obtained by partial reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. The 7.1S and 16.7S immunoglobulin H chains were antigenically unrelated to each other, whereas the L chains were antigenically indistinguishable from one another. The 16.7S H chains were found to have a mass of approximately 70,000, and the 7.1S H chains had a mass of 67,500. The mass of the L chains was approximately 22,000. Sedimentation equilibrium studies of the 7.1S immunoglobulin molecule gave a mol wt of approximately 170,000 which is in good agreement with the 179,000 predicted on the basis of 2 H and 2 L polypeptide chains. The 16.7S molecule was shown to have a mol wt of approximately 890,000. A reductive subunit that has a mol wt of approximately 174,000 has been isolated from the 16.7S molecule. These values are consistent with the chicken macroglobulin having five subunits, each of which has 2 H and 2 L chains. The hexose contents of the chicken 7.1S and 16.7S immunoglobulins are 2.2% and 2.6%, respectively. The extinction coefficients of the 7.1S and 16.7S immunoglobulins were 13.18 +/- 0.04 and 12.72 +/- 0.77, respectively, when measured in 0.3 M KCl. Based upon physical-chemical and antigenic characteristics, the 16.7S immunoglobulin most closely resembles IgM of mammals. The 7.1S immunoglobulin definitely belongs to a different class than the 16,7S immunoglobulin, but it does not align itself very well with any of the mammalian immunoglobulins. We propose that this molecule be designated as Ig

  10. Application of Oxford classification, and overexpression of transforming growth factor-β1 and immunoglobulins in immunoglobulin A nephropathy: correlation with World Health Organization classification of immunoglobulin A nephropathy in a Chinese patient cohort.

    PubMed

    Meng, Hongxue; Zhang, Lei; E, Xiaoqiang; Ye, Fei; Li, Huining; Han, Changsong; Yamakawa, Mitsunori; Jin, Xiaoming

    2014-01-01

    Immunoglobulin A nephropathy (IgAN) is characterized by the qualitative abnormality of immunoglobulin A (IgA) in circulation and deposits of IgA in the renal mesangium. Transforming growth factor β1 (TGF-β1) plays a key role in fibrogenesis and the progression of renal damage. This study aimed to investigate the clinicopathologic data on IgAN in northeastern China and the presence of TGF-β1, total IgA, and secretory IgA in the glomeruli and sera, as well as changes in galactose-deficient IgA1 in the serum. We investigated the clinicopathologic data of 1050 cases of IgAN diagnosed in a single center over 13 years. We then assessed the concentrations of TGF-β1 and immunoglobulins in the serum of 100 patients with IgAN and 56 healthy control subjects by enzyme-linked immunosorbent assay, and investigated their presence in the glomeruli by immunofluorescence and reverse transcriptase-polymerase chain reaction. From our data, 76.17% of the IgAN cases belonged to classes I and II according to the World Health Organization classification, representing the early stage. Compared with other studies, we found significantly lower frequencies of segmental glomerulosclerosis (27.71%) but higher frequencies of endocapillary proliferation (50.67%), and a similar proportion of mesangial hypercellularity (68.48%) and tubular atrophy/interstitial fibrosis (moderate, 17.81%; severe, 1.52%) in the northeastern Chinese cohort. There was an increased presence of TGF-β1 and immunoglobulins in the serum and glomeruli of IgAN, which correlates with the progression of pathologic classification. The pathologic variables of the Oxford classification correlated significantly with the WHO classifications. TGF-β1 and immunoglobulins could be used as biomarkers of IgAN pathogenic mechanisms, acting as important adjuncts to the original Oxford Classification.

  11. Evaluation of serum immunoglobulin E levels in bronchial asthma

    PubMed Central

    Sandeep, Thirunavukkarasu; Roopakala, Mysore Subrahmanyam; Silvia, Chickballapur Rayappa Wilma Delphine; Chandrashekara, Srikantaiah; Rao, Mohan

    2010-01-01

    Background: Immunoglobulin E and associated cellular responses are responsible for allergic airway diseases. A hypersensitivity reaction initiated by immunologic mechanisms, mediated by IgE antibodies occurs in allergic asthma Aim: To estimate and compare serum IgE levels in mild, moderate, and severe asthmatics and in normal subjects and to obtain a mathematical model describing the relationship between serum IgE levels and severity of asthma. Materials and Methods: A stratified sample of 60 patients within age group of 18-60 years and 31 male and 29 female asthmatic patients and 13 healthy controls within 18-60 years were included in this study and classified according to GINA classification. Serum IgE levels were estimated by using ELISA kit. Results: Mean IgE levels ranged from 151.95 IU/ml in normal subjects to 1045.32 IU/ml in severe asthmatics. The model developed was 27% efficient. Conclusion: Serum Immunoglobulin E levels were high in asthmatics as compared to normal subjects. On an average, the levels increased as the severity of asthma increased. However, there was no statistically significant correlation since the variability in each level of asthma was very large PMID:20931031

  12. Polymerization of immunoglobulin domains: A model system for the development of facilitated macromolecular assembly

    SciTech Connect

    Stevens, F.J.; Myatt, E.A.

    1991-01-01

    We have recently determined that monoclonal immunoglobulin light chains (Bence Jones proteins) are capable of reversible polymerization at room temperature. This property, as exhibited by immunoglobulin light chains (normally a component of an intact antibody molecule), may have novel implications for the development of molecular nanotechnology.'' The polymerization capability of the immunoglobulin light chain is associated with the so-called variable domain of this molecule. The variable domain is a durable, compact beta-sheet structure of molecular weight approximately 12,000. Most of the primary sequence variation is limited to one portion of the molecule, that portion associated with the contribution of immunoglobulin light chains to the recognition and binding of thousand of different antigens by antibodies. As a consequence of these variations, different light chains polymerize with different degrees of avidity, from negligible to extensive. The polymerization process depends on solution parameters such as Ph. Thus, polymerization might be induced at one pH and suppressed or reversed at another. Combinations of molecules of appropriate specificities could assemble into structures of predetermined three-dimensional forms and properties. These features suggest that Bence Jones proteins represent a powerful model system within which to develop empirical rules relevant to a technology of protein-based construction''. Development of these rules will require the combined efforts of biophysical and crystallographic studies, protein engineering, and molecular modeling. 53 refs., 5 figs.

  13. Polymerization of immunoglobulin domains: A model system for the development of facilitated macromolecular assembly

    SciTech Connect

    Stevens, F.J.; Myatt, E.A.

    1991-12-31

    We have recently determined that monoclonal immunoglobulin light chains (Bence Jones proteins) are capable of reversible polymerization at room temperature. This property, as exhibited by immunoglobulin light chains (normally a component of an intact antibody molecule), may have novel implications for the development of ``molecular nanotechnology.`` The polymerization capability of the immunoglobulin light chain is associated with the so-called variable domain of this molecule. The variable domain is a durable, compact beta-sheet structure of molecular weight approximately 12,000. Most of the primary sequence variation is limited to one portion of the molecule, that portion associated with the contribution of immunoglobulin light chains to the recognition and binding of thousand of different antigens by antibodies. As a consequence of these variations, different light chains polymerize with different degrees of avidity, from negligible to extensive. The polymerization process depends on solution parameters such as Ph. Thus, polymerization might be induced at one pH and suppressed or reversed at another. Combinations of molecules of appropriate specificities could assemble into structures of predetermined three-dimensional forms and properties. These features suggest that Bence Jones proteins represent a powerful model system within which to develop empirical rules relevant to a technology of protein-based ``construction``. Development of these rules will require the combined efforts of biophysical and crystallographic studies, protein engineering, and molecular modeling. 53 refs., 5 figs.

  14. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins

    PubMed Central

    Mukerji, Shibani S.; Lam, Alice D.

    2016-01-01

    We report the case of a 68-year-old man from southeastern Massachusetts presenting with encephalitis due to eastern equine encephalitis (EEE) virus. Despite the high morbidity and mortality rate of EEE, the patient made a near complete recovery in the setting of receiving early intravenous immunoglobulins. PMID:26740855

  15. Explanatory style and Immunoglobulin A (IgA).

    PubMed

    Brennan, F X; Charnetski, C J

    2000-01-01

    The construct of explanatory style has been related to numerous aspects of human psychology, including health. Our research has focused on the effects of various psychological variables on the immune system, in particular Immunoglobulin A (IgA). We had participants fill out the Attributional Style Questionnaire (ASQ), the predominant measure of explanatory style, and assayed saliva samples for secretory IgA. No relationship was observed between overall ASQ score and IgA, or composite optimism score and IgA. However, we observed significant negative correlations between both the composite pessimism score and IgA, as well as the hopelessness score and IgA. Pessimistic explanatory style may therefore be related to immune system deficits and poor health. PMID:11330488

  16. Immunoglobulin genes and diversity: what we have learned from domestic animals.

    PubMed

    Sun, Yi; Liu, Zhancai; Ren, Liming; Wei, Zhiguo; Wang, Ping; Li, Ning; Zhao, Yaofeng

    2012-06-20

    This review focuses on the diversity of immunoglobulin (Ig) genes and Ig isotypes that are expressed in domestic animals. Four livestock species-cattle, sheep, pigs, and horses-express a full range of Ig heavy chains (IgHs), including μ, δ, γ, ϵ, and α. Two poultry species (chickens and ducks) express three IgH isotypes, μ, υ, and α, but not δ. The κ and λ light chains are both utilized in the four livestock species, but only the λ chain is expressed in poultry. V(D)J recombination, somatic hypermutation (SHM), and gene conversion (GC) are three distinct mechanisms by which immunoglobulin variable region diversity is generated. Different domestic animals may use distinct means to diversify rearranged variable regions of Ig genes.

  17. Chronic idiopathic thrombocytopenia treated with immunoglobulin.

    PubMed Central

    Mori, P G; Mancuso, G; del Principe, D; Duse, M; Miniero, R; Tovo, R; Bardare, M; Carnelli, V; de Mattia, D

    1983-01-01

    Twenty five children with chronic idiopathic thrombocytopenic purpura followed from 6-96 months in 7 Italian paediatric departments were treated with high dose immunoglobulin according to a multicentre protocol. Positive responses were observed in 20 of 25 patients (80%) and negative responses in 5 of 25 (20%). On previous steroid treatment 7 of 10 positive responders were steroid resistant and 13 of 15 were steroid dependent. Within four weeks of beginning treatment 16 of 20 patients (80%) relapsed, while 4 of 20 (20%) maintained normal platelet values after 4-12 months' follow up. Statistical analysis of the platelet count on day five of treatment enabled us to divide positive responders into three groups: good, intermediate, and poor. The possible mode of action and clinical application of high dose immunoglobulin are discussed. PMID:6685997

  18. Role of immunoglobulins in neonatal sepsis

    PubMed Central

    Capasso, L; Borrelli, AC; Cerullo, J; Pisanti, R; Figliuolo, C; Izzo, F; Paccone, M; Ferrara, T; Lama, S; Raimondi, F

    2015-01-01

    Neonates, especially VLBW, are at high risk for sepsis related morbidity and mortality for immaturity of their immune system and invasive NICU practices. The paucity of immunoglobulins in preterm neonates consequently to the immaturity of immune system contributes to their high risk for systemic infection. The use of intravenous IgM enriched immunoglobulins, with higher antimicrobial activity than standard IgG, has been demonstrated in a retrospective study to reduce short term mortality in VLBW infant with proven sepsis. Larger, randomized prospective trials given the enormous burden of morbidity and mortality imposed by neonatal sepsis should urgently be addressed not only to validate this results but also to tailor the optimal scheme of treatment. PMID:25674546

  19. Artificial Affinity Proteins as Ligands of Immunoglobulins

    PubMed Central

    Mouratou, Barbara; Béhar, Ghislaine; Pecorari, Frédéric

    2015-01-01

    A number of natural proteins are known to have affinity and specificity for immunoglobulins. Some of them are widely used as reagents for detection or capture applications, such as Protein G and Protein A. However, these natural proteins have a defined spectrum of recognition that may not fit specific needs. With the development of combinatorial protein engineering and selection techniques, it has become possible to design artificial affinity proteins with the desired properties. These proteins, termed alternative scaffold proteins, are most often chosen for their stability, ease of engineering and cost-efficient recombinant production in bacteria. In this review, we focus on alternative scaffold proteins for which immunoglobulin binders have been identified and characterized. PMID:25647098

  20. Autoreactivity of primary human immunoglobulins ancestral to hypermutated human antibodies that neutralize HCMV.

    PubMed

    McLean, Gary R; Cho, Chin-wen; Schrader, John W

    2006-05-01

    The human antibody response to the AD-2S1 epitope of glycoprotein B (gB) of human cytomegalovirus (HCMV) is dominated by a family of closely related somatically mutated antibodies. These antibodies neutralize viral infectivity and the genes encoding them are derived from two commonly used germ-line variable (V) region genes, IGHV3-30 and IGKV3-11. Recombination of these V genes with the appropriate junctional diversity generates genes that encode primary immunoglobulins that bind to AD-2S1. To further understand the initial primary immunoglobulin response to AD-2S1 we synthesized the germ-line-based ancestor of one such family of antibodies and showed that it bound gB at the AD-2S1 epitope. Here we show that the germ-line ancestor of a second family of antibodies likewise binds to gB. We further show that one of the ancestral primary immunoglobulins, but not the other, also recognized autoantigens. In contrast, the hypermutated derivatives did not demonstrate autoreactivity and minor structural changes in the primary immunoglobulin were sufficient to generate or abolish autoreactivity or to change specificity. Thus, our demonstration that the ancestor of a highly mutated, non-autoreactive antiviral IgG antibody binds nuclear and cell-surface autoantigens indicates for the first time that self-reactivity is not necessarily a barrier to development into a follicular B lymphocyte that undergoes antigen-initiated affinity maturation.

  1. [BIOLOGICAL AND IMMUNOCHEMICAL PROPERTIES OF POLYREACTIVE IMMUNOGLOBULINS].

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A previously unknown phenomenon of acquired polyreactivity for serum immunoglobulins, which were subjected either to solutions of KSCN (3.0-5.0 M), low/high pH (pH 2.2-3.0), or heating to 58-60 degrees C, was described by us in 1990 year. Much later, eleven years after that, similar data were published by others, which completely confirmed our results concerning the influence of either chaotropic ions or the drastic shift of pH on immunoglobulins polyreactive properties. Our further investigations of polyreactive serum immunoglobulins (PRIG) properties have shown that the mechanism of non-specific interaction between PRIG and antigens much differs from the mechanism of interaction between specific antibodies and corresponding antigens. Later we have shown that the increasing of PRIG reactivity could be induced in vivo, and PRIG are one of serum components for human or animal sera. Then, it could be suggested that PRIG can perform certain biological functions. Studying of PRIG's effect on the phagocytosis of microbes by peritoneal cells or the tumor growth have shown that PRIG can play a certain role in protecting the body from infections and probably can influence on the development of various pathological processes. Recently we have also found that PRIG IgG contents significantly increases in aged people. These data demonstrate that further investigations of PRIG's immunochemical properties and studying of their biological role in organism protection from various diseases is very intriguing and important.

  2. [BIOLOGICAL AND IMMUNOCHEMICAL PROPERTIES OF POLYREACTIVE IMMUNOGLOBULINS].

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A previously unknown phenomenon of acquired polyreactivity for serum immunoglobulins, which were subjected either to solutions of KSCN (3.0-5.0 M), low/high pH (pH 2.2-3.0), or heating to 58-60 degrees C, was described by us in 1990 year. Much later, eleven years after that, similar data were published by others, which completely confirmed our results concerning the influence of either chaotropic ions or the drastic shift of pH on immunoglobulins polyreactive properties. Our further investigations of polyreactive serum immunoglobulins (PRIG) properties have shown that the mechanism of non-specific interaction between PRIG and antigens much differs from the mechanism of interaction between specific antibodies and corresponding antigens. Later we have shown that the increasing of PRIG reactivity could be induced in vivo, and PRIG are one of serum components for human or animal sera. Then, it could be suggested that PRIG can perform certain biological functions. Studying of PRIG's effect on the phagocytosis of microbes by peritoneal cells or the tumor growth have shown that PRIG can play a certain role in protecting the body from infections and probably can influence on the development of various pathological processes. Recently we have also found that PRIG IgG contents significantly increases in aged people. These data demonstrate that further investigations of PRIG's immunochemical properties and studying of their biological role in organism protection from various diseases is very intriguing and important. PMID:26502695

  3. Interaction of immunoglobulin glycopeptides with concanavalin A.

    PubMed

    Kornfeld, R; Ferris, C

    1975-04-10

    A number of intact and partially degraded immunoglobulin glycopeptides have been tested for their ability to interact with concanavalin A. The degraded glycopeptides were prepared by using purified glycosidases to remove sugar residues from the nonreducing ends of the oligosaccharide chains of intact glycopeptides. A quantitative and sensitive assay was devised to measure the potency of the glycopeptides as haptene inhibitors of 125I-concanavalin A binding to guinea pig erythrocytes. The most potent haptene, derived from an immunoglobulin G glycopeptide, had a branched chain oligosaccharide with two GlcNAc (see article) Man (see article) nonreducing termini linked to a mannose residue in the core. The other very potent glycopeptide was an immunoglobulin E high mannose glycopeptide which contained 3 terminal alpha-mannose residues and 1 internal 2-O-mannose residue. Removal of terminal beta-N-acetylglucosamine residues or alpha-mannose residues reduced the activity of these and other glycopeptides as inhibitors of 125I-concanavalin A binding. It was concluded that the ability of these glycopeptides to interact with concanavalin A is dependent on their content of terminal beta-N-acetylglucosamine residues, terminal alpha-mannose residues, and also internal mannose residues substituted on the C-2 hydroxyl group, and that the saccharide combining site of concanavalin A must be able to bind several sugar residues.

  4. Tick-Borne Encephalitis Virus-Neutralizing Antibodies in Different Immunoglobulin Preparations

    PubMed Central

    Rabel, Philip O.; Planitzer, Christina B.; Farcet, Maria R.

    2012-01-01

    Patients with primary immunodeficiency (PIDs) depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG). Using the tick-borne encephalitis virus (TBEV), geographic variability in IVIG antibody content was shown. Care should therefore be exercised when treating PIDs in a given geography, as only locally sourced plasma contains the antibody specificities against the circulating pathogens in the given locality. PMID:22379062

  5. A new immunoglobulin variant: gamma3 heavy chain disease protein CHI.

    PubMed Central

    Frangione, B

    1976-01-01

    Protein CHI is a defective human gamma3 heavy chain immunoglobulin with a deletion encompassing a portion of the variable and constant regions. Joining of the two pieces takes place at the beginning of an extra fragment (Fh) in the constant region where repetitive sequences are found, apparently as the result of gene duplications and/or unequal crossover between gamma genes. It is postulated that a 45 nucleotide fragment is the repetitive unit coding for the extra fragment. PMID:818639

  6. Long-term immunoglobulin therapy for chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Rajabally, Yusuf A

    2015-05-01

    Immunoglobulins are an effective but expensive treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the goal is to improve function, use of functional scales to monitor therapy is not widespread. Limited recent evidence suggests that doses lower than those used traditionally may be as effective. There are no proven correlations of effective dose with weight, disease severity, or duration. The clinical course of CIDP is heterogeneous and includes monophasic forms and complete remissions. Careful monitoring of immunoglobulin use is necessary to avoid overtreatment. Definitive evidence for immunoglobulin superiority over steroids is lacking. Although latest trial evidence favors immunoglobulins over steroids, the latter may result in higher remission rates and longer remission periods. This article addresses the appropriateness of first-line, high-dose immunoglobulin treatment for CIDP and reviews important clinical questions regarding the need for long-term therapy protocols, adequate monitoring, treatment withdrawal, and consideration of corticosteroids as an alternative to immunoglobulin therapy.

  7. Characterization of the immunoglobulin A protease of Ureaplasma urealyticum.

    PubMed Central

    Spooner, R K; Russell, W C; Thirkell, D

    1992-01-01

    Ureaplasma urealyticum strains of all serotypes express a specific human immunoglobulin A1 protease that cleaves immunoglobulin A1 to produce intact Fab and Fc fragments. The use of a variety of inhibitors suggests that the enzyme is a serine protease. N-terminal sequencing of the Fc digestion product showed that the enzyme cleaves between the proline and threonine residues 235 and 236 in the hinge region of the heavy chain of immunoglobulin A1. Images PMID:1587621

  8. Scope of action of the immunoglobulin mutator system.

    PubMed

    Wabl, M R; Jäck, H M; von Borstel, R C; Steinberg, C M

    1989-01-01

    The authors have developed a method to measure the rate of spontaneous mutations taking place in IgH, the gene encoding the immunoglobulin heavy chain. When an amber chain-termination codon mutates to a sense codon, translation of the polypeptide chain will be completed, and mutant cells producing the heavy chain can be detected with a fluorescent labelled antibody. The protocol used is the compartmentalization test which minimizes any effect of selection. In subclones of the pre-B lymphocyte line 18-81, the spontaneous mutation rate in the part of IgH encoding the variable region is somewhat greater than 10(-5) mutations per base pair per generation. This supports the hypothesis that hypermutation is not dependent on cell stimulation by an antigen. In a hybrid between a cell of this line and a myeloma (which represents the terminal stage of the B-cell lineage), the mutation rate was too low to be determined by this test, less than 10(-9). When the same loss to gain procedure system was used with an opal chain-terminating codon in the part of IgH encoding the constant region (C mu), a high rate of reversion by deletion was found. Long (more than one exon) and short (less than one exon) deletions occurred at rates of 1.7 x 10(-5) and 1.4 x 10(-7) per generation, respectively. It is thought that the high rate of deletion is not related to somatic hypermutation but rather to DNA rearrangement during the heavy-chain class switch, which is occurring in these pre-B cell lines. The point mutation rate was too low to be detected above the background of deletion mutants, less than 5 x 10(-8). The immunoglobulin mutator system works weakly, if at all, on two other, nonimmunoglobulin, genes tested: B2m (beta 2 microglobulin) and the gene for ouabain resistance. PMID:2512197

  9. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

    Giers, Günther; Wenzel, Folker; Stockschläder, Markus; Riethmacher, Regina; Lorenz, Horst; Tutschek, Boris

    2010-01-01

    Background Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and Methods We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. Results There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×109/L and 130×109/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. Conclusions In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions. PMID:20534698

  10. Hydrometer test for estimation of immunoglobulin concentration in bovine colostrum.

    PubMed

    Fleenor, W A; Stott, G H

    1980-06-01

    A practical field method for measuring immunoglobulin concentration in bovine colostrum has been developed from the linear relationship between colostral specific gravity and immunoglobulin concentration. Fourteen colostrums were collected within 24 h postpartum from nursed and unnursed cows and were assayed for specific gravity and major colostral constituents. Additionally, 15 colostrums were collected immediately postpartum prior to suckling and assayed for specific gravity and immunoglobulin concentration. Regression analysis provided an equation to estimate colostral immunoglobulin concentration from the specific gravity of fresh whole colostrum. From this, a colostrometer was developed for practical field use.

  11. Secondary hypogammaglobulinemia in Waldmann's disease treated with subcutaneous immunoglobulins.

    PubMed

    Patuzzo, G; Tinazzi, E; Micheletti, M; Puccetti, A; Lunardi, C

    2016-03-01

    Primary intestinal lymphangiectasia (PIL) is rare disorder characterized by congenital malformation or obstruction of intestinal lymphatic drainage; it is responsible for protein losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL management. The administration of intravenous immunoglobulins does not always lead to satisfactory plasma levels and therefore the replacement therapy with immunoglobulins is controversial. We describe here the case of a patient with PIL and severe hypogammaglobulinemia treated with immunoglobulins. The striking aspect of this case is the clinical and serological benefit obtained with the subcutaneous compared to the intravenous immunoglobulins administration. PMID:26934740

  12. Hydrometer test for estimation of immunoglobulin concentration in bovine colostrum.

    PubMed

    Fleenor, W A; Stott, G H

    1980-06-01

    A practical field method for measuring immunoglobulin concentration in bovine colostrum has been developed from the linear relationship between colostral specific gravity and immunoglobulin concentration. Fourteen colostrums were collected within 24 h postpartum from nursed and unnursed cows and were assayed for specific gravity and major colostral constituents. Additionally, 15 colostrums were collected immediately postpartum prior to suckling and assayed for specific gravity and immunoglobulin concentration. Regression analysis provided an equation to estimate colostral immunoglobulin concentration from the specific gravity of fresh whole colostrum. From this, a colostrometer was developed for practical field use. PMID:7400425

  13. Immunoglobulin Fc gamma receptor promotes immunoglobulin uptake, immunoglobulin-mediated calcium increase, and neurotransmitter release in motor neurons

    NASA Technical Reports Server (NTRS)

    Mohamed, Habib A.; Mosier, Dennis R.; Zou, Ling L.; Siklos, Laszlo; Alexianu, Maria E.; Engelhardt, Jozsef I.; Beers, David R.; Le, Wei-dong; Appel, Stanley H.

    2002-01-01

    Receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) facilitate IgG uptake by effector cells as well as cellular responses initiated by IgG binding. In earlier studies, we demonstrated that amyotrophic lateral sclerosis (ALS) patient IgG can be taken up by motor neuron terminals and transported retrogradely to the cell body and can alter the function of neuromuscular synapses, such as increasing intracellular calcium and spontaneous transmitter release from motor axon terminals after passive transfer. In the present study, we examined whether FcgammaR-mediated processes can contribute to these effects of ALS patient immunoglobulins. F(ab')(2) fragments (which lack the Fc portion) of ALS patient IgG were not taken up by motor axon terminals and were not retrogradely transported. Furthermore, in a genetically modified mouse lacking the gamma subunit of the FcR, the uptake of whole ALS IgG and its ability to enhance intracellular calcium and acetylcholine release were markedly attenuated. These data suggest that FcgammaRs appear to participate in IgG uptake into motor neurons as well as IgG-mediated increases in intracellular calcium and acetylcholine release from motor axon terminals. Copyright 2002 Wiley-Liss, Inc.

  14. [Dermatomyositis and Panniculitis: the function of immunoglobulins].

    PubMed

    Abdelhafidh, Nadia Ben; Toujeni, Sana; Kefi, Asma; Bousetta, Najeh; Sayhi, Sameh; Gharsallah, Imen; Othmani, Salah

    2016-01-01

    Panniculitis is an inflammatory disease of subcutaneous adipose tissue which is rarely associated with dermatomyositis. It can occur before, after or simultaneously with muscle damage. In most cases, the evolution of panniculitis and of other dermatomyositis affections is favorable with corticosteroids and/or immunosuppressants. We report the case of a 48 year-old patient who developed panniculitis lesions 2 months before having muscular signs. Skin involvement was resistant to corticosteroid treatment associated with immunosuppressants drugs. This led to the use of polyvalent immunoglobulin treatment improving both skin and muscle damage. PMID:27516827

  15. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids. Measurement of immunoglobulin G Fc fragments aids in the diagnosis of plasma cell...

  16. The immunoglobulins of cold-blooded vertebrates.

    PubMed

    Pettinello, Rita; Dooley, Helen

    2014-11-24

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species.

  17. Autoantibodies and immunoglobulins among atomic bomb survivors

    SciTech Connect

    Fujiwara, Saeko; Akahoshi, Masazumi; Kodama, Kazunori; Shimaoka, Katsutaro; Akiyama, Mitoshi; Carter, R.L.; Yamakido, Michio

    1994-01-01

    The purpose of this study was to determine if exposure to atomic bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from 0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be increased in the individuals exposed to higher radiation doses. The IgA level in females and the IgM level in both sexes increased as radiation dose increased, although the effects of radiation exposure were not large. No effect of radiation was found on the prevalence of antinuclear antibody, antithyroglobulin antibody and anti-thyroid-microsomal antibody or on the levels of IgG and IgE. 32 refs., 2 figs., 3 tabs.

  18. The immunoglobulins of cold-blooded vertebrates.

    PubMed

    Pettinello, Rita; Dooley, Helen

    2014-01-01

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more "conventional" mammalian species. PMID:25427250

  19. Immunoglobulin synthesis in primary and myeloma amyloidosis.

    PubMed Central

    Preud'homme, J L; Ganeval, D; Grünfeld, J P; Striker, L; Brouet, J C

    1988-01-01

    Bone marrow cells from 14 patients with primary amyloidosis and two patients with myeloma amyloidosis were studied by immunofluorescence and biosynthesis experiments after incorporation of radioactive amino acids. Cells from four patients affected with non-myeloma secondary amyloidosis were also studied as controls. In primary amyloidosis, monoclonal plasma cell populations were demonstrated by immunofluorescence in virtually every case, even in patients without serum and urine monoclonal immunoglobulin and with a normal percentage of bone marrow plasma cells. Biosynthesis experiments showed the secretion of large amounts of free light chains, most often of the lambda type, in every primary or myeloma amyloidosis case and the presence of light chain fragments in almost all cases. Special features in certain patients were the synthesis of short gamma chains (two cases), assembly block at the HL half molecule level of a monoclonal IgA (one case) and secretion of decameric abnormally large kappa chains (one case). This is in contrast with non-myelomatous secondary amyloidosis where the distribution of bone marrow plasma cells was normal by immunofluorescence and where normal sized immunoglobulins were synthesized, without free light chain secretion and fragments. These data confirm that primary amyloidosis belongs to plasma cell dyscrasias and emphasize the role of free light chains and light chain fragments in the pathogenesis of amyloid deposition. PMID:3145161

  20. The Immunoglobulins of Cold-Blooded Vertebrates

    PubMed Central

    Pettinello, Rita; Dooley, Helen

    2014-01-01

    Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species. PMID:25427250

  1. [Carbohydrate component of immunoglobulin G in cattle suffering from leukosis].

    PubMed

    Meged', E F; Korotkoruchko, V P; Radionov, N T

    1982-01-01

    No essential differences are found in the composition and total amount of carbohydrates in the studied preparations of the immunoglobulin G subfraction in cattle suffering from leucosis and of the immunoglobulin G subfraction, identical in evolution, in healthy animals. It is shown that the main mass of carbohydrates is connected with Fc-fragment and heavy chains of the protein under study. PMID:7135515

  2. Helicobacter pylori infection in patients with selective immunoglobulin E deficiency

    PubMed Central

    Magen, Eli; Schlesinger, Menachem; Ben-Zion, Itzhak; Vardy, Daniel

    2015-01-01

    AIM: To investigate the prevalence and clinical characteristics of Helicobacter pylori (H. pylori)-infected dyspeptic patients with selective immunoglobulin E deficiency (IgEd). METHODS: All individuals who underwent serum total immunoglobulin E (IgE) measurement at the Leumit Healthcare Services (Israel) in 2012 were identified in an electronic database search (n = 18487). From these, selected case group subjects were ≥ 12 years of age and had serum total IgE < 2 kIU/L (n = 158). The control group was selected from a random sampling of the remaining subjects ≥ 12 years of age to obtain a case-control ratio of 1:20 (n = 3160). Dyspeptic diseases, diagnosed no more than 5 years before serum total IgE testing, were identified and retrieved from the electronic database using specific International Classification of Diseases diagnostic codes. Results of C13-urea breath tests were used to identify subjects infected with H. pylori. Categorical variables between case and control subjects were analyzed using Fisher’s exact tests, whereas continuous variables were analyzed using χ2 tests. RESULTS: Dyspepsia was present in 27.2% (43/158) of case subjects and 22.7% (718/3160) of controls. Of these, significantly more case subjects (32/43, 74.4%) than controls (223/718, 31.1%) were positive for H. pylori (P < 0.01). Esophagogastroduodenoscopy was performed in 19 case and 94 control subjects, revealing that gastritis was more prevalent in IgEd case subjects than in controls (57.9% vs 29.8%, P < 0.05). Furthermore, a significantly greater proportion of case subjects presented with peptic duodenal ulcers (63.2% vs 15.9%, P < 0.01). Histopathologic examination showed marked chronic inflammation, lymphoid follicle formation and prominent germinal centers, with polymorphonuclear cell infiltration of gastric glands, that was similar in case and control biopsy tissues. Finally, IgEd case subjects that underwent esophagogastroduodenoscopy were more likely to exhibit treatment

  3. The Biology of Intestinal Immunoglobulin A Responses

    PubMed Central

    Cerutti, Andrea; Rescigno, Maria

    2011-01-01

    The gut mucosa is exposed to a large community of commensal bacteria that are required for the processing of nutrients and the education of the local immune system. Conversely, the gut immune system generates innate and adaptive responses that shape the composition of the local microbiota. One striking feature of intestinal adaptive immunity is its ability to generate massive amounts of noninflammatory immunoglobulin A (IgA) antibodies through multiple follicular and extrafollicular pathways that operate in the presence or absence of cognate T-B cell interactions. Here we discuss the role of intestinal IgA in host-commensal mutualism, immune protection, and tolerance and summarize recent advances on the role of innate immune cells in intestinal IgA production. PMID:18549797

  4. Immunoglobulin Responses at the Mucosal Interface

    PubMed Central

    Chen, Kang; Chorny, Alejo

    2011-01-01

    Mucosal surfaces are colonized by large communities of commensal bacteria and represent the primary site of entry for pathogenic agents. To prevent microbial intrusion, mucosal B cells release large amounts of immunoglobulin (Ig) molecules through multiple follicular and extrafollicular pathways. IgA is the most abundant antibody isotype in mucosal secretions and owes its success in frontline immunity to its ability to undergo transcytosis across epithelial cells. In addition to translocating IgA onto the mucosal surface, epithelial cells educate the mucosal immune system as to the composition of the local microbiota and instruct B cells to initiate IgA responses that generate immune protection while preserving immune homeostasis. Here we review recent advances in our understanding of the cellular interactions and signaling pathways governing IgA production at mucosal surfaces and discuss new findings on the regulation and function of mucosal IgD, the most enigmatic isotype of our mucosal antibody repertoire. PMID:21219173

  5. Rheumatoid factors, B cells and immunoglobulin genes.

    PubMed

    Jefferis, R

    1995-04-01

    The paradigm of self, non-self discrimination in the immune system is under review as autoreactive B or T cells are increasingly delineated within normal individuals. The products of autoreactive B cells are, mostly, polyspecific IgM antibodies of low affinity. These 'natural' antibodies include rheumatoid factors (RF) encoded by unmutated germline immunoglobulin genes. In rheumatoid arthritis (RA) the RF may be of the IgM, IgG or IgA isotype, show evidence of somatic mutation and have increased affinity; consistent with maturation of an antigen driven immune response. This response could be initiated or driven by an auto-immunogenic form of IgG or an exogenous cross-reactive antigen. Changes in galactosylation of IgG have been reported to be a valuable diagnostic and prognostic indicator in RA. Speculation that these changes may precipitate some of the disease processes is critically reviewed.

  6. Immunoglobulin allotypes in Ecuadorian Cayapa Indians.

    PubMed

    Kron, M A; Gately, L; Pandey, J P; Jurado, M H; Rumbea Guzman, J

    1994-05-01

    Indigenous Indian groups comprise approximately 20% of Ecuador's population, the third largest percentage in all of Central or South America, yet immunogenetic data on these groups are lacking in the literature. In the course of population migration studies, sera collected from 65 Ecuadorians living in the northern province of Esmeraldas were typed for six GM and two KM markers. The study population consisted of 47 Cayapa Indians and 18 blacks of African origin, descendants of slaves imported into the area during the seventeenth century. The Cayapa demonstrated three GM phenotypes, two of which are common to other South American Indian tribes. The frequency of KM1 positive Cayapa Indians (63%) is similar to other South American Indian tribes, but is significantly greater than the Huaorani of eastern Ecuador (2%), the only other Ecuadorian Indian group for whom limited immunoglobulin allotype data are available (chi 2 = 35.8, P < 0.0001). PMID:8168827

  7. Gene conversion in human rearranged immunoglobulin genes.

    PubMed

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  8. T Cell Immunoglobulin Mucin-3 Crystal Structure Reveals a Galectin-9-Independent Ligand-Binding Surface

    SciTech Connect

    Cao,E.; Zang, X.; Ramagopal, U.; Mukhopadhaya, A.; Fedorov, A.; Fedorov, E.; Zencheck, W.; Lary, J.; Cole, J.; et al.

    2007-01-01

    The T cell immunoglobulin mucin (Tim) family of receptors regulates effector CD4+ T cell functions and is implicated in autoimmune and allergic diseases. Tim-3 induces immunological tolerance, and engagement of the Tim-3 immunoglobulin variable (IgV) domain by galectin-9 is important for appropriate termination of T helper 1-immune responses. The 2 {angstrom} crystal structure of the Tim-3 IgV domain demonstrated that four cysteines, which are invariant within the Tim family, form two noncanonical disulfide bonds, resulting in a surface not present in other immunoglobulin superfamily members. Biochemical and biophysical studies demonstrated that this unique structural feature mediates a previously unidentified galectin-9-independent binding process and suggested that this structural feature is conserved within the entire Tim family. The current work provided a graphic example of the relationship between sequence, structure, and function and suggested that the interplay between multiple Tim-3-binding activities contributes to the regulated assembly of signaling complexes required for effective Th1-mediated immunity.

  9. Immunoglobulin genes and antibody responses in the spotted wolffish (Anarhichas minor Olafsen).

    PubMed

    Espelid, S; Halse, M; Solem, S T; Jørgensen, T O

    2001-07-01

    The spotted wolffish Anarhichas minor Olafsen is a promising new species in aquaculture in the cold waters of northern Norway. In this paper, some basic immunological studies of this marine species are reported. Of comparative interest are the cDNA sequences of the immunoglobulin transcript and the antibody responses to model antigens. Of more practical importance are the humoral immune responses and antibody specificities to potentially pathogenic bacteria. Full length cDNA clones encoding the immunoglobulin heavy and light chains in the spotted wolffish were sequenced demonstrating variable degrees of similarity to other teleost fish species. Also in the spotted wolffish the CH4 domain was deleted in the transmembrane form of the immunoglobulin heavy chain (IgH) as a receptor on B cells, with the transmembrane exon spliced directly to the CH3 domain. The antibody responses to various antigens like hapten-carrier molecules, protein antigens and bacterial pathogens were relatively high, but with some interesting exceptions. Anti-hapten responses to NIP and FITC were high while anti-DNS responses were low, but more surprisingly, there was hardly any B-cell response to the carrier molecule LPH. On the other hand, protein antigens like CGG and BSA were highly immunogenic in the spotted wolffish as were the bacterial antigens Vibrio anguillarum, V. salmonicida and Aeromonas salmonicida.

  10. Clonal deletion of specific thymocytes by an immunoglobulin idiotype.

    PubMed Central

    Bogen, B; Dembic, Z; Weiss, S

    1993-01-01

    We have investigated whether immunoglobulin can induce clonal deletion of thymocytes by employing two strains of transgenic mice. One strain is transgenic for an alpha/beta T cell receptor (TCR) which recognizes a processed idiotypic peptide of the lambda 2(315) light chain variable region, bound to the I-Ed class II major histocompatibility complex molecule. The other mouse strain is transgenic for the lambda 2(315) gene. Double transgenic offspring from a TCR-transgenic female mated with a lambda 2(315) transgenic male exhibit a pronounced clonal deletion of CD4+CD8+ thymocytes. Analysis of neonates from the reciprocal (lambda 2(315)-transgenic female x TCR-transgenic male) cross suggests that the deletion in double transgenic offspring most likely is caused by lambda 2(315) produced within the thymus rather than by maternally derived IgG, lambda 2(315). Nevertheless, IgG, lambda 2(315) can cause deletion of CD4+CD8+ thymocytes when injected in large amounts intraperitoneally into either adult or neonatal TCR-transgenic mice. Deletion is evident 48 and 72 h after injection, but by day 7 the thymus has already regained its normal appearance. A serum concentration of several hundred microgram/ml is required for deletion to be observed. Therefore, the heterogeneous idiotypes of serum Ig are probably each of too low concentration to cause thymocyte deletion in normal animals. Images PMID:8428591

  11. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

    PubMed

    Yu, Guo-Yun; Mate, Suzanne; Garcia, Karla; Ward, Michael D; Brueggemann, Ernst; Hall, Matthew; Kenny, Tara; Sanchez-Lockhart, Mariano; Lefranc, Marie-Paule; Palacios, Gustavo

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

  12. Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals

    PubMed Central

    Hoehn, Kenneth B.; Gall, Astrid; Bashford-Rogers, Rachael; Fidler, S. J.; Kaye, S.; Weber, J. N.; McClure, M. O.; Kellam, Paul; Pybus, Oliver G.

    2015-01-01

    Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to anti-retroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received anti-retroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIV-infected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this, we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly, we find a significant association between observed Gini indices and sequencing read depth, and we conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection. PMID:26194755

  13. Esophageal Involvement of Immunoglobulin G4-Related Disease

    PubMed Central

    Oh, Ji Hyun; Lee, Tae Hee; Kim, Hyo Shik; Jung, Chan Sung; Lee, Joon Seong; Hong, Su Jin; Jin, So-Young

    2015-01-01

    Abstarct Immunoglobulin G4 (IgG4)-related disease is characterized by the typical histopathological features of a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, a high ratio of IgG4- to IgG-positive cells, storiform fibrosis (cellular fibrosis organized in an irregular whorled pattern), obliterative phlebitis, and variable presence of eosinophils. The disease exhibits systemic involvement but very rarely involves the esophagus. A 33-year-old man was admitted to our hospital for evaluation of a 1-year history of progressive dysphagia. Neck imaging revealed a 3.9-cm mass in the cervical esophagus and multifocal calcified lymph nodes in the lower neck and mediastinum. Two previous tertiary hospitals failed to diagnose the patient's condition despite the use of ultrasound-guided needle biopsy of the neck tumor. We performed neck imaging studies, a flexible endoscopic swallowing study, high-resolution manometry, upper endoscopy, and a review of the previous pathologic slides. The patient was finally diagnosed with IgG4-related esophagitis and showed a good response to corticosteroid therapy. We herein report a rare case of dysphagia associated with IgG4-related disease and present a review of the literature. PMID:26683918

  14. Immunoglobulin genes and their transcriptional control in teleosts.

    PubMed

    Hikima, Jun-ichi; Jung, Tae-Sung; Aoki, Takashi

    2011-09-01

    Immunoglobulin (Ig), which exists only in jawed vertebrates, is one of the most important molecules in adaptive immunity. In the last two decades, many teleost Ig genes have been identified by in silico data mining from the enormous gene and EST databases of many fish species. In this review, the organization of Ig gene segments, the expressed Ig isotypes and their transcriptional controls are discussed. The Ig heavy chain (IgH) locus in teleosts encodes the variable (V), the diversity (D), the joining (J) segments and three different isotypic constant (C) regions including Cμ, Cδ, and Cζ/τ genes, and is organized as a "translocon" type like the IgH loci of higher vertebrates. In contrast, the Ig light (L) chain locus is arranged in a "multicluster" or repeating set of VL, JL, and CL segments. The IgL chains have four isotypes; two κ L1/G and L3/F), σ (L2) and λ. The transcription of IgH genes in teleosts is regulated by a VH promoter and the Eμ3' enhancer, which both function in a B cell-specific manner. The location of the IgH locus, structure and transcriptional function of the Eμ3' enhancer are important to our understanding of the evolutional changes that have occurred in the IgH gene locus.

  15. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

    PubMed Central

    Giorgio, Floriana; Principi, Mariabeatrice; Losurdo, Giuseppe; Piscitelli, Domenico; Iannone, Andrea; Barone, Michele; Amoruso, Annacinzia; Ierardi, Enzo; Di Leo, Alfredo

    2015-01-01

    In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten “challenge” are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs’ range of 15–25/100 enterocytes, suggesting that there may be a “grey zone” of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association. PMID:26371035

  16. Seronegative Celiac Disease and Immunoglobulin Deficiency: Where to Look in the Submerged Iceberg?

    PubMed

    Giorgio, Floriana; Principi, Mariabeatrice; Losurdo, Giuseppe; Piscitelli, Domenico; Iannone, Andrea; Barone, Michele; Amoruso, Annacinzia; Ierardi, Enzo; Di Leo, Alfredo

    2015-09-08

    In the present narrative review, we analyzed the relationship between seronegative celiac disease (SNCD) and immunoglobulin deficiencies. For this purpose, we conducted a literature search on the main medical databases. SNCD poses a diagnostic dilemma. Villous blunting, intraepithelial lymphocytes (IELs) count and gluten "challenge" are the most reliable markers. Immunohistochemistry/immunofluorescence tissue transglutaminase (tTG)-targeted mucosal immunoglobulin A (IgA) immune complexes in the intestinal mucosa of SNCD patients may be useful. In our experience, tTG-mRNA was similarly increased in seropositive celiac disease (CD) and suspected SNCD, and strongly correlated with the IELs count. This increase is found even in the IELs' range of 15-25/100 enterocytes, suggesting that there may be a "grey zone" of gluten-related disorders. An immune deregulation (severely lacking B-cell differentiation) underlies the association of SNCD with immunoglobulin deficiencies. Therefore, CD may be linked to autoimmune disorders and immune deficits (common variable immunodeficiency (CVID)/IgA selective deficiency). CVID is a heterogeneous group of antibodies dysfunction, whose association with CD is demonstrated only by the response to a gluten-free diet (GFD). We hypothesized a familial inheritance between CD and CVID. Selective IgA deficiency, commonly associated with CD, accounts for IgA-tTG seronegativity. Selective IgM deficiency (sIgMD) is rare (<300 cases) and associated to CD in 5% of cases. We diagnosed SNCD in a patient affected by sIgMD using the tTG-mRNA assay. One-year GFD induced IgM restoration. This evidence, supporting a link between SNCD and immunoglobulin deficiencies, suggests that we should take a closer look at this association.

  17. Effect of zinc supplementation on mycospecific immunoglobulins in tuberculosis patients.

    PubMed

    Chattopadhyay, Dipak Kumar; Maity, Chitta Ranjan; Nag, Debabrata

    2010-02-01

    The effect of zinc supplementation on the serum level of IgA, IgG, IgM mycospecific immunoglobulins in tuberculosis patients alongwith normal control and disease control subjects were studied. It was observed that with antituberculous drugs for one month (without zinc supplementation), the serum level of immunoglobulins in tuberculosis subjects although decreased significantly, but with zinc supplementation along with antituberculous drugs for one month the decrease in the level of immunoglobulins in serum was more significant. This may be attributed to the effect of zinc supplementation favouring the normal compartmentalisation state of iron and also to the immunomodulatory effect of zinc.

  18. Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

    PubMed

    Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

    2009-11-01

    Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001), and healthy brothers and sisters from the fathers and mothers (p < 0,001). Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

  19. Variability for Categorical Variables

    ERIC Educational Resources Information Center

    Kader, Gary D.; Perry, Mike

    2007-01-01

    Introductory statistics textbooks rarely discuss the concept of variability for a categorical variable and thus, in this case, do not provide a measure of variability. The impression is thus given that there is no measurement of variability for a categorical variable. A measure of variability depends on the concept of variability. Research has…

  20. Rabbit anti-rabies immunoglobulins production and evaluation.

    PubMed

    Liu, Xinjian; Liu, Qiongqiong; Feng, Xiaomin; Tang, Qi; Wang, Zhongcan; Li, Suqing; Feng, Zhenqing; Zhu, Jin; Guan, Xiaohong

    2011-04-01

    Due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for HRIG and ERIG, especially for those people living in the developing countries. Because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by ELISA, affinity assay, immunofluorescence assay (IFA), immunocytochemistry, rapid fluorescent focus inhibition test (RFFIT). ELISA, affinity assay and IFA showed that rabbit RIG (RRIG) bound specifically to rabies virions. RFFIT result showed that RRIG has neutralization activity. This result was confirmed in vivo in a Kunming mouse challenge model and the protection rate of the treatment with RRIG was higher (25%) than that offered by HRIG when mice were challenged with a lethal RV dose. Our results demonstrate that RRIG is safe and efficacious as a candidate drug to replace rabies immunoglobulin in post-exposure prophylaxis.

  1. Recombinant Immunoglobulin A Specific for Influenza A Virus Hemagglutinin: Production, Functional Analysis, and Formation of Secretory Immunoglobulin A

    PubMed Central

    Shoji, Kentaro; Takahashi, Tadanobu; Kurohane, Kohta; Iwata, Koki; Matsuoka, Takeshi; Tsuruta, Shogo; Sugino, Takatomo; Miyake, Masaki; Suzuki, Takashi

    2015-01-01

    Abstract Secretory immunoglobulin (Ig) A (SIgA), comprised of dimeric IgA and secretory component (SC), is believed to provide a defense mechanism on the mucosal surface. Influenza A virus (IAV) hemagglutinin (HA)-specific SIgA is thought to play an important role in the prevention of IAV infection. However, the topical application of preformed IAV-specific SIgA has not been shown to prevent IAV infection. This is due to the difficulty in the production of antigen-specific IgA monoclonal antibodies (mAbs) and monoclonal SIgA. Here, a recombinant hybrid IgA (HIgA) was established that utilizes variable regions of an HA-specific mouse IgG mAb and the heavy chain constant region of a mouse IgA mAb. We expressed the dimeric HIgA in Chinese hamster ovary-K1 (CHO-K1) cells. When in vitro IAV infection of Madin–Darby canine kidney (MDCK) cells was tested, 10 times lower concentrations of HIgA were able to inhibit it as compared with an HA-specific IgG with the same variable regions. A functional hybrid secretory IgA (HSIgA) was also produced through incubation of the dimeric HIgA with recombinant mouse SC in vitro. It was demonstrated that HSIgA could be separated from the dimeric HIgA on size exclusion chromatography. This study provides a basic strategy for investigating the role of SIgA upon IAV infection on the mucosal surface. PMID:25658886

  2. Immunoglobulin light chains, glycosaminoglycans and amyloid.

    SciTech Connect

    Stevens, F. J.; Kisilevsky, R.; Biosciences Division; Queen's Univ.

    2000-03-01

    Immunoglobulin light chains are the precursor proteins for fibrils that are formed during primary amyloidosis and in amyloidosis associated with multiple myeloma. As found for the approximately 20 currently described forms of focal, localized, or systemic amyloidoses, light chain-related fibrils extracted from physiological deposits are invariably associated with glycosaminoglycans, predominantly heparan sulfate. Other amyloid-related proteins are either structurally normal, such as g2-microglobulin and islet amyloid polypeptide, fragments of normal proteins such as serum amyloid A protein or the precursor protein of the g peptide involved in Alzheimer's disease, or are inherited forms of single amino acid variants of a normal protein such as found in the familial forms of amyloid associated with transthyretin. In contrast, the primary structures of light chains involved in fibril formation exhibit extensive mutational diversity rendering some proteins highly amyloidogenic and others non-pathological. The interactions between light chains and glycosaminoglycans are also affected by amino acid variation and may influence the clinical course of disease by enhancing fibril stability and contributing to resistance to protease degradation. Relatively little is currently known about the mechanisms by which glycosaminoglycans interact with light chains and light-chain fibrils. It is probable that future studies of this uniquely diverse family of proteins will continue o shed light on the processes of amyloidosis, and contribute as well to a greater understanding of the normal physiological roles of glycosaminoglycans.

  3. Ulcerative Colitis and Immunoglobulin G4

    PubMed Central

    Kuwata, Go; Koizumi, Koichi; Tabata, Taku; Hara, Seiichi; Kuruma, Sawako; Fujiwara, Takashi; Chiba, Kazuro; Egashira, Hideto; Fujiwara, Junko; Arakawa, Takeo; Momma, Kumiko; Horiguchi, Shinichiro

    2014-01-01

    Background/Aims Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Methods Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. Results UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p<0.05). Conclusions UC is sometimes associated with AIP, but it seems that UC is not a manifestation of IgG4-related disease. Infiltration of IgG4-positive plasma cells is sometimes detectable in the colonic mucosa of UC patients and is associated with disease activity. PMID:24516698

  4. Dermatomyosite et panniculite: place des immunoglobulines

    PubMed Central

    Abdelhafidh, Nadia Ben; Toujeni, Sana; Kefi, Asma; Bousetta, Najeh; Sayhi, Sameh; Gharsallah, Imen; Othmani, Salah

    2016-01-01

    La panniculite est une maladie inflammatoire du tissu adipeux sous-cutané rarement associée à la dermatomyosite. Elle peut survenir avant, après ou en même temps que l'atteinte musculaire. Dans la plupart des cas, l’évolution de la panniculite et des autres atteintes de la dermatomyosite est favorable sous traitement corticoïde et/ou immunosuppresseur. Nous rapportons le cas d'une patiente âgée de 48 ans ayant présenté des lésions de panniculite précédant de 2 mois les signes musculaires. L'atteinte cutanée était résistante au traitement corticoïde associés aux immunosuppresseurs ce qui a nécessité le recours au traitement par Immunoglobulines polyvalentes permettant ainsi une amélioration à la fois de l'atteinte cutanée et musculaire. PMID:27516827

  5. Immunoglobulin class-switch recombination deficiencies.

    PubMed

    Durandy, Anne; Kracker, Sven

    2012-01-01

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches. PMID:22894609

  6. Immunoglobulin: production, mechanisms of action and formulations

    PubMed Central

    Novaretti, Marcia Cristina Zago; Dinardo, Carla Luana

    2011-01-01

    Human immunoglobulin (Ig) began to be applied in the clinical practice with the treatment of primary immunodeficiencies. Quickly, applications of Ig increased, as its anti-inflammatory and immunomodulatory functions were elucidated. Currently, Ig is the most commonly used blood product. Ig is obtained by processing plasma; methods, in particular, techniques to reduce plasma viral loads have been evolving over the years and include: pasteurization, solvent/ detergent treatment, caprylic acid treatment and nanofiltration. These methods contribute to increased safety and quality of blood products. The mechanisms of action of Ig not only involve the blockade of Fc receptors of phagocytes, but also control complement pathways, idiotype-anti-idiotype dimer formation, blockage of superantigen binding to T cells, inhibition of dendritic cells and stimulation of regulatory T cells (Tregs). There are several formulations of Ig available, each one with its own peculiar characteristics. In Brazil, there is stringent legislation regulating the quality of Ig. Only Ig products that completely fulfill the quality control criteria are released for use. These standards involve different tests from visual inspection to determination of anti-complementary activity. This paper will further review the history and current status of Ig, including its production and mechanisms of action. The formulations available in Brazil and also the criteria of quality control currently applied will be presented. PMID:23049343

  7. Immunoglobulin isotypes in Atlantic salmon, Salmo salar.

    PubMed

    Hordvik, Ivar

    2015-02-27

    There are three major immunoglobulin (Ig) isotypes in salmonid fish: IgM, IgD and IgT, defined by the heavy chains μ, δ and τ, respectively. As a result of whole genome duplication in the ancestor of the salmonid fish family, Atlantic salmon (Salmo salar) possess two highly similar Ig heavy chain gene complexes (A and B), comprising two μ genes, two δ genes, three intact τ genes and five τ pseudogenes. The μA and μB genes correspond to two distinct sub-populations of serum IgM. The IgM-B sub-variant has a characteristic extra cysteine near the C-terminal part of the heavy chain and exhibits a higher degree of polymer disulfide cross-linking compared to IgM-A. The IgM-B:IgM-A ratio in serum is typically 60:40, but skewed ratios are also observed. The IgT isotype appears to be specialized to mucosal immune responses in salmonid fish. The concentration of IgT in serum is 100 to 1000 times lower than IgM. Secreted forms of IgD have been detected in rainbow trout, but not yet in Atlantic salmon.

  8. Cytomegalovirus Immunoglobulin After Thoracic Transplantation: An Overview.

    PubMed

    Grossi, Paolo; Mohacsi, Paul; Szabolcs, Zoltán; Potena, Luciano

    2016-03-01

    Cytomegalovirus (CMV) is a highly complex pathogen which, despite modern prophylactic regimens, continues to affect a high proportion of thoracic organ transplant recipients. The symptomatic manifestations of CMV infection are compounded by adverse indirect effects induced by the multiple immunomodulatory actions of CMV. These include a higher risk of acute rejection, cardiac allograft vasculopathy after heart transplantation, and potentially bronchiolitis obliterans syndrome in lung transplant recipients, with a greater propensity for opportunistic secondary infections. Prophylaxis for CMV using antiviral agents (typically oral valganciclovir or intravenous ganciclovir) is now almost universal, at least in high-risk transplants (D+/R-). Even with extended prophylactic regimens, however, challenges remain. The CMV events can still occur despite antiviral prophylaxis, including late-onset infection or recurrent disease, and patients with ganciclovir-resistant CMV infection or who are intolerant to antiviral therapy require alternative strategies. The CMV immunoglobulin (CMVIG) and antiviral agents have complementary modes of action. High-titer CMVIG preparations provide passive CMV-specific immunity but also exert complex immunomodulatory properties which augment the antiviral effect of antiviral agents and offer the potential to suppress the indirect effects of CMV infection. This supplement discusses the available data concerning the immunological and clinical effects of CMVIG after heart or lung transplantation.

  9. Clinical applications of intravenous immunoglobulins in neurology

    PubMed Central

    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-01-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain–Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Aβ antibody titres associated with decreased Aβ peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way. PMID:19883422

  10. Efficacy of Intravenous Immunoglobulin in Neurological Diseases.

    PubMed

    Lünemann, Jan D; Quast, Isaak; Dalakas, Marinos C

    2016-01-01

    Owing to its anti-inflammatory efficacy in various autoimmune disease conditions, intravenous immunoglobulin (IVIG)-pooled IgG obtained from the plasma of several thousands individuals-has been used for nearly three decades and is proving to be efficient in a growing number of neurological diseases. IVIG therapy has been firmly established for the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, either as first-line therapy or adjunctive treatment. IVIG is also recommended as rescue therapy in patients with worsening myasthenia gravis and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. Subcutaneous rather than intravenous administration of IgG is gaining momentum because of its effectiveness in patients with primary immunodeficiency and the ease with which it can be administered independently from hospital-based infusions. The demand for IVIG therapy is growing, resulting in rising costs and supply shortages. Strategies to replace IVIG with recombinant products have been developed based on proposed mechanisms that confer the anti-inflammatory activity of IVIG, but their efficacy has not been tested in clinical trials. This review covers new developments in the immunobiology and clinical applications of IVIG in neurological diseases.

  11. Basketball exercise and secretory immunoglobulin A.

    PubMed

    Tharp, G D

    1991-01-01

    This study examined saliva levels of immunoglobulin A (IgA) before and after three games and three practice sessions during the basketball season. Saliva was collected from 27 prepubescent boys (10-12 years) in a small Fry league and 23 postpubescent boys (16-18 years) on a high school varsity team. Saliva samples were frozen for later assay using a standard enzyme-linked immunosorbent assay technique. IgA levels were significantly increased after games 1 and 3 in both age groups and after practice 3 in the high school athletes. Over the 2 months of saliva collections the pre-exercise IgA increased significantly with games 2 and 3 higher than game 1, and practice 3 higher than practices 1 and 2, in both age groups. These results indicate that basketball exercise can increase saliva IgA levels and that chronic exercise over the basketball season may increase the resting levels of IgA. These changes may give athletes more protection against respiratory infections both after exercise and in the resting state later in the season.

  12. Use of subcutaneous immunoglobulin in primary immune deficiencies

    PubMed Central

    Aydıner, Elif Karakoç; Kıykım, Ayça; Barış, Safa; Özen, Ahmet; Barlan, Işıl

    2016-01-01

    Aim: Immunoglobulin replacement therapy is required to reduce the frequency and severity of infections in patients with primary antibody deficiencies. Immunoglobulin G (IgG) can be administered intramuscularly, intravenously or subcutaneously. We aimed to evaluate the efficacy, dose adjustment and adverse events in subcutaneous immunoglobulin therapy by retrospectively presenting the records of 16 patients who received subcutaneous immunoglobulin therapy. Material and Methods: The demographic findings, clinical and laboratory findings, subcutaneous immunoglobulin dosage and dose frequency, infusion time, area and methods, adverse events and frequency of infections were obtained from patient files and recorded. Results: Sixteen patients (seven female, nine male) aged between 0–33 years who were diagnosed with primary immune deficiency and treated with subcutaneous immunoglobulin were enrolled. All patients had been receiving intravenous imunoglobulin (5–10%) at a dose of 0.33–1.25 gr/kg/dose with two-four week intervals before subcutaneous immunoglobulin. Subcutaneous immunoglobulin (10%) was administered at a dose of 0.03–0.43 gr/kg/dose with one-two week intervals. No significant difference was found between serum through IgG levels before administration of intravenous imunoglobulin and steady state IgG levels during subcutaneous immunoglobulin therapy. When five patients whose serum through IgG levels were below 600 mg/dL were evaluated, however, a significant increase was found in steady state IgG levels with subcutaneous immunoglobulin therapy (p=0.043). In a ten-month follow-up period, seven infections were observed in four patients (three upper respiratory infectons, two lower respiratory tract infections and three acute gastroenteritis). No acute severe bacterial infection was observed. Local advers reaction was reported in only 10 of 180 infusions (6%). No serious adverse events were reported. All 16 patients were willing to continue IgG replacement

  13. Applications of intravenous immunoglobulin in haematology.

    PubMed

    Todd, A A; Yap, P L

    1992-06-01

    Intravenous immunoglobulin (IVIgG) has many potential applications in haematology both as antibody replacement therapy and as an immune-modulater in autoimmune disorders. Antibody replacement appears to be of value in the prophylaxis of infection in low-grade B-cell malignancies, in bone marrow transplant recipients and in children with AIDS, although optimal treatment strategies have not been assessed and determining which patients are likely to derive greatest benefit has been problematic. IVIgG appears to be effective in the prevention or amelioration of CMV-related pathology if given frequently and has also dramatically improved the survival of patients with established interstitial pneumonia when used in combination with ganciclovir. Intriguingly, IVIgG appears to moderate the severity of GVHD in adult transplant recipients. IVIgG has short term efficacy in most patients with ITP but, as long term remissions are uncommon, it has become necessary to be more selective in the use of IVIgG in this disorder. The response to IVIgG in other immune-mediated cytopenias is similar with generally transient improvement but also with occasional spectacular cures. The treatment of the acquired haemophilias with IVIgG has yielded in vivo and vitro evidence to support the idiotype-antiidiotype theory of IVIgG immune-modulation and has also demonstrated significant differences in the sensitivity of coagulation factor autoantibodies and alloantibodies to IVIgG therapy. IVIgG has several roles in pregnancy related disorders, including the management of both mother and fetus in ITP during pregnancy, the antenatal and postnatal management of platelet alloimmunisation and also in the management of severe rhesus isoimmunisation. IVIgG is safe and well tolerated. The expense of this therapy should be balanced against the likely gains and the overall costs of alternative approaches.

  14. 7th International Immunoglobulin Conference: Immunomodulation.

    PubMed

    Danieli, M G; Shoenfeld, Y

    2014-12-01

    Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-modifying therapy for RA is methotrexate; however, more than 40 monoclonal antibodies are in use or under investigation for the treatment of RA. This panoply of biological disease-modifying agents means that clinicians can make use of drugs with different mechanisms of action should one type become ineffective. In autoimmune pemphigus conditions, identification of pathogenic autoantibodies against intercellular cadherin desmoglein 1 and/or 3 antigens is one of the criteria for appropriate diagnosis. In pemphigoid conditions, autoantibodies are directed against bullous pemphigoid antigens BP230 and BP180, and in both types of immunobullous disease intravenous immunoglobulin (IVIg), as adjuvant therapy in combination with a cytotoxic drug, is effective in reducing autoantibody levels, disease severity and background steroid use. Further studies are required to establish the role of monoclonal antibodies in the treatment of autoimmune bullous disease. IVIg may also be effective in another at-risk population with autoimmune disease, namely secondary recurrent miscarriage (RM). However, the mechanism of action of IVIg in secondary RM is largely unknown, although levels of natural killer cell biomarkers, particularly CD56(+) , have been shown to decline after IVIg treatment. Data from meta-analyses of heterogeneous placebo-controlled trials indicate that IVIg may be effective in secondary RM, but most trials to date have used immunomodulatory doses lower than those considered to be efficient in autoimmune disease. The results of a recently completed study may help to address this question.

  15. Cloning of immunoglobulin kappa light chain genes from mouse liver and myeloma MOPC 173.

    PubMed

    Steinmetz, M; Zachau, H G; Mach, B

    1979-07-25

    The organization of the kappa chain constant region gene was compared in DNA from an immunoglobulin-producing mouse myeloma (MOPC 173) and from liver. In situ hybridization using the Southern blotting technique revealed constant region gene-containing EcoRI-DNA fragments of 14 and 20 kb in the myeloma tissue whereas one EcoRI-DNA fragment with a length of 15 kb was found in liver DNA. After enrichment by RPC-5 chromatography and preparative electrophoresis the 14 kb fragment from MOPC 173 DNA and the 15 kb fragment from liver DNA were cloned in the bacteriophage lambda vector Charon 4A using in vitro packaging. Extensive characterization of the two fragments by restriction endonuclease mapping, in situ hybridization, and electron microscopy (R-loop and heteroduplex) showed that both fragments contain the constant region but no MOPC 173 variable region gene. Both fragments are homologous over a length of 12.5 kb including the constant region but differ from one another starting about 2.7 kb from the 5' end of the constant region gene. This indicates that the 14 kb EcoRI-DNA fragment from the myeloma tissue clearly resulted from somatic DNA rearrangement although it does not seem to carry the MOPC 173 variable region gene. These observations suggest that somatic DNA rearrangement of immunoglobulin light chain genes can involve both homologous chromosomes.Images

  16. Reevaluation of the role of DNA polymerase theta in somatic hypermutation of immunoglobulin genes.

    PubMed

    Martomo, Stella A; Saribasak, Huseyin; Yokoi, Masayuki; Hanaoka, Fumio; Gearhart, Patricia J

    2008-09-01

    DNA polymerase theta has been implicated in the process of somatic hypermutation in immunoglobulin variable genes based on several reports of alterations in the frequency and spectra of mutations from Polq(-/-) mice. However, these studies have contrasting results on mutation frequencies and the types of nucleotide substitutions, which question the role of polymerase theta in hypermutation. DNA polymerase eta has a dominant effect on mutation and may substitute in the absence of polymerase theta to affect the pattern. Therefore, we have examined mutation in mice deficient for both polymerases theta and eta. The mutation frequencies in rearranged variable genes from Peyer's patches were similar in wild type, Polq(-/-), Polh(-/-), and Polq(-/-)Polh(-/-) mice. The types of substitutions were also similar between wild type and Polq(-/-) clones, and between Polh(-/-) and Polq(-/-)Polh(-/-) clones. Furthermore, there was no difference in heavy chain class switching in splenic B cells from the four groups of mice. These results indicate that polymerase theta does not play a significant role in the generation of somatic mutation in immunoglobulin genes.

  17. Serum Immunoglobulin G4 and Immunoglobulin G1 for Distinguishing Immunoglobulin G4-Associated Cholangitis From Primary Sclerosing Cholangitis

    PubMed Central

    Boonstra, Kirsten; Culver, Emma L; de Buy Wenniger, Lucas Maillette; van Heerde, Marianne J; van Erpecum, Karel J; Poen, Alexander C; van Nieuwkerk, Karin MJ; Spanier, BW Marcel; Witteman, Ben JM; Tuynman, Hans ARE; van Geloven, Nan; van Buuren, Henk; Chapman, Roger W; Barnes, Eleanor; Beuers, Ulrich; Ponsioen, Cyriel Y

    2014-01-01

    The recent addition of immunoglobulin (Ig)G4-associated cholangitis (IAC), also called IgG4-related sclerosing cholangitis (IRSC), to the spectrum of chronic cholangiopathies has created the clinical need for reliable methods to discriminate between IAC and the more common cholestatic entities, primary (PSC) and secondary sclerosing cholangitis. The current American Association for the Study of Liver Diseases practice guidelines for PSC advise on the measurement of specific Ig (sIg)G4 in PSC patients, but interpretation of elevated sIgG4 levels remains unclear. We aimed to provide an algorithm to distinguish IAC from PSC using sIgG analyses. We measured total IgG and IgG subclasses in serum samples of IAC (n = 73) and PSC (n = 310) patients, as well as in serum samples of disease controls (primary biliary cirrhosis; n = 22). sIgG4 levels were elevated above the upper limit of normal (ULN = >1.4 g/L) in 45 PSC patients (15%; 95% confidence interval [CI]: 11-19). The highest specificity and positive predictive value (PPV; 100%) for IAC were reached when applying the 4× ULN (sIgG4 > 5.6 g/L) cutoff with a sensitivity of 42% (95% CI: 31-55). However, in patients with a sIgG4 between 1× and 2× ULN (n = 38/45), the PPV of sIgG4 for IAC was only 28%. In this subgroup, the sIgG4/sIgG1 ratio cutoff of 0.24 yielded a sensitivity of 80% (95% CI: 51-95), a specificity of 74% (95% CI: 57-86), a PPV of 55% (95% CI: 33-75), and a negative predictive value of 90% (95% CI: 73-97). Conclusion: Elevated sIgG4 (>1.4 g/L) occurred in 15% of patients with PSC. In patients with a sIgG4 >1.4 and <2.8 g/L, incorporating the IgG4/IgG1 ratio with a cutoff at 0.24 in the diagnostic algorithm significantly improved PPV and specificity. We propose a new diagnostic algorithm based on IgG4/IgG1 ratio that may be used in clinical practice to distinguish PSC from IAC. (Hepatology 2014;59:1954–1963) PMID:24375491

  18. The Production Processes and Biological Effects of Intravenous Immunoglobulin

    PubMed Central

    Barahona Afonso, Ana Filipa; João, Cristina Maria Pires

    2016-01-01

    Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub-populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production. PMID:27005671

  19. Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones

    PubMed Central

    Plevova, Karla; Francova, Hana Skuhrova; Burckova, Katerina; Brychtova, Yvona; Doubek, Michael; Pavlova, Sarka; Malcikova, Jitka; Mayer, Jiri; Tichy, Boris; Pospisilova, Sarka

    2014-01-01

    In chronic lymphocytic leukemia, usually a monoclonal disease, multiple productive immunoglobulin heavy chain gene rearrangements are identified sporadically. Prognostication of such cases based on immunoglobulin heavy variable gene mutational status can be problematic, especially if the different rearrangements have discordant mutational status. To gain insight into the possible biological mechanisms underlying the origin of the multiple rearrangements, we performed a comprehensive immunogenetic and immunophenotypic characterization of 31 cases with the multiple rearrangements identified in a cohort of 1147 patients with chronic lymphocytic leukemia. For the majority of cases (25/31), we provide evidence of the co-existence of at least two B lymphocyte clones with a chronic lymphocytic leukemia phenotype. We also identified clonal drifts in serial samples, likely driven by selection forces. More specifically, higher immunoglobulin variable gene identity to germline and longer complementarity determining region 3 were preferred in persistent or newly appearing clones, a phenomenon more pronounced in patients with stereotyped B-cell receptors. Finally, we report that other factors, such as TP53 gene defects and therapy administration, influence clonal selection. Our findings are relevant to clonal evolution in the context of antigen stimulation and transition of monoclonal B-cell lymphocytosis to chronic lymphocytic leukemia. PMID:24038023

  20. The Immunobiology of Immunoglobulin G4.

    PubMed

    Lighaam, Laura C; Rispens, Theo

    2016-08-01

    Human immunoglobulin G4 (IgG4) antibodies are in many ways unusual. In this review, an overview is given of the structural and functional aspects of IgG4 antibodies, the consequences of IgG4 antibody formation in various disease settings, and the factors involved in the regulation of IgG4 responses. Unlike most IgG antibodies, IgG4 antibodies exist in a dynamic equilibrium with other IgG4 antibodies, continuously exchanging half-molecules resulting in effectively monovalent antibodies that cannot cross-link. Together with the low affinities to C1q and most Fc receptors, and a generally high affinity for antigen, IgG4 antibodies appear to be nature's way of producing "blocking antibodies." On the one hand, IgG4 may contribute to tolerance to allergens, presumably via competition with IgE. Also, IgG4 immune responses to filarial parasites might prevent excessive immune reactions during such infections. On the other hand, IgG4 autoantibodies may be pathogenic, simply because they inhibit the function of their target molecules. Furthermore, IgG4 antibodies to biologicals may result in secondary loss of response. In addition, IgG4 has been implicated to impair humoral immunity to tumors. The role of high IgG4 serum levels in IgG4-related disease has not yet been established. Regulation of IgG4 responses is most likely a multifactorial process, which in vivo requires prolonged or repeated challenge with antigen, and is associated with regulatory T cells, T helper 2 cells, interleukin- (IL-) 4, and IL-10. In vitro, cytokines like IL-4, IL-13, IL-10, and IL-21 have been shown to differentially influence IgG4 production. The properties of IgG4 B cells have now started to be elucidated, and may provide additional clues to explain the unusual dynamics of IgG4-antibody responses. PMID:27466791

  1. Stress modulates intestinal secretory immunoglobulin A

    PubMed Central

    Campos-Rodríguez, Rafael; Godínez-Victoria, Marycarmen; Abarca-Rojano, Edgar; Pacheco-Yépez, Judith; Reyna-Garfias, Humberto; Barbosa-Cabrera, Reyna Elizabeth; Drago-Serrano, Maria Elisa

    2013-01-01

    Stress is a response of the central nervous system to environmental stimuli perceived as a threat to homeostasis. The stress response triggers the generation of neurotransmitters and hormones from the hypothalamus pituitary adrenal axis, sympathetic axis and brain gut axis, and in this way modulates the intestinal immune system. The effects of psychological stress on intestinal immunity have been investigated mostly with the restraint/immobilization rodent model, resulting in an up or down modulation of SIgA levels depending on the intensity and time of exposure to stress. SIgA is a protein complex formed by dimeric (dIgA) or polymeric IgA (pIgA) and the secretory component (SC), a peptide derived from the polymeric immunoglobulin receptor (pIgR). The latter receptor is a transmembrane protein expressed on the basolateral side of gut epithelial cells, where it uptakes dIgA or pIgA released by plasma cells in the lamina propria. As a result, the IgA-pIgR complex is formed and transported by vesicles to the apical side of epithelial cells. pIgR is then cleaved to release SIgA into the luminal secretions of gut. Down modulation of SIgA associated with stress can have negative repercussions on intestinal function and integrity. This can take the form of increased adhesion of pathogenic agents to the intestinal epithelium and/or an altered balance of inflammation leading to greater intestinal permeability. Most studies on the molecular and biochemical mechanisms involved in the stress response have focused on systemic immunity. The present review analyzes the impact of stress (mostly by restraint/immobilization, but also with mention of other models) on the generation of SIgA, pIgR and other humoral and cellular components involved in the intestinal immune response. Insights into these mechanisms could lead to better therapies for protecting against pathogenic agents and avoiding epithelial tissue damage by modulating intestinal inflammation. PMID:24348350

  2. Properties and mechanisms of immunoglobulins for congenital cytomegalovirus disease.

    PubMed

    Parruti, Giustino; Polilli, Ennio; Ursini, Tamara; Tontodonati, Monica

    2013-12-01

    Immunoglobulins are one major component of adaptive immunity to external and resident microorganisms, evolving very early in phylogenesis. They help eukaryotes in controlling infections, mainly through their neutralizing activity, which quenches both the cytopathic and inflammatory potential of invading microorganisms. Cytomegalovirus (CMV)-related disease is generally blunted in seropositive subjects with conserved specific humoral responses. CMV-seropositive pregnant women, in accordance with such evidence, suffer little or no fetal damage when reexposed to CMV. Several seminal experiences and early experimental models confirmed that repeated infusions of immunoglobulins, either with hyperimmune or standard preparations, may help to reduce maternal-fetal CMV transmission, as well as to quench fetal disease upon transmission. This review focused on experimental evidence supporting the potential role of immunoglobulins as a tool to control fetal CMV-related disease in pregnant women.

  3. FUNDAMENTAL DIFFERENCES BETWEEN NATURAL ANTIBODIES AND POLYREACTIVE IMMUNOGLOBULINS.

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2015-01-01

    A problem of similarity and differences between so-called polyreactive immunoglobulins (PRIGs) and natural antibodies (NAbs), capable of cross-reacting with some structurally dissimilar antigens, has been considered. The analysis of mechanisms of an unspecific interaction between PRIGs or NAbs and antigens evidences for the fact that essential differences exist between these substances. These differences permit classifying the abovementioned substances as different types of immunoglobulin molecules. The major difference between PRIGs and NAbs may include both the mechanisms of the above mentioned immunoglobulin molecules binding to antigens and their interaction affinity, as well as an absolutely different influence of some low-molecular substances on the efficiency of the interaction with antigens. Relying on the obtained data it can be assumed that, since PRIGs and NAbs have fundamental differences, they may perform not only similar but also different functions of the immune system.

  4. Non-immune immunoglobulins shield Schistosoma japonicum from host immunorecognition

    PubMed Central

    Wu, Chuang; Hou, Nan; Piao, Xianyu; Liu, Shuai; Cai, Pengfei; Xiao, Yan; Chen, Qijun

    2015-01-01

    Schistosomiasis is a major human parasitic disease with a global impact. Schistosoma japonicum, the most difficult to control, can survive within host veins for decades. Mechanisms of immune evasion by the parasite, including antigenic variation and surface masking, have been implicated but not well defined. In this study, we defined the immunoglobulin-binding proteomes of S. japonicum using human IgG, IgM, and IgE as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Several proteins situated at the tegument of S. japonicum were able to nonselectively bind to the Fc domain of host immunoglobulins, indicating a mechanism for the avoidance of host immune attachment and recognition. The profile of the immunoglobulin-binding proteomes provides further clues for immune evasion mechanisms adopted by S. japonicum. PMID:26299686

  5. Targeting of AID-mediated sequence diversification to immunoglobulin genes.

    PubMed

    Kothapalli, Naga Rama; Fugmann, Sebastian D

    2011-04-01

    Activation-induced cytidine deaminase (AID) is a key enzyme for antibody-mediated immune responses. Antibodies are encoded by the immunoglobulin genes and AID acts as a transcription-dependent DNA mutator on these genes to improve antibody affinity and effector functions. An emerging theme in field is that many transcribed genes are potential targets of AID, presenting an obvious danger to genomic integrity. Thus there are mechanisms in place to ensure that mutagenic outcomes of AID activity are specifically restricted to the immunoglobulin loci. Cis-regulatory targeting elements mediate this effect and their mode of action is probably a combination of immunoglobulin gene specific activation of AID and a perversion of faithful DNA repair towards error-prone outcomes.

  6. Gut immunity in a protochordate involves a secreted immunoglobulin-type mediator binding host chitin and bacteria

    PubMed Central

    Dishaw, Larry J.; Leigh, Brittany; Cannon, John P.; Liberti, Assunta; Mueller, M. Gail; Skapura, Diana P.; Karrer, Charlotte R.; Pinto, Maria R.; De Santis, Rosaria; Litman, Gary W.

    2016-01-01

    Protochordate variable region-containing chitin-binding proteins (VCBPs) consist of immunoglobulin-type V domains and a chitin-binding domain (CBD). VCBP V domains facilitate phagocytosis of bacteria by granulocytic amoebocytes; the function of the CBD is not understood. Here we show that the gut mucosa of Ciona intestinalis contains an extensive matrix of chitin fibrils to which VCBPs bind early in gut development, before feeding. Later in development, VCBPs and bacteria colocalize to chitin-rich mucus along the intestinal wall. VCBP-C influences biofilm formation in vitro and, collectively, the findings of this study suggest that VCBP-C may influence the overall settlement and colonization of bacteria in the Ciona gut. Basic relationships between soluble immunoglobulin-type molecules, endogenous chitin and bacteria arose early in chordate evolution and are integral to the overall function of the gut barrier. PMID:26875669

  7. Gut immunity in a protochordate involves a secreted immunoglobulin-type mediator binding host chitin and bacteria.

    PubMed

    Dishaw, Larry J; Leigh, Brittany; Cannon, John P; Liberti, Assunta; Mueller, M Gail; Skapura, Diana P; Karrer, Charlotte R; Pinto, Maria R; De Santis, Rosaria; Litman, Gary W

    2016-01-01

    Protochordate variable region-containing chitin-binding proteins (VCBPs) consist of immunoglobulin-type V domains and a chitin-binding domain (CBD). VCBP V domains facilitate phagocytosis of bacteria by granulocytic amoebocytes; the function of the CBD is not understood. Here we show that the gut mucosa of Ciona intestinalis contains an extensive matrix of chitin fibrils to which VCBPs bind early in gut development, before feeding. Later in development, VCBPs and bacteria colocalize to chitin-rich mucus along the intestinal wall. VCBP-C influences biofilm formation in vitro and, collectively, the findings of this study suggest that VCBP-C may influence the overall settlement and colonization of bacteria in the Ciona gut. Basic relationships between soluble immunoglobulin-type molecules, endogenous chitin and bacteria arose early in chordate evolution and are integral to the overall function of the gut barrier. PMID:26875669

  8. Identification of Immunoglobulin Gene Sequences from a Small Read Number of mRNA-Seq Using Hybridomas

    PubMed Central

    Iwasaki, Takeshi; Hayashi, Masayasu; Semba, Yuichiro; Fujita, Masatoshi; Sato, Yuko; Kimura, Hiroshi; Harada, Akihito

    2016-01-01

    Identification of immunoglobulin genes in hybridomas is essential for producing antibodies for research and clinical applications. A couple of methods such as RACE and degenerative PCR have been developed for determination of the Igh and Igl/Igk coding sequences (CDSs) but it has been difficult to process a number of hybridomas both with accuracy and rapidness. Here, we propose a new strategy for antibody sequence determination by mRNA-seq of hybridomas. We demonstrated that hybridomas highly expressed the Igh and Igl/Igk genes and that de novo transcriptome assembly using mRNA-seq data enabled identification of the CDS of both Igh and Igl/Igk accurately. Furthermore, we estimated that only 30,000 sequenced reads are required to identify immunoglobulin sequences from four different hybridoma clones. Thus, our approach would facilitate determining variable CDSs drastically. PMID:27788226

  9. The immunoglobulin-like genetic predetermination of the brain: the protocadherins, blueprint of the neuronal network

    NASA Astrophysics Data System (ADS)

    Hilschmann, N.; Barnikol, H. U.; Barnikol-Watanabe, S.; Götz, H.; Kratzin, H.; Thinnes, F. P.

    2001-01-01

    The morphogenesis of the brain is governed by synaptogenesis. Synaptogenesis in turn is determined by cell adhesion molecules, which bridge the synaptic cleft and, by homophilic contact, decide which neurons are connected and which are not. Because of their enormous diversification in specificities, protocadherins (pcdhα, pcdhβ, pcdhγ), a new class of cadherins, play a decisive role. Surprisingly, the genetic control of the protocadherins is very similar to that of the immunoglobulins. There are three sets of variable (V) genes followed by a corresponding constant (C) gene. Applying the rules of the immunoglobulin genes to the protocadherin genes leads, despite of this similarity, to quite different results in the central nervous system. The lymphocyte expresses one single receptor molecule specifically directed against an outside stimulus. In contrast, there are three specific recognition sites in each neuron, each expressing a different protocadherin. In this way, 4,950 different neurons arising from one stem cell form a neuronal network, in which homophilic contacts can be formed in 52 layers, permitting an enormous number of different connections and restraints between neurons. This network is one module of the central computer of the brain. Since the V-genes are generated during evolution and V-gene translocation during embryogenesis, outside stimuli have no influence on this network. The network is an inborn property of the protocadherin genes. Every circuit produced, as well as learning and memory, has to be based on this genetically predetermined network. This network is so universal that it can cope with everything, even the unexpected. In this respect the neuronal network resembles the recognition sites of the immunoglobulins.

  10. Identification of the ancestral killer immunoglobulin-like receptor gene in primates

    PubMed Central

    Sambrook, Jennifer G; Bashirova, Arman; Andersen, Hanne; Piatak, Mike; Vernikos, George S; Coggill, Penny; Lifson, Jeff D; Carrington, Mary; Beck, Stephan

    2006-01-01

    Background Killer Immunoglobulin-like Receptors (KIR) are essential immuno-surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear. Results Using comparative analyses, we have identified the ancestral KIR lineage (provisionally named KIR3DL0) in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human (Homo sapiens), common chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla), rhesus monkey (Macaca mulatta) and common marmoset (Callithrix jacchus). We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells. Conclusion One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution. PMID:16911775

  11. Beswitched. The looping out model for immunoglobulin class switching.

    PubMed

    von Schwedler, U; Jäck, H M; Wabl, M

    1990-08-01

    During the switch in expression of an immunoglobulin class, the gene segment encoding the constant region of the heavy chain is replaced in a way that leads to a deletion. Three different models of how this deletion is generated have been proposed: recombination between homologs, unequal sister chromatid exchange, and looping out and deletion. While none of the predicted recombination products of the first two models have been found, the products of the looping out--inversions and circular DNA--have been isolated. Thus looping out and deletion appears to be the appropriate model to explain the genetic events leading to the immunoglobulin heavy chain class switch. PMID:2282364

  12. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement of immunoglobulin G Fd fragments aids in the diagnosis of plasma antibody-forming cell abnormalities....

  13. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fab fragment specific... Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system. (a) Identification. An immunoglobulin G (Fab fragment specific) immunological test system is a device that...

  14. Effects of sample collection and storage methods on antipneumococcal immunoglobulin A in saliva.

    PubMed

    Nurkka, A; Obiero, J; Käyhty, H; Scott, J A G

    2003-05-01

    Saliva contains components of both the mucosal and systemic immune systems. Variable flow rates, immunoglobulin proteases, and variation in collection and storage methods all introduce differences in the estimated concentrations of antibodies. We evaluated the effect of four collection methods and three storage protocols on the concentrations of immunoglobulin A (IgA) antibodies to pneumococcal capsular antigens 1, 5, 6B, and 14 and to pneumococcal surface adhesin A (PsaA) in saliva. Specimens were collected from 30 healthy Kenyan adults by collecting drool, by pipette suction, and with two commercial kits, OraSure and Oracol. Aliquots from each specimen were snap-frozen with glycerol in liquid nitrogen or stored for 4 to 8 h at +4 degrees C either with or without the addition of protease enzyme inhibitors prior to storage at -70 degrees C. Anticapsular IgA concentrations were not significantly different with different collection methods, but snap-freezing the specimens in liquid nitrogen led to concentrations 41 to 47% higher than those of specimens stored by the other methods (P < 0.0005).

  15. Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy.

    PubMed

    Muchtar, Eli; Buadi, Francis K; Dispenzieri, Angela; Gertz, Morie A

    2016-01-01

    Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.

  16. Leporid immunoglobulin G shows evidence of strong selective pressure on the hinge and CH3 domains

    PubMed Central

    Pinheiro, Ana; Woof, Jenny M.; Almeida, Tereza; Abrantes, Joana; Alves, Paulo C.; Gortázar, Christian; Esteves, Pedro J.

    2014-01-01

    Immunoglobulin G (IgG) is the predominant serum immunoglobulin and has the longest serum half-life of all the antibody classes. The European rabbit IgG has been of significant importance in immunological research, and is therefore well characterized. However, the IgG of other leporids has been disregarded. To evaluate the evolution of this gene in leporids, we sequenced the complete IGHG for six other genera: Bunolagus, Brachylagus, Lepus, Pentalagus, Romerolagus and Sylvilagus. The newly sequenced leporid IGHG gene has an organization and structure similar to that of the European rabbit IgG. A gradient in leporid IgG constant domain diversity was observed, with the CH1 being the most conserved and the CH3 the most variable domain. Positive selection was found to be acting on all constant domains, but with a greater incidence in the CH3 domain, where a cluster of three positively selected sites was identified. In the hinge region, only three polymorphic positions were observed. The same hinge length was observed for all leporids. Unlike the variation observed for the European rabbit, all 11 Lepus species studied share exactly the same hinge motif, suggesting its maintenance as a result of an advantageous structure or conformation. PMID:25185680

  17. Secondary Rearrangements and Hypermutation Generate Sufficient B Cell Diversity to Mount Protective Antiviral Immunoglobulin Responses

    PubMed Central

    López-Macías, Constantino; Kalinke, Ulrich; Cascalho, Marilia; Wabl, Matthias; Hengartner, Hans; Zinkernagel, Rolf M.; Lamarre, Alain

    1999-01-01

    Variable (V) region gene replacement was recently implicated in B cell repertoire diversification, but the contribution of this mechanism to antibody responses is still unknown. To investigate the role of V gene replacements in the generation of antigen-specific antibodies, we analyzed antiviral immunoglobulin responses of “quasimonoclonal” (QM) mice. The B cells of QM mice are genetically committed to exclusively express the anti-(4-hydroxy-3-nitrophenyl) acetyl specificity. However, ∼20% of the peripheral B cells of QM mice undergo secondary rearrangements and thereby potentially acquire new specificities. QM mice infected with vesicular stomatitis virus (VSV), lymphocytic choriomeningitis virus, or poliovirus mounted virus-specific neutralizing antibody responses. In general, kinetics of the antiviral immunoglobulin responses were delayed in QM mice; however, titers similar to control animals were eventually produced that were sufficient to protect against VSV-induced lethal disease. VSV neutralizing single-chain Fv fragments isolated from phage display libraries constructed from QM mice showed VH gene replacements and extensive hypermutation. Thus, our data demonstrate that secondary rearrangements and hypermutation can generate sufficient B cell diversity in QM mice to mount protective antiviral antibody responses, suggesting that these mechanisms might also contribute to the diversification of the B cell repertoire of normal mice. PMID:10359583

  18. Studies on the quantitation of immunoglobulin in human intestinal secretions

    PubMed Central

    Samson, R. R.; McClelland, D. B. L.; Shearman, D. J. C.

    1973-01-01

    There is increasing evidence for the importance of the secretory immune system in the gut. In studies of local antibody production it is important to have satisfactory methods for measuring immunoglobulin concentrations and to be aware of the errors which may occur. Studies on immunoglobulin measurement in intestinal secretion by the radial immunodiffusion method are reported, showing the effects of proteolytic digestion, IgA molecular size, and sampling and storage conditions. Because of the presence of monomeric IgA in addition to secretory IgA, there is no satisfactory standard for IgA in gastrointestinal secretions, and only semi-quantitative results can be given. With radial immunodiffusion, IgG and IgM when subjected to tryptic digestion, and IgA when subjected to peptic digestion, may be overestimated because of the presence of fragments of immunoglobulins. In addition, pepsin rapidly destroys IgM and IgG. Both IgM and IgG are unstable in storage. The findings suggest that immunoglobulin concentration measurements in small intestinal aspirates should be interpreted with caution. These problems are also relevant to the detection of specific antibodies in gastrointestinal secretions. ImagesFig 3Fig 5Fig 7Fig 8Fig 9Fig 11 PMID:4582728

  19. Intravenous Immunoglobulin in the Treatment of Severe Clostridium Difficile Colitis

    PubMed Central

    Shah, Nihar; Shaaban, Hamid; Spira, Robert; Slim, Jihad; Boghossian, Jack

    2014-01-01

    Intravenous immunoglobulin (IVIG) has been utilized in patients with recurrent and refractory Clostridium difficile colitis. It is increasingly being used in patients with initial clinical presentation of severe colitis. Herein, we report a case of severe C. Difficile colitis successfully treated with IVIG with a review of the medical literature to identify the optimal timing and clinical characteristics for this treatment strategy. PMID:24926170

  20. Adult Fanconi syndrome with monoclonal abnormality of immunoglobulin light chain

    PubMed Central

    Harrison, J. F.; Blainey, J. D.

    1967-01-01

    Two adult cases of the Fanconi syndrome are described, in each of which there was abnormal urinary excretion of immunoglobulin κ-chain. The significance of this finding is discussed in relation to the recognized association between multiple myeloma and the Fanconi syndrome. Images PMID:6016886

  1. Immunoglobulin genes: generating diversity with AID and UNG.

    PubMed

    Storb, Ursula; Stavnezer, Janet

    2002-10-29

    Somatic hypermutation and switch recombination of immunoglobulin genes require the activity of the activation-induced deaminase, AID. Recent studies of mice deficient for the uracil-DNA glycosylase UNG, which removes U from DNA, suggest that AID catalyses the deamination of dC to dU during antibody diversification.

  2. [Clinical significance of analysis of immunoglobulin A levels in saliva].

    PubMed

    Bokor-Bratić, M

    2000-01-01

    SALIVA COLLECTION: Whole saliva is a product of secretion of 3 major glands (parotid, submandibular, sublingual) and many minor glands (labial, buccal, palatal). Unstimulated saliva is usually obtained as the patient spits out every 60 sec. or by forward bended head the patient allows saliva to drip off the lower lip into a cylinder. By collection of saliva in the tube the flow rate per unit time can be measured. When volume measurement is not required the saliva can be collected on cotton rolls, gauze or filter paper. For evaluating salivary gland function or when large volumes of saliva are required for analytic purposes, stimulated whole saliva is used. Method of collection is the same as for unstimulated saliva. The usual masticatory stimuli are paraffin wax or a washed rubber band. A standard gustatory stimulus is obtained by 2% citric acid applied directly to the tongue every 15 to 60 sec. Parotid saliva can be collected by aspiration from the duct opening with a micropipette. Parotid saliva is best collected with Lashley's vacuum chamber. Submandibular and sublingual saliva can be collected by cannulation of the duct with micropipette, but in practice this is both uncomfortable for the patients and technically difficult since the duct orifice is mobile and has a strong sphincter. Because of that, alginate and silicone impression material is used for retention of the collecting tube. As alternative and simple technique is to block off secretion from the parotid glands with absorbent swabs and collect mixed submandibular and sublingual saliva by pipette from the floor of the mouth. Saliva from labial and palatal glands can be collected by filter paper disc or disc of other synthetic materials. SALIVARY IMMUNOGLOBULIN A: The most significant characteristics of the salivary immunoglobulin system are quantitative domination of immunoglobulin A, local synthesis and specific structure. Immunofluorescence studies have shown that immunoglobulin A is produced by

  3. [Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].

    PubMed

    Zenita, K; Yago, K; Fujimoto, E; Kannagi, R

    1990-07-01

    We investigated the immunoglobulin genes which encode the variable region of the monoclonal antibodies directed to the onco-developmental carbohydrate antigens such SSEA-1, fucosyl SSEA-1, SSEA-3 and SSEA-4. The VH region of these antibodies was preferentially encoded by the gene members of the X24, VH7183 and Q52 families, the families which are known to be located at the 3'-end region of the murine germ line VH gene. This result is interesting particularly when considering that the members of the 3'-end VH families are known to be preferentially expressed in embryonic B lymphocytes by an intrinsic genetic program. The comparative study of the nucleic acid sequences of mRNAs encoding these antibodies and the sequences of the corresponding germ line VH genes disclosed that the sequences encoding the antibodies contain no mutation from the germ line VH genes, or contain only a few somatic mutations, which are thought to be insignificant for the reactivity of the antibodies to the nominal antigens. These results imply that some of the embryonic B lymphocytes that express the unmutated germ line VH genes of the 3'-end families can be reactive with embryonic carbohydrate antigens, albeit rearranged with appropriate D-JH gene segments, and coupled with proper light chains. The VH region of the syngenic monoclonal anti-idiotypic antibodies directed to these anti-carbohydrate antibodies were also encoded preferentially by the members of the 3'-end VH families. We propose here that a part of the virgin embryonic B lymphocytes, which express the antibody encoded by the gene members of the 3'-end VH families at the cell surface, will be stimulated by the embryonic carbohydrate antigens which are abundantly present in the internal milieu of the embryo. The clonally expanded B lymphocytes, in turn, will facilitate the proliferation of other populations of embryonic B lymphocytes expressing the corresponding anti-idiotypic antibodies, which are also encoded by the gene members

  4. Common Variable Immunodeficiency.

    PubMed

    Saikia, Biman; Gupta, Sudhir

    2016-04-01

    Common variable immunodeficiency (CVID) is the most common primary immunodeficiency of young adolescents and adults which also affects the children. The disease remains largely under-diagnosed in India and Southeast Asian countries. Although in majority of cases it is sporadic, disease may be inherited in a autosomal recessive pattern and rarely, in autosomal dominant pattern. Patients, in addition to frequent sino-pulmonary infections, are also susceptible to various autoimmune diseases and malignancy, predominantly lymphoma and leukemia. Other characteristic lesions include lymphocytic and granulomatous interstitial lung disease, and nodular lymphoid hyperplasia of gut. Diagnosis requires reduced levels of at least two immunoglobulin isotypes: IgG with IgA and/or IgM and impaired specific antibody response to vaccines. A number of gene mutations have been described in CVID; however, these genetic alterations account for less than 20% of cases of CVID. Flow cytometry aptly demonstrates a disturbed B cell homeostasis with reduced or absent memory B cells and increased CD21(low) B cells and transitional B cell populations. Approximately one-third of patients with CVID also display T cell functional defects. Immunoglobulin therapy remains the mainstay of treatment. Immunologists and other clinicians in India and other South East Asian countries need to be aware of CVID so that early diagnosis can be made, as currently, majority of these patients still go undiagnosed. PMID:26868026

  5. Mucosal immunoglobulins and B cells of Teleost fish

    PubMed Central

    Salinas, Irene; Zhang, Yong-An; Sunyer, J. Oriol

    2012-01-01

    As physical barriers that separate teleost fish from the external environment, mucosae are also active immunological sites that protect them against exposure to microbes and stressors. In mammals, the sites where antigens are sampled from mucosal surfaces and where stimulation of naive T and B lymphocytes occurs are known as inductive sites and are constituted by mucosa-associated lymphoid tissue (MALT). According to anatomical location, the MALT in teleost fish is subdivided into gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), and gill-associated lymphoid tissue (GIALT). All MALT contain a variety of leukocytes, including, but not limited to, T cells, B cells, plasma cells, macrophages and granulocytes. Secretory immunoglobulins are produced mainly by plasmablasts and plasma cells, and play key roles in the maintenance of mucosal homeostasis. Until recently, teleost fish B cells were thought to express only two classes of immunoglobulins, IgM and IgD, in which IgM was thought to be the only one responding to pathogens both in systemic and mucosal compartments. However, a third teleost immunoglobulin class, IgT/IgZ, was discovered in 2005, and it has recently been shown to behave as the prevalent immunoglobulin in gut mucosal immune responses. The purpose of this review is to summarise the current knowledge of mucosal immunoglobulins and B cells of fish MALT. Moreover, we attempt to integrate the existing knowledge on both basic and applied research findings on fish mucosal immune responses, with the goal to provide new directions that may facilitate the development of novel vaccination strategies that stimulate not only systemic, but also mucosal immunity. PMID:22133710

  6. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection

    PubMed Central

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMappTM and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. PMID:27067649

  7. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection.

    PubMed

    Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu

    2016-01-01

    Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab')2 fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab')2 at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs.

  8. Ability to develop broadly neutralizing HIV-1 antibodies is not restricted by the germline immunoglobulin gene repertoire1

    PubMed Central

    Scheepers, Cathrine; Shrestha, Ram K.; Lambson, Bronwen E.; Jackson, Katherine J. L.; Wright, Imogen A.; Naicker, Dshanta; Goosen, Mark; Berrie, Leigh; Ismail, Arshad; Garrett, Nigel; Karim, Quarraisha Abdool; Karim, Salim S. Abdool; Moore, Penny L.; Travers, Simon A.; Morris, Lynn

    2015-01-01

    The human immunoglobulin repertoire is vast, producing billions of unique antibodies from a limited number of germline immunoglobulin genes. The immunoglobulin heavy chain variable region (IGHV) is central to antigen binding and is comprised of 48 functional genes. Here we analyzed whether HIV-1 infected individuals who develop broadly neutralizing antibodies show a distinctive germline IGHV profile. Using both 454 and Illumina technologies we sequenced the IGHV repertoire of 28 HIV-infected South African women from the Center for the AIDS Programme of Research in South African (CAPRISA) 002 and 004 cohorts, 13 of whom developed broadly neutralizing antibodies. Of the 259 IGHV alleles identified in this study, approximately half were not found in the International Immunogenetics Database (IMGT). This included 85 entirely novel alleles and 38 alleles that matched rearranged sequences in non-IMGT databases. Analysis of the rearranged H chain V region genes of monoclonal antibodies isolated from 7 of the CAPRISA women and previously isolated broadly neutralizing antibodies from other donors provided evidence that at least 8 novel or non-IMGT alleles contributed to functional antibodies. Importantly, we found that despite a wide range in the number of IGHV alleles in each individual, including alleles used by known broadly neutralizing antibodies, there were no significant differences in germline IGHV repertoires between individuals who do and do not develop broadly neutralizing antibodies. This study reports novel IGHV repertoires and highlights the importance of a fully comprehensive immunoglobulin database for germline gene usage prediction. Furthermore, these data suggest a lack of genetic bias in broadly neutralizing antibody development in HIV-1 infection, with implications for HIV vaccine design. PMID:25825450

  9. Comparison of techniques of detecting immunoglobulin-binding protein reactivity to immunoglobulin produced by different avian and mammalian species.

    PubMed

    Justiz-Vaillant, A A; Akpaka, P E; McFarlane-Anderson, N; Smikle, M F

    2013-01-01

    The rationale of this study was to use several immunological assays to investigate the reactivity of immunoglobulin binding protein (IBP) to immunoglobulins from various avian and mammalian species. The IBP studied were Staphylococcal protein A (SpA), Streptococcal protein G (SpG), Peptostreptococcal protein L (SpL) and recombinant protein LA (SpLA). The various immunological techniques used were double immunodiffusion (Ouchterlony technique) that tested positive high protein reactivities, direct and competitive enzyme-linked immunosorbent assays (ELISAs) that tested moderate and low positive protein binding capacities, respectively. In addition to sandwich ELISAs, immunoblot analyses and Ig-purification by SpA-affinity chromatography, which were sensitive tests and helpful in the screening and confirmatory tests were also used. The Ouchterlony technique showed that compared to the other proteins, SpLA had the highest range of reactivity with animal sera and purified immunoglobulins while SpL was least reactive. With the direct ELISA, SpL reacted with the raccoon sera, rabbit IgG and with IgY from bantam hens and pigeons. While with the direct ELISA, SpA reacted with sera from skunk, coyote, raccoon, mule, donkey and human. The sandwich ELISA revealed high reactivity of both SpG and SpLA with mammalian sera titres ranging from 1:32 (raccoon serum) to 1:1024 (mule and donkey sera). These results suggest that IBP can be used for the detection of immunoglobulin using various immunological assays and this is important for the diagnosis of infectious diseases in animal and bird populations studied and in the purification of immunoglobulins. PMID:24171322

  10. Intravenous Immunoglobulins: Mode of Action and Indications in Autoimmune and Inflammatory Dermatoses

    PubMed Central

    Dourmishev, Lyubomir A.; Guleva, Dimitrina V.; Miteva, Ljubka G.

    2016-01-01

    Intravenous immunoglobulins (IVIGs), a mixture of variable amounts of proteins (albumin, IgG, IgM, IgA, and IgE antibodies), as well as salt, sugar, solvents, and detergents, are successfully used to treat a variety of dermatological disorders. For decades, IVIGs have been administered for treatment of infectious diseases and immune deficiencies, since they contain natural antibodies that represent a first-line defense against pathogens. Today their indication has expanded, including the off-label therapy for a variety of autoimmune and inflammatory diseases. In dermatology, IVIGs are administered for treatment of different disorders at different therapeutic regimens, mostly with higher doses then those administered for treatment of infectious diseases. The aim of this prospective review is to highlight the indications, effectiveness, side effects, and perspectives of the systemic treatment with IVIGs for patients with severe, life-threatening, and resistant to conventional therapies autoimmune or inflammatory dermatoses. PMID:26885437

  11. Dependence of Enhancer-Mediated Transcription of the Immunoglobulin μ Gene on Nuclear Matrix Attachment Regions

    NASA Astrophysics Data System (ADS)

    Forrester, William C.; van Genderen, Courtney; Jenuwein, Thomas; Grosschedl, Rudolf

    1994-08-01

    Transcription of the immunoglobulin μ heavy chain locus is regulated by an intronic enhancer that is flanked on both sides by nuclear matrix attachment regions (MARs). These MARs have now been shown to be essential for transcription of a rearranged μ gene in transgenic B lymphocytes, but they were not required in stably transfected tissue culture cells. Normal rates of transcriptional initiation at a variable region promoter and the formation of an extended deoxyribonuclease I (DNase I)-sensitive chromatin domain were dependent on MARs, although DNase I hypersensitivity at the enhancer was detected in the absence of MARs. Thus, transcriptional activation of the μ gene during normal lymphoid development requires a synergistic collaboration between the enhancer and flanking MARs.

  12. Highly conforming polyethylene inlays reduce the in vivo variability of knee joint kinematics after total knee arthroplasty.

    PubMed

    Daniilidis, Kiriakos; Skwara, Adrian; Vieth, Volker; Fuchs-Winkelmann, Susanne; Heindel, Walter; Stückmann, Volker; Tibesku, Carsten O

    2012-08-01

    The use of highly conforming polyethylene inlays in total knee arthroplasty (TKA) provides improved anteroposterior stability. The aim of this fluoroscopic study was to investigate the in vivo kinematics during unloaded and loaded active extension with a highly conforming inlay and a flat inlay after cruciate retaining (CR) total knee arthroplasty (TKA). Thirty one patients (50 knees) received a fixed-bearing cruciate retaining total knee arthroplasty (Genesis II, Smith & Nephew, Schenefeld, Germany) for primary knee osteoarthritis. Twenty two of them received a flat polyethylene inlay (PE), nine a deep dished PE and 19 were in the control group (physiological knees). The mean age at the time of surgery was 62 years. Dynamic examination with fluoroscopy was performed to assess the "patella tendon angle" in relation to the knee flexion angle (measure of anteroposterior translation) and the "kinematic index" (measure of reproducibility). Fluoroscopy was performed under active extension and flexion, during unloaded movement, and under full weight bearing, simulated by step climbing. No significant difference was observed between both types of polyethylene inlay designs and the physiological knee during unloaded movement. Anteroposterior (AP) instability was found during weight-bearing movement. The deep-dish inlay resulted in lower AP translation and a non-physiological rollback. Neither inlay types could restore physiological kinematics of the knee. Despite the fact that deep dished inlays reduce the AP translation, centralisation of contact pressure results in non-physiological rollback. The influence of kinematic pattern variability on clinical results warrants further investigation.

  13. [Immunoglobulins or plasma exchange? Guillain-Barré syndrome: indications for plasma exchange and immunoglobulins].

    PubMed

    Raphaël, J C; Chevret, S; Jars-Guincestre, M C; Chastang, C; Gajdos, P

    1993-01-01

    The effect of plasma exchange (PE) in the Guillain-Barré syndrome (GBS) has been evaluated in 4 randomized clinical trials. A positive effect could be excluded in only one study conducted in Great Britain which included 29 patients. The more powerful studies conducted in Sweden (39 patients), in North America (245 patients) and in France (220 patients) demonstrated that early use of four PEs in patients with a GBS severe enough to require assistance in walking was followed by decreased duration and severity of the acute phase. These conclusions were ratified at a North American consensus conference. More recently, PE has been demonstrated to increase the number of patients who recover normal muscular power after a 1-year follow-up. The French trial also demonstrated that diluted albumin should be preferred over fresh frozen plasma. The number of plasma exchanges and the role of PE in initially benign forms is of great importance and is now under study by a cooperative group in France. The effect of immunoglobulins (IgG) was recently investigated in a randomized trial including 150 patients. In this study, high doses (0.4 g/kg/day for 5 days) were compared with 5 PE administered between days 7 and 14 in children and adults who, at inclusion, were unable to walk. The main result was that the outcome at one month was good with IgG as with PE. Treatment is easier with IgG, and morbidity is lower. Direct costs are similar. If IgG are shown to be as effective as PE, IgG should be given for GBS.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. [The role of immunoglobulin preparations in treatment of allergic diseases].

    PubMed

    Boznański, Andrzej; Widerska, Alicja

    2002-01-01

    Intravenous immunoglobulin (IVIG) has been used for many years to treat patients with primary immunodeficiencies. More recently, IVIG has been shown to have antiinflammatory activity when used at substantially higher concentrations. A number of studies have examined the efficacy of IVIG in allergic diseases. For patients with severe refractory asthma, sinusitis, atopic dermatitis, and urticaria, IVIG offers an alternative therapy with relatively few side effects. Although the mechanism by which IVIG may attenuate the allergic response is still undetermined, clinical studies have shown that immunoglobulin therapy can decrease serum IgE levels and increase glucocorticoid binding affinity, while in vitro studies have shown that IVIG can decrease T-cell secretion of TH2 cytokines.

  15. Dual immunoglobulin light chain B cells: Trojan horses of autoimmunity?

    PubMed

    Pelanda, Roberta

    2014-04-01

    Receptor editing, a major mechanism of B cell tolerance, can also lead to allelic inclusion at the immunoglobulin light chain loci and the development of B cells that coexpress two different immunoglobulin light chains and, therefore, two antibody specificities. Most allelically included B cells express two κ chains, although rare dual-λ cells are also observed. Moreover, these cells typically coexpress an autoreactive and a nonautoreactive antibody. Thus, allelically included B cells could operate like 'Trojan horses': expression and function of the nonautoreactive antigen receptors might promote their maturation, activation, and terminal differentiation into effector cells that also express and secrete autoantibodies. Indeed, dual-κ B cells are greatly expanded into effector B cell subsets in some autoimmune mice, thus indicating they might play an important role in disease.

  16. Intravenous Immunoglobulin in the Management of Lupus Nephritis

    PubMed Central

    Wenderfer, Scott E.; Thacker, Trisha

    2012-01-01

    The occurrence of nephritis in patients with systemic lupus erythematosus is associated with increased morbidity and mortality. The pathogenesis of lupus nephritis is complex, involving innate and adaptive cellular and humoral immune responses. Autoantibodies in particular have been shown to be critical in the initiation and progression of renal injury, via interactions with both Fc-receptors and complement. One approach in the management of patients with lupus nephritis has been the use of intravenous immunoglobulin. This therapy has shown benefit in the setting of many forms of autoantibody-mediated injury; however, the mechanisms of efficacy are not fully understood. In this paper, the data supporting the use of immunoglobulin therapy in lupus nephritis will be evaluated. In addition, the potential mechanisms of action will be discussed with respect to the known involvement of complement and Fc-receptors in the kidney parenchyma. Results are provocative and warrant additional clinical trials. PMID:23056926

  17. Immunoglobulins, antibody repertoire and B cell development.

    PubMed

    Butler, J E; Zhao, Y; Sinkora, M; Wertz, N; Kacskovics, I

    2009-03-01

    Swine share with most placental mammals the same five antibody isotypes and same two light chain types. Loci encoding lambda, kappa and Ig heavy chains appear to be organized as they are in other mammals. Swine differ from rodents and primates, but are similar to rabbits in using a single VH family (VH3) to encode their variable heavy chain domain, but not the family used by cattle, another artiodactyl. Distinct from other hoofed mammals and rodents, Ckappa:Clambda usage resembles the 1:1 ratio seen in primates. Since IgG subclasses diversified after speciation, same name subclass homologs do not exist among swine and other mammals unless very closely related. Swine possess six putative IgG subclasses that appear to have diversified by gene duplication and exon shuffle while retaining motifs that can bind to FcgammaRs, FcRn, C1q, protein A and protein G. The epithelial chorial placenta of swine and the precosial nature of their offspring have made piglets excellent models for studies on fetal antibody repertoire development and on the postnatal role of gut colonization, maternal colostrum and neonatal infection on the development of adaptive immunity during the "critical window" of immunological development. This chapter traces the study of the humoral immune system of this species through its various eras of discovery and compiles the results in tables and figures that should be a useful reference for educators and investigators.

  18. Interaction between glycosaminoglycans and immunoglobulin light chains.

    SciTech Connect

    Jiang, X.; Myatt, E.; Lykos, P.; Stevens, F. J.; Center for Mechanistic Biology and Biotechnology; Illinois Inst. of Tech.

    1997-01-01

    Amyloidosis is a pathological process in which normally soluble proteins polymerize to form insoluble fibrils (amyloid). Amyloid formation is found in a number of diseases, including Alzheimer's disease, adult-onset diabetes, and light-chain-associated amyloidosis. No pharmaceutical methods currently exist to prevent this process or to remove the fibrils from tissue. The search for treatment and prevention methods is hampered by a limited understanding of the biophysical basis of amyloid formation. Glycosaminoglycans (GAGs) are long, unbranched heteropolysaccharides composed of repeating disaccharide subunits and are known to associate with amyloid fibrils. The interaction of amyloid-associated free light chains with GAGs was tested by both size-exclusion high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments. The results indicated that heparin 16 000 and chondroitin sulfate B and C precipitated both human intact light chains and recombinant light chain variable domains. Although all light chains interacted with heparin, the strongest interactions were obtained with proteins that had formed amyloid. Molecular modeling indicated the possibility of interaction between heparin and the conserved saddle like surface of the light chain dimer opposite the complementarity-determining segments that form part of the antigen-binding site of a functional antibody. This suggestion might offer a new path to block the aggregation of amyloid-associated light chain proteins, by design of antagonists based on properties of GAG binding. A hexasaccharide was modeled as the basis for a possible antagonist.

  19. Novel region within the V kappa gene promoter is responsible for tissue and stage-specific expression of immunoglobulin genes in human lymphoid neoplasms.

    PubMed

    Kossakowska, A E; Urbanski, S J

    1989-03-01

    Immunoglobulin gene-specific transacting factors have been shown to play a role in lymphoid tissue-specific expression of immunoglobulin genes. The role of these factors in B-cell differentiation and stage-specific expression of these genes is, however, not fully understood. We have used a model of human lymphoid neoplasia to address this question. Different fragments of unrearranged human variable region of immunoglobulin kappa gene (V kappa) were used for cell-free in vitro transcription and DNA mobility shift assays. Previously described enhancement of in vitro transcription that was only seen with nuclear extracts derived from B-cell neoplasms corresponding to the late stages of B-cell differentiation was shown to be dependent on the actions of these factor(s) on the DNA region within the V kappa gene promoter. This region is located within the 920 bp fragment located 210 bp upstream from the coding region and this fragment represents a possible novel DNA region, which plays a role in the stage- and tissue-specific expression of immunoglobulin genes.

  20. Preparation of F(ab')2 fragments of immunoglobulin G.

    PubMed

    Killion, J J; Holtgrewe, E M

    1983-11-01

    We describe a simple protocol for the preparation of F(ab')2 fragments of immunoglobulin G, based upon the known Fc- binding properties of protein A-Sepharose. The fragment preparations of xenogeneic and allogeneic anti-IgG were noncytotoxic to intact target cells, and were able to block the cytotoxicity of intact antibody. This method should therefore be useful for functional studies not requiring biochemical homogeneity.

  1. CD147 Immunoglobulin Superfamily Receptor Function and Role in Pathology

    PubMed Central

    Iacono, Kathryn T.; Brown, Amy L.; Greene, Mark I.; Saouaf, Sandra J.

    2008-01-01

    The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer’s disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced. PMID:17945211

  2. CD147 immunoglobulin superfamily receptor function and role in pathology.

    PubMed

    Iacono, Kathryn T; Brown, Amy L; Greene, Mark I; Saouaf, Sandra J

    2007-12-01

    The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to upregulation of CD147 expression and tumor progression is introduced. PMID:17945211

  3. Ocular manifestations of monoclonal copper-binding immunoglobulin.

    PubMed

    Shah, Sejal; Espana, Edgar M; Margo, Curtis E

    2014-01-01

    The dense accumulation of copper in Descemet membrane and lens capsule is the characteristic manifestation of a circulating monoclonal antibody with strong affinity for copper. The overproduction of this monoclonal immunoglobulin may be associated with either multiple myeloma or a benign monoclonal gammopathy. Despite prolonged exposure to elevated serum copper, no other tissues in the body are adversely affected by this redox metal. We describe the clinical and pathological findings in a 46-year-old woman with this disorder.

  4. Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations*

    PubMed Central

    Fernandes, Daniel Alvarenga; Kido, Ricardo Yoshio Zanetti; Barros, Ricardo Hoelz de Oliveira; Martins, Daniel Lahan; Penachim, Thiago José; Caserta, Nelson Marcio Gomes

    2016-01-01

    We present a case of immunoglobulin G4 (IgG4)-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease. PMID:27141136

  5. Intracellular Neutralization of Virus by Immunoglobulin A Antibodies

    NASA Astrophysics Data System (ADS)

    Mazanec, Mary B.; Kaetzel, Charlotte S.; Lamm, Michael E.; Fletcher, David; Nedrud, John G.

    1992-08-01

    IgA is thought to neutralize viruses at the epithelial surface of mucous membranes by preventing their attachment. Since IgA, a polymeric immunoglobulin, is transported through the lining of epithelial cells by the polymeric-immunoglobulin receptor and since viruses are obligate intracellular parasites, we hypothesized that IgA antibodies may also interfere with viral replication by binding to newly synthesized viral proteins within infected cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the polymeric-immunoglobulin receptor were infected on the apical surface with Sendai virus. Anti-Sendai virus IgA monoclonal antibody delivered from the basolateral surface colocalized with viral protein within the cell, as documented by immunofluorescence. More importantly, anti-viral IgA reduced virus titers >1000-fold (P < 0.0001) in apical supernatants and >10-fold (P < 0.0001) in cell lysates from monolayers treated with anti-viral IgA compared with those treated with either anti-viral IgG or an irrelevant IgA monoclonal antibody. We believe that the differences in viral titers between cell layers treated with specific IgA, which enters the epithelial cell by binding to the polymeric-immunoglobulin receptor, and those treated with specific IgG, which does not enter the cells, or irrelevant IgA indicate that specific intracellular IgA antibodies can inhibit viral replication. Thus, in addition to the classical role of humoral antibodies in extracellular defense, IgA antibody may be able to neutralize microbial pathogens intracellularly, giving IgA a role in host defense that has traditionally been reserved for cell-mediated immunity.

  6. Immunoglobulin determinants on the lymphocytes of normal rabbits

    PubMed Central

    Wolf, B.; Janeway, C. A.; Coombs, R. R. A.; Catty, D.; Gell, P. G. H.; Kelus, A. S.

    1971-01-01

    Experiments have been performed to see if `allelic exclusion' holds with regard to allotypic immunoglobulin determinants on circulating lymphocytes of the rabbit. The b locus allotypes As4 and As6 were investigated and these were measured by the mixed antiglobulin reaction. To investigate whether both allotypic determinants can be expressed on the membrane of any one lymphocyte, a lymphocyte suspension was treated with antibody reagents to both determinants. Adsorption of each antibody was shown by mixed agglutination with indicator red cells carrying either As4 or As6 immunoglobulin; one of the red cell suspensions was labelled with fluorescein isothiocyanate. When lymphocytes of adult heterozygous rabbits were tested, separate As4 and As6 lymphocytes were shown, but often more than 50 per cent of the lymphocytes exhibited both determinants on the same cell. Tests on an artificial mixture of homozygous As44 lymphocytes and homozygous As66 lymphocytes produced only distinct separate rosettes of the two types. Tests were performed on the lymphocytes of baby rabbits resulting from matings of As/46 does × homozygous As/44 bucks. At 2–3 weeks, when maternal As/46 immunoglobulin was present in easily detectable amounts in the sera of all baby rabbits, genetically As/44 animals could be clearly differentiated from genetically As/46 animals; correspondingly in matings with homozygous As/66 bucks. In litters of matings As/44 does × As/66 bucks, As6 determinants could be detected on the lymphocytes before the As6 immunoglobulin could be shown in the serum. In the very young (2–3 weeks) baby heterozygous As/46 rabbits, the majority of lymphocytes reacted as either As4 or As6 with a very much smaller percentage of mixed As46 cells. By the 12th week, the number of cells exhibiting both determinants had increased but not to so high a figure as found in the adults. PMID:4104284

  7. Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y.

    PubMed

    Gilgunn, Sarah; Millán Martín, Silvia; Wormald, Mark R; Zapatero-Rodríguez, Julia; Conroy, Paul J; O'Kennedy, Richard J; Rudd, Pauline M; Saldova, Radka

    2016-01-01

    Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases.

  8. Unusual intracytoplasmic immunoglobulin inclusions in chronic lymphocytic leukaemia.

    PubMed

    Guglielmi, P; Preud'Homme, J L; Gourdin, M F; Reyes, F; Daniel, M T

    1982-01-01

    Unusual intracytoplasmic immunoglobulin inclusions were found by immunofluorescence in three patients with chronic lymphocytic leukaemia. The inclusions contained the same immunoglobulin chains as those detected on the plasma membrane, except for delta chains which were expressed on the cell surface and not in the cytoplasmic inclusions. The cytoplasmic staining persisted throughout culture for 8 or more days. An initial study of patients 1's cells showed that the inclusions contained only mu chains, and kappa chains gradually became apparent after in vitro culture. In a second study, the fresh lymphocytes contained both mu and and kappa chains. Initially, biosynthetic experiments showed production of mu chains which polymerized in the cytoplasm and were not secreted. Subsequently there was synthesis of heavy and light chains which assembled into monomeric subunits that were retained and secretion of free light chains. The apparent molecular weight of these immunoglobulin chains was larger than that of their secretory counterparts. Immunoelectronmicroscopy revealed cytoplasmic mu chains in strands of endoplasmic reticulum. In the two other patients, immunofluorescence displayed unusual staining patterns of bright networks in perinuclear areas. PMID:6275878

  9. Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y

    PubMed Central

    Millán Martín, Silvia; Wormald, Mark R.; Zapatero-Rodríguez, Julia; Conroy, Paul J.; O’Kennedy, Richard J.; Rudd, Pauline M.; Saldova, Radka

    2016-01-01

    Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases. PMID:27459092

  10. Comprehensive N-Glycan Profiling of Avian Immunoglobulin Y.

    PubMed

    Gilgunn, Sarah; Millán Martín, Silvia; Wormald, Mark R; Zapatero-Rodríguez, Julia; Conroy, Paul J; O'Kennedy, Richard J; Rudd, Pauline M; Saldova, Radka

    2016-01-01

    Recent exploitation of the avian immune system has highlighted its suitability for the generation of high-quality, high-affinity antibodies to a wide range of antigens for a number of therapeutic and biotechnological applications. The glycosylation profile of potential immunoglobulin therapeutics is species specific and is heavily influenced by the cell-line/culture conditions used for production. Hence, knowledge of the carbohydrate moieties present on immunoglobulins is essential as certain glycan structures can adversely impact their physicochemical and biological properties. This study describes the detailed N-glycan profile of IgY polyclonal antibodies from the serum of leghorn chickens using a fully quantitative high-throughput N-glycan analysis approach, based on ultra-performance liquid chromatography (UPLC) separation of released glycans. Structural assignments revealed serum IgY to contain complex bi-, tri- and tetra-antennary glycans with or without core fucose and bisects, hybrid and high mannose glycans. High sialic acid content was also observed, with the presence of rare sialic acid structures, likely polysialic acids. It is concluded that IgY is heavily decorated with complex glycans; however, no known non-human or immunogenic glycans were identified. Thus, IgY is a potentially promising candidate for immunoglobulin-based therapies for the treatment of various infectious diseases. PMID:27459092

  11. Organization and expression of immunoglobulin genes in fetal liver hybridomas.

    PubMed

    Perry, R P; Kelley, D E; Coleclough, C; Kearney, J F

    1981-01-01

    The organization and expression of immunoglobulin genes were studied in a series of six hybridomas derived from the fusion of a nonproducing myeloma cell with cells from mouse fetal liver. These hybridomas, which exhibit several phenotypic characteristics of immature B lymphocytes, all have productively rearranged mu heavy chain genes and produce both the membrane and secreted forms of mu mRNA in a ratio of about 1:10. Significantly, none of the hybridomas has an unrearranged (germ line) allelic mu gene. Examination of the kappa light chain genes revealed that all six of the hybridomas contain unrearranged kappa loci and produce 8.4-kilobase transcripts containing kappa constant region sequences. None of the five hybridomas that exhibit a mu-only phenotype contains a rearranged kappa gene other than that derived from the myeloma parent. One hybridoma, which actively secretes kappa immunoglobulin, contains a rearranged kappa gene of fetal liver origin and synthesizes a distinctive kappa mRNA precursor in addition to the 8.4-kilobase transcript. These results demonstrate that rearrangement of heavy chain immunoglobulin genes normally occurs prior to that of light chain genes and further indicate that the transcriptional competence of the kappa constant region locus is established prior to the time of its rearrangement.

  12. Subclasses of immunoglobulins and autoantibodies in autoimmune diseases.

    PubMed

    Outschoorn, I; Rowley, M J; Cook, A D; Mackay, I R

    1993-01-01

    The differing capacity of subclasses of IgG to bind to protein A and protein G was used in a sequential affinity purification procedure to examine immunoglobulin isotypes and subclasses in autoimmune disease. The utility of the procedure is that affinity-purified fractions containing particular isotypes and subclasses of immunoglobulin can be analyzed for their content of autoantibodies using standard techniques. For each of four autoimmune diseases studied, chronic active hepatitis, Sjogren's syndrome, primary biliary cirrhosis, and rheumatoid arthritis, there were characteristic protein elution profiles and the various disease-specific autoantibodies showed preferential distributions among the isotypes and subclasses. Moreover there was not an absolute correlation between an increased level of a particular subclass and the occurrence of antibodies of that subclass. The occurrence of highly disease-specific immunoglobulin subclass profiles suggests that the hypergammaglobulinemia associated with autoimmunity cannot be attributed entirely to polyclonal B-cell activation. Rather, there are disease-specific alterations in isotype subclass switching which may reflect different cytokine-dependent influences on autoimmune B cells and their products.

  13. VH replacement in primary immunoglobulin repertoire diversification.

    PubMed

    Sun, Amy; Novobrantseva, Tatiana I; Coffre, Maryaline; Hewitt, Susannah L; Jensen, Kari; Skok, Jane A; Rajewsky, Klaus; Koralov, Sergei B

    2015-02-01

    The genes encoding the variable (V) region of the B-cell antigen receptor (BCR) are assembled from V, D (diversity), and J (joining) elements through a RAG-mediated recombination process that relies on the recognition of recombination signal sequences (RSSs) flanking the individual elements. Secondary V(D)J rearrangement modifies the original Ig rearrangement if a nonproductive original joint is formed, as a response to inappropriate signaling from a self-reactive BCR, or as part of a stochastic mechanism to further diversify the Ig repertoire. VH replacement represents a RAG-mediated secondary rearrangement in which an upstream VH element recombines with a rearranged VHDHJH joint to generate a new BCR specificity. The rearrangement occurs between the cryptic RSS of the original VH element and the conventional RSS of the invading VH gene, leaving behind a footprint of up to five base pairs (bps) of the original VH gene that is often further obscured by exonuclease activity and N-nucleotide addition. We have previously demonstrated that VH replacement can efficiently rescue the development of B cells that have acquired two nonproductive heavy chain (IgH) rearrangements. Here we describe a novel knock-in mouse model in which the prerearranged IgH locus resembles an endogenously rearranged productive VHDHJH allele. Using this mouse model, we characterized the role of VH replacement in the diversification of the primary Ig repertoire through the modification of productive VHDHJH rearrangements. Our results indicate that VH replacement occurs before Ig light chain rearrangement and thus is not involved in the editing of self-reactive antibodies.

  14. A generic strategy for subcloning antibody variable regions from the scFv phage display vector pCANTAB 5 E into pASK85 permits the economical production of F(ab) fragments and leads to improved recombinant immunoglobulin stability.

    PubMed

    Kramer, Karl; Fiedler, Markus; Skerra, Arne; Hock, Bertold

    2002-04-01

    Apart from the decisive sensitivity and specificity of immunosensors, the employed antibodies essentially contribute to additional key factors like fabrication costs for sensor chips and sensor stability. A production scheme for recombinant antibody fragments has been optimised with respect to these particular issues of biosensor development. The phagemid vector pCANTAB 5 E is widely used for the selection of antibody fragments from corresponding libraries. However, large-scale production of the selected single-chain F(v) (scFv) fragments is substantially restricted by the high cost for the inducer IPTG and the anti-E-tag antibody. The latter is needed in significant amounts for the purification of the recombinant protein. A generic strategy was established for subcloning scFv variable regions from pCANTAB 5 E into the plasmid pASK85 for the expression of F(ab) fragments. pASK85 bears coding sequences for murine constant domains including a His(6) tag at the carboxyl-terminal end of the constant heavy chain domain. The anti-s-triazine antibody K47H served as a model system in this study. Biosynthesis of the F(ab) fragment in a high cell density fermenter was induced by addition of anhydrotetracycline. The F(ab) fragment was subsequently purified from the periplasmic extract in a single step by immobilized metal affinity chromatography (IMAC). A yield of 100 microg/lxOD(550) purified F(ab) fragment was obtained employing a standard fermentation scheme. The sensitivity and cross-reactivity of the F(ab) was comparable to the parent scFv when assayed by enzyme immunoassay. However, the F(ab) fragment exhibited significantly improved long-term stability.

  15. Genetic control of basal serum immunoglobulin E level and its effect on specific reaginic sensitivity.

    PubMed

    Marsh, D G; Bias, W B; Ishizaka, K

    1974-09-01

    Studies of the distribution of total serum immunoglobulin E levels in nonallergic and allergic populations defined a cut-off point between low and high immunoglobulin E at 95 U/ml, based on Mendelian recessive inheritance of high immunoglobulin E level. Subsequent investigations of the distribution of total serum immunoglobulin E levels in 28 allergic families confirmed the recessive hypothesis. The results of quantitative skin tests in eight families, performed with between five and eight highly purified grass and ragweed pollen allergens per family, demonstrate that the immunoglobulin E-regulating gene exerts a profound effect on specific immunoglobulin E-mediated sensitivity, often masking the effect of HL-A associated immune response genes.

  16. Identification of cellular immunoglobulins in chronic lymphocytic leukaemia by immunoperoxidase staining.

    PubMed Central

    Markey, G M; McConnell, R E; Alexander, H D; Morris, T C; Robertson, J H

    1983-01-01

    An indirect immunoperoxidase technique has been used for visualisation of cellular immunoglobulins in chronic lymphocytic leukaemia. Baker's formol calcium was used as fixative. Monoclonal light and heavy chain patterns were demonstrated in 24 out of 27 cases. Only one case did not have any demonstrable immunoglobulins. The presence of alpha or gamma heavy chain immunoglobulin isotypes in leukaemic lymphocytes was found to be related to low mouse rosetting capacity (p less than 0.05). Images PMID:6418770

  17. Anti-RhD immunoglobulin in the treatment of immune thrombocytopenia

    PubMed Central

    Cheung, Eric; Liebman, Howard A

    2009-01-01

    Immune thrombocytopenia (ITP) is an acquired bleeding autoimmune disorder characterized by a markedly decreased blood platelet count. The disorder is variable, frequently having an acute onset of limited duration in children and a more chronic course in adults. A number of therapeutic agents have demonstrated efficacy in increasing the platelet counts in both children and adults. Anti-RhD immunoglobulin (anti-D) is one such agent, and has been successfully used in the setting of both acute and chronic immune thrombocytopenia. In this report we review the use of anti-D in the management of ITP. While the FDA-approved dose of 50 mg/kg has documented efficacy in increasing platelet counts in approximately 80% of children and 70% of adults, a higher dose of 75 μg/kg has been shown to result in a more rapid increase in platelet count without a greater reduction in hemoglobin. Anti-D is generally ineffective in patients who have failed splenectomy. Anti-RhD therapy has been shown capable of delaying splenectomy in adult patients, but does not significantly increase the total number of patients in whom the procedure can be avoided. Anti-D therapy appears to inhibit macrophage phagocytosis by a combination of both FcR blockade and inflammatory cytokine inhibition of platelet phagocytosis within the spleen. Anti-RhD treatment is associated with mild to moderate infusion toxicities. Rare life-threatening toxicities such as hemoglobinuria, acute renal failure and disseminated intravascular coagulation have been reported. Recommendations have been proposed to reduce the risk of these complications. Anti-D immunoglobulin can be an effective option for rapidly increasing platelet counts in patients with symptomatic ITP. PMID:19707396

  18. Phagocytosis of virulent Porphyromonas gingivalis by human polymorphonuclear leukocytes requires specific immunoglobulin G.

    PubMed Central

    Cutler, C W; Kalmar, J R; Arnold, R R

    1991-01-01

    No studies to date clearly define the interactions between Porphyromonas gingivalis and human peripheral blood polymorphonuclear leukocytes (PMN), nor has a protective role for antibody to P. gingivalis been defined. Using a fluorochrome phagocytosis microassay, we investigated PMN phagocytosis and killing of P. gingivalis as a function of P. gingivalis-specific antibody. Sera from a nonimmune rabbit and a healthy human subject were not opsonic for virulent P. gingivalis A7436, W83, and HG405; phagocytosis of these strains (but not 33277) required opsonization with hyperimmune antiserum (RaPg). Diluting RaPg with a constant complement source decreased proportionally the number of P. gingivalis A7436 cells phagocytosed per phagocytic PMN. Enriching for the immunoglobulin G fraction of RAPg A7436 enriched for opsonic activity toward A7436. An opsonic evaluation of 18 serum samples from adult periodontitis patients revealed that only 3 adult periodontitis sera of 17 with elevated immunoglobulin G to P. gingivalis A7436 were opsonic for A7436 and, moreover, that the serum sample with the highest enzyme-linked immunosorbent assay titer was most opsonic (patient 1). However, the opsonic activity of serum from patient 1 was qualitatively and not just quantitatively different from that of the nonopsonic human sera (but was less effective opsonin than RaPg). Strain variability was observed in resistance of P. gingivalis to phagocytosis, and opsonization was strain specific for some, but not all, strains tested. An evaluation of killing of A7436 revealed that serum killing and extracellular killing of P. gingivalis were less effective alone when compared with intracellular PMN killing alone. PMID:2037370

  19. Assessment and Intervention for Young Children with Nonphysiological Feeding Concerns

    ERIC Educational Resources Information Center

    Olive, Melissa

    2004-01-01

    Among families who have young children, feeding concerns are quite common (Brazelton, 1992). Feeding concerns can include, but are not limited to, inappropriate mealtime behaviors, lack of self-feeding, food selectivity, and food refusal (Kerwin, 1999). Given the complex nature of assessment of and intervention for feeding concerns in young…

  20. Improved purification of immunoglobulin G from plasma by mixed-mode chromatography.

    PubMed

    Chai, Dong-Sheng; Sun, Yan; Wang, Xiao-Ning; Shi, Qing-Hong

    2014-12-01

    Efficient loading of immunoglobulin G in mixed-mode chromatography is often a serious bottleneck in the chromatographic purification of immunoglobulin G. In this work, a mixed-mode ligand, 4-(1H-imidazol-1-yl) aniline, was coupled to Sepharose Fast Flow to fabricate AN SepFF adsorbents with ligand densities of 15-64 mmol/L, and the chromatographic performances of these adsorbents were thoroughly investigated to identify a feasible approach to improve immunoglobulin G purification. The results indicate that a critical ligand density exists for immunoglobulin G on the AN SepFF adsorbents. Above the critical ligand density, the adsorbents showed superior selectivity to immunoglobulin G at high salt concentrations, and also exhibited much higher dynamic binding capacities. For immunoglobulin G purification, both the yield and binding capacity increased with adsorbent ligand density along with a decrease in purity. It is difficult to improve the binding capacity, purity, and yield of immunoglobulin G simultaneously in AN SepFF chromatography. By using tandem AN SepFF chromatography, a threefold increase in binding capacity as well as high purity and yield of immunoglobulin G were achieved. Therefore, the tandem chromatography demonstrates that AN SepFF adsorbent is a practical and feasible alternative to MEP HyperCel adsorbents for immunoglobulin G purification.

  1. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues)....

  2. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class...

  3. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class...

  4. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. (b) Classification. Class...

  5. Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2.

    PubMed

    Hirayasu, Kouyuki; Saito, Fumiji; Suenaga, Tadahiro; Shida, Kyoko; Arase, Noriko; Oikawa, Keita; Yamaoka, Toshifumi; Murota, Hiroyuki; Chibana, Hiroji; Nakagawa, Ichiro; Kubori, Tomoko; Nagai, Hiroki; Nakamaru, Yuji; Katayama, Ichiro; Colonna, Marco; Arase, Hisashi

    2016-01-01

    Microbial proteases degrade a variety of host proteins(1-3). However, it has remained largely unknown why microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens. PMID:27572839

  6. Heavy-light chain interrelations of MS-associated immunoglobulins probed by deep sequencing and rational variation.

    PubMed

    Lomakin, Yakov A; Zakharova, Maria Yu; Stepanov, Alexey V; Dronina, Maria A; Smirnov, Ivan V; Bobik, Tatyana V; Pyrkov, Andrey Yu; Tikunova, Nina V; Sharanova, Svetlana N; Boitsov, Vitali M; Vyazmin, Sergey Yu; Kabilov, Marsel R; Tupikin, Alexey E; Krasnov, Alexey N; Bykova, Nadezda A; Medvedeva, Yulia A; Fridman, Marina V; Favorov, Alexander V; Ponomarenko, Natalia A; Dubina, Michael V; Boyko, Alexey N; Vlassov, Valentin V; Belogurov, Alexey A; Gabibov, Alexander G

    2014-12-01

    The mechanisms triggering most of autoimmune diseases are still obscure. Autoreactive B cells play a crucial role in the development of such pathologies and, in particular, production of autoantibodies of different specificities. The combination of deep-sequencing technology with functional studies of antibodies selected from highly representative immunoglobulin combinatorial libraries may provide unique information on specific features in the repertoires of autoreactive B cells. Here, we have analyzed cross-combinations of the variable regions of human immunoglobulins against the myelin basic protein (MBP) previously selected from a multiple sclerosis (MS)-related scFv phage-display library. On the other hand, we have performed deep sequencing of the sublibraries of scFvs against MBP, Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1), and myelin oligodendrocyte glycoprotein (MOG). Bioinformatics analysis of sequencing data and surface plasmon resonance (SPR) studies have shown that it is the variable fragments of antibody heavy chains that mainly determine both the affinity of antibodies to the parent autoantigen and their cross-reactivity. It is suggested that LMP1-cross-reactive anti-myelin autoantibodies contain heavy chains encoded by certain germline gene segments, which may be a hallmark of the EBV-specific B cell subpopulation involved in MS triggering.

  7. Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes

    SciTech Connect

    Grayson, J.; Dooley, N.J.; Koski, I.R.; Blaese, R.M.

    1981-12-01

    The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by (/sup 3/H)thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells.

  8. Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology.

    PubMed

    Yong, Pierre L; Boyle, John; Ballow, Mark; Boyle, Marcia; Berger, Melvin; Bleesing, Jack; Bonilla, Franciso A; Chinen, Javier; Cunninghamm-Rundles, Charlotte; Fuleihan, Ramsay; Nelson, Lois; Wasserman, Richard L; Williams, Kathleen C; Orange, Jordan S

    2010-05-01

    There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined.

  9. Use of intravenous immunoglobulin and adjunctive therapies in the treatment of primary immunodeficiencies: A working group report of and study by the Primary Immunodeficiency Committee of the American Academy of Allergy Asthma and Immunology.

    PubMed

    Yong, Pierre L; Boyle, John; Ballow, Mark; Boyle, Marcia; Berger, Melvin; Bleesing, Jack; Bonilla, Franciso A; Chinen, Javier; Cunninghamm-Rundles, Charlotte; Fuleihan, Ramsay; Nelson, Lois; Wasserman, Richard L; Williams, Kathleen C; Orange, Jordan S

    2010-05-01

    There are an expanding number of primary immunodeficiency diseases (PIDDs), each associated with unique diagnostic and therapeutic complexities. Limited data, however, exist supporting specific therapeutic interventions. Thus, a survey of PIDD management was administered to allergists/immunologists in the United States to identify current perspectives and practices. Among 405 respondents, the majority of key management practices identified were consistent with existing data and guidelines, including the provision of immunoglobulin therapy, immunoglobulin dosing and selective avoidance of live viral vaccines. Practices for which there are little specific data or evidence-based guidance were also examined, including evaluation of IgG trough levels for patients receiving immunoglobulin, use of prophylactic antibiotics and recommendations for complementary/alternative medicine. Here, variability applied to PIDD patients was identified. Differences between practitioners clinically focused upon PIDD and general allergists/immunologists were also identified. Thus, a need for expanded clinical research in PIDD to optimize management and potentially improve outcomes was defined. PMID:19914873

  10. Bovine immunoglobulin protein isolates for the nutritional management of enteropathy.

    PubMed

    Petschow, Bryon W; Blikslager, Anthony T; Weaver, Eric M; Campbell, Joy M; Polo, Javier; Shaw, Audrey L; Burnett, Bruce P; Klein, Gerald L; Rhoads, J Marc

    2014-09-01

    The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.

  11. Killer cell immunoglobulin-like receptor gene association with cryptorchidism.

    PubMed

    Niepiekło-Miniewska, Wanda; Kuśnierczyk, Piotr; Havrylyuk, Anna; Kamieniczna, Marzena; Nakonechnyy, Andrij; Chopyak, Valentyna; Kurpisz, Maciej

    2015-12-01

    Cryptorchidism is a condition where a testis persists in the abdominal cavity. Thus, due to elevated temperature we may expect induction of aberrant immune reactions depending on genetic constitution of individual. This may be reflected by development of anti-sperm antibodies (ASA) in cryptorchid males. Also, natural killer (NK) cells which belong to innate immunity may control adaptive immunity. Therefore, the gene system encoding polymorphic NK cell immunoglobulin receptors (KIRs) has been studied. 109 prepubertal boys with cryptorchidism and 136 ethnically matched young male donors were selected to study NK cell KIRs. DNA was isolated using automatic Maxwell(®) system from the peripheral venous blood drawn onto anticoagulant. Olerup SSP KIR Genotyping kit including Taq polymerase was used for detection of KIR genes. Human leukocyte antigen-C (HLA-C) groups, C1 and C2 were established using a Olerup SSP KIR HLA Ligand kit. KIR2DL2 (killer immunoglobulin-like receptor two-domain long 2) and KIR2DS2 (killer immunoglobulin-like receptor two-domain short 2) genes were less frequent in patients than in control individuals (corrected p values: 0.0110 and 0.0383, respectively). However, no significant differences were observed between ASA-positive and ASA-negative patients, or between bilateral or unilateral cryptorchidism. No association between KIR ligands C1 and C2, alone or together with KIR2DL2, was found. However, the results suggest that KIR2DL2+/KIR2DS2+ genotype may be, to some extent, protective against cryptorchidism.

  12. Bovine immunoglobulin protein isolates for the nutritional management of enteropathy

    PubMed Central

    Petschow, Bryon W; Blikslager, Anthony T; Weaver, Eric M; Campbell, Joy M; Polo, Javier; Shaw, Audrey L; Burnett, Bruce P; Klein, Gerald L; Rhoads, J Marc

    2014-01-01

    The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy. PMID:25206275

  13. Estimation of major immunoglobulins in smokers and gutkha chewers

    PubMed Central

    Prajapati, Ketankumar Jayantilal; Chawda, Jyoti G

    2016-01-01

    Aim: To estimate the level of IgG and IgA major immunoglobulins in patients having the habit of smoking, gutkha chewing and in patients without any tobacco habit as control. Materials and Methods: Estimation of major immunoglobulins IgG and IgA was carried out by automated Nephelometry method in ten patients (control group), forty patients who had habit of smoking either bidi or cigarette and forty patients who had the habit of gutkha chewing. Among forty patients who smoked, twenty patients were without any lesion while twenty patients had homogenous leukoplakia. Among the forty patients who had habit of gutkha chewing, twenty patients were without any lesion while twenty patients had oral submucous fibrosis (OSMF). The obtained data were analyzed using independent sample t-test. Results: IgG and IgA levels were higher in smokers and gutkha chewers as compared to control group and were higher in gutkha chewers as compared to smokers. IgG and IgA levels of non- lesional smokers and gutkha chewers showed no change as compared to the controls while it was increased in patients with homogenous leukoplakia and patients with OSMF as compared to control group. IgG and IgA levels were also significantly higher in patients with OSMF as compared to that of homogenous leukoplakia. IgG and IgA levels were higher in all the grades of OSMF as compared to the controls and both IgG and IgA levels were directly correlated with the grades of OSMF. Conclusion: Higher major immunoglobulins levels in present study among the study groups indicate the use of immunoprofile estimation in etiology and pathogenesis and would prove a great asset in the proper assessment of the lesions. PMID:27601812

  14. Facilitated subcutaneous immunoglobulin (fSCIg) therapy--practical considerations.

    PubMed

    Ponsford, M; Carne, E; Kingdon, C; Joyce, C; Price, C; Williams, C; El-Shanawany, T; Williams, P; Jolles, S

    2015-12-01

    There is an increasing range of therapeutic options for primary antibody-deficient patients who require replacement immunoglobulin. These include intravenous immunoglobulin (IVIg), subcutaneous immunoglobulin (SCIg), rapid push SCIg and most recently recombinant human hyaluronidase-facilitated SCIg (fSCIg). Advantages of fSCIg include fewer needle punctures, longer infusion intervals and an improved adverse effect profile relative to IVIg. Limited real-life experience exists concerning the practical aspects of switching or starting patients on fSCIg. We describe the first 14 patients who have been treated with fSCIg at the Immunodeficiency Centre for Wales (ICW), representing more than 6 patient-years of experience. The regimen was well tolerated, with high levels of satisfaction and no increase in training requirement, including for a treatment-naive patient. Two patients discontinued fSCIg due to pain and swelling at the infusion site, and one paused therapy following post-infusion migraines. Ultrasound imaging of paired conventional and facilitated SCIg demonstrated clear differences in subcutaneous space distribution associated with a 10-fold increase in rate and volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into two main categories: those experiencing clinical problems with their current treatment and those seeking greater convenience and flexibility. When introducing fSCIg, consideration of the type and programming of infusion pump, needle gauge and length, infusion site, up-dosing schedule, home training and patient information are important, as these may differ from conventional SCIg. This paper provides guidance on practical aspects of the administration, training and outcomes to help inform decision-making for this new treatment modality. PMID:26288095

  15. A Case of Immunoglobulin E Mediated Anaphylaxis to Levodropropizine

    PubMed Central

    Park, Kyung Hee; Yun, Il Seon; Choi, Soo-Young; Lee, Jae-Hyun; Hong, Chein-Soo

    2013-01-01

    We experienced a case of immunoglobulin E (IgE) mediated anaphylaxis to levodropropizine. The patient was an 18-year old Korean woman. After taking the common cold medication including acetaminophen, domperidone, and levodropropizine, skin rash, angioedema and anaphylaxis were developed immediately. As she was tolerable to acetaminophen alone, we thought the culprit agent was maybe a levodropropizine tablet. To confirm the culprit, she underwent skin prick test and oral drug provocation test with the suspected one. Finally we detected levodropropizine specific IgE and confirmed the specificity by inhibition enzyme-linked immunosorbent assay (ELISA). PMID:23225830

  16. [Immunoglobulins in the cerebrospinal fluid and blood in acute neuroinfections].

    PubMed

    Dekonenko, E P; Poliakova, T G; Ivanova, L A; Umanskiĭ, K G; Demidova, S A

    1988-01-01

    The authors have examined 42 patients with viral encephalitides and other central nervous system lesions using a complex of clinical and viroimmunological methods of examination. The main emphasis has been laid on measuring immunoglobulins A, M, and G in the blood serum and cerebrospinal fluid. The results have shown marked changes in humoral immunity. The degree of these changes is directly correlated with severity of encephalitis. Investigation into humoral immunity in patients with neuroinfections and other nervous system diseases contributes to the development of differential diagnostic criteria and better understanding of the relationship between severity and outcome of diseases.

  17. Immunoglobulin Concentration in Tears of Contact Lens Wearers

    PubMed Central

    Maurya, Rajendra P.; Bhushan, Prashant; Singh, Virendra P.; Singh, Mahendra K.; Kumar, Prakash; Bhatia, Ravindra P.S.; Singh, Usha

    2014-01-01

    Purpose: To evaluate changes in the concentration of tear immunoglobulins in contact lens wearers. Methods: A total of 45 cases including 23 contact lens wearers (43 eyes) and 22 age and sex matched healthy controls having no ocular pathology were studied for immunoglobulins (IgA, IgG, IgM) in their tears by single radial immunodiffusion method. Results: Most of the cases used soft (56.6%) and semi-soft gas permeable (30.4%) contact lenses. Tear IgM was detected in only 17.4% and tear IgG in 43.6% of contact lens wearers, while in controls IgG was detected in 9.1% but none of the controls had IgM. There was a significant rise in total tear IgA (13.17 ± 4.44 mg/dl) in contact lens wearer as compared to controls (8.93 ± 3.79 mg/dl). Rise of tear IgA was more in symptomatic patients (15.38 ± 5.28 mg/dl) and in those wearing hard (19.73 ± 5.43 mg/dl) and semi-soft contact lenses (13.31 ± 5.43 mg/dl). A significant increase in tear IgA was noticed in subjects wearing lenses for >3 years (15.69 ± 5.39 mg/dl). About 43.4% of lens wearers were symptomatic and 80% of their lenses showed deposits and/or haziness. All cases with IgM in tear were symptomatic. Conclusion: The relation of immunoglobulin concentration with increasing duration of wear and material of contact lens shows that tear immunoglobulin rise accrues due to mechanical stimulation, hence contact lenses should not be used for a long period and lenses of hard nature should be discouraged. The maintenance, cleaning and deproteinization of the lenses are of high importance to avoid immunostimulation. PMID:25667732

  18. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies.

    PubMed

    Tschumper, R C; Dispenzieri, A; Abraham, R S; Henderson, K J; Jelinek, D F

    2013-04-19

    Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.

  19. Human heavy chain disease protein WIS: implications for the organization of immunoglobulin genes.

    PubMed Central

    Franklin, E C; Prelli, F; Frangione, B

    1979-01-01

    Protein WIS is a human gamma3 heavy (H) chain disease immunoglobulin variant whose amino acid sequence is most readily interpreted by postulating that three residues of the amino terminus are followed by a deletion of most of the variable (VH) domain, which ends at the variable-constant (VC) joining region. Then there is a stretch of eight residues, three of which are unusual, while the other five have striking homology to the VC junction sequence. This is followed by a second deletion, which ends at the beginning of the quadruplicated hinge region. These findings are consistent with mutations resulting in deletions of most of the gene coding for the V region and CH1 domain followed by splicing at the VC joining region and at the hinge. These structural features fit well the notion of genetic discontinuity between V and C genes and also suggest similar mechanisms of excision and splicing in the interdomain regions of the C gene of the heavy chain. PMID:106391

  20. Immunoglobulin allotypes and immunoglobulin G subclass responses to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in early-onset periodontitis.

    PubMed Central

    Choi, J I; Ha, M H; Kim, J H; Kim, S J

    1996-01-01

    The present study was performed to estimate the observed frequencies of the immunoglobulin heavy-chain (Gm) and light-chain (Km) allotypes among patients with early-onset periodontitis (EOP) and their effect on the IgG2 subclass responses against Actinobacillus actinomycetemcomitans Y4 and Porphyromonas gingivalis 381, respectively. Sixty-nine EOP patients, including 11 with localized juvenile periodontitis (LJP), 19 who had LJP, 15 with LJP-rapidly progressing periodontitis (RPP), and 24 with RPP, were examined for the Gm and Km allotypes by a hemagglutination inhibition test. Levels of immunoglobulin G2 (IgG2) antibodies against the two organisms were determined by enzyme-linked immunosorbent assay. Fifty race- and age-matched, periodontally healthy subjects were also included as a control group. The observed frequencies of the Gm haplotype afnb and Km(1) were significantly higher in the RPP and LJP groups, respectively. The G2m(n)+ group of those with RPP and the Km(1)+ group of those with LJP had significantly higher levels of IgG2 antibodies to A. actinomycetemcomitans and P. gingivalis, respectively. The results indicate that linkage disequilibrium of the G2m(n) locus in RPP patients or the Km(1) locus in LJP patients may be associated with high IgG2 antibody responses to the respective bacteria. It was reasoned that the IgG2 antibody responses are associated with the immunoglobulin allotypes. The function of IgG2 antibodies in their reaction to different bacterial antigens may be interpreted as either protective or nonprotective in the two different types of EOP (i.e., LJP and RPP). PMID:8926092

  1. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers.

    PubMed

    Martel, Cyril Jean-Marie; Aasted, Bent

    2009-12-15

    Ferret IgG and IgM were purified from normal serum, while ferret IgA was purified from bile. The estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54kDa, 69kDa and 83kDa, respectively. For immunological (ELISA) quantification of ferret immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and mink CD3. Finally, we identified 4 cross-reacting mAbs with specificities against ferret interferon-gamma, TNF-alpha, interleukin-4 and interleukin-8.

  2. The protective role of immunoglobulins in fungal infections and inflammation.

    PubMed

    Elluru, Sri Ramulu; Kaveri, Srini V; Bayry, Jagadeesh

    2015-03-01

    Increased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg.

  3. Immunoglobulin G Expression in Human Sperm and Possible Functional Significance

    PubMed Central

    Yan, Meiling; Zhang, Xiaoyu; Pu, Qinxue; Huang, Tao; Xie, Qingdong; Wang, Yan; Li, Jing; Wang, Yun; Gu, Huan; Huang, Tianhua; Li, Zhiling; Gu, Jiang

    2016-01-01

    Immunoglobulin G (IgG), the major molecule of the immune system, which was traditionally thought to be produced by differentiated B-lymphocytes, had recently been found in non-immune cells including spermatozoa of rabbit testis. To study if human sperms could produce IgG that might play a role in fertilization, we employed immunofluorescent staining, Western blot, in situ hybridization, RT-PCR (reverse transcription polymerase chain reaction) and immunoelectron microscope and found that human sperms were capable of synthesizing IgG. IgG protein and mRNA were detected in the cytoplasm, mainly the neck region of the sperm and IgG immunoreactivity was found to cover the entire sperm cell. The essential enzymes necessary for IgG synthesis and class switching, RAG1 (recombination activating gene 1), RAG2 (recombination activating gene 2) and AID (activation-induced cytidine deaminase), were also detected in the sperm cells. Furthermore, we found that anti-IgG antibody could inhibit sperm from penetrating Zona-free hamster egg with statistical significance. These discoveries suggested that immunoglobulin G could be produced by human sperms and it might play a role during fertilization. PMID:26833114

  4. Serum immunoglobulin levels and humoral immune competence in coalworkers

    SciTech Connect

    Robertson, M.D.; Boyd, J.E.; Collins, H.P.; Davis, J.M.

    1984-01-01

    Serum immunoglobulin (Ig) levels were measured in 788 coalworkers and 121 nonmining controls for comparison with the radiological category of pneumoconiosis after taking into account age and smoking habit. In addition a simple assessment of humoral immune competence was made by estimating the titre of serum antibody against the common gut commensal Escherichia coli. Smoking was found to depress serum IgA and IgM while levels of IgG and IgA increased slightly with age. Men with radiological signs of coalworkers pneumoconiosis (CWP) had significantly raised levels of IgA and IgG with increasing pneumoconiosis category. Even coalworkers with less than category 1 simple pneumoconiosis had raised levels of IgA, suggesting that increased production of this immunoglobulin occurs before radiologically identifiable pathological changes have occurred in the lung tissue. No association between reduced humoral immune competence and radiological category of pneumoconiosis was found. Whether high Ig levels in men exposed to coal dust are merely a passive response to dusted lung tissue or whether they indicate that an immunological process is important in the development of pneumoconiotic lesions remains uncertain.

  5. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

    PubMed Central

    Bever, Katherine M.; Masha, Luke I.; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L.; Sanchorawala, Vaishali; Seldin, David C.; Sloan, J. Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60–11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. PMID:26452981

  6. Update on immunoglobulin A nephropathy, Part I: Pathophysiology

    PubMed Central

    Salvadori, Maurizio; Rosso, Giuseppina

    2015-01-01

    Immunoglobulin A (IgA) nephropathy is one of the most common glomerulonephritis and its frequency is probably underestimated because in most patients the disease has an indolent course and the kidney biopsy is essential for the diagnosis. In the last years its pathogenesis has been better identified even if still now several questions remain to be answered. The genetic wide association studies have allowed to identifying the relevance of genetics and several putative genes have been identified. The genetics has also allowed explaining why some ancestral groups are affected with higher frequency. To date is clear that IgA nephropathy is related to auto antibodies against immunoglobulin A1 (IgA1) with poor O-glycosylation. The role of mucosal infections is confirmed, but which are the pathogens involved and which is the role of Toll-like receptor polymorphism is less clear. Similarly to date whether the disease is due to the circulating immunocomplexes deposition on the mesangium or whether the antigen is already present on the mesangial cell as a “lanthanic” deposition remains to be clarified. Finally also the link between the mesangial and the podocyte injury and the tubulointerstitial scarring, as well as the mechanisms involved need to be better clarified. PMID:26380197

  7. Separation of specific immunoglobulin. 1. Desalination using a membrane system.

    PubMed

    Tishchenko, G; Bleha, M; Skvor, J; Bures, L

    1995-02-01

    Separation of the ammonium sulfate precipitated protein fraction of mouse ascitic fluid, containing the specific immunoglobulin (pI 6.7-6.8; molecular weight 180000), from ammonium sulfate was investigated by means of non-traditional dialysis, based on the difference in diffusion rates of small and large molecules through porous membranes. The experiments were carried out in spiral membrane modules equipped with a Neosepta (AM-2 or ACS-SB) anion exchange membrane and a microfiltration membrane (Synpore or Sartorius). To enhance the driving force for penetration of ammonium sulfate and low-molecular-weight components from solution of ascitic protein fraction into water, a counterpressure was imposed on the side of microfiltration membrane. The flow rate, counterpressure and the pore sizes of microfiltration membranes had a significant effect on the separation process, as expected. The type of the anion exchange membrane had only a small effect. This process makes it possible to desalt the immunoglobulin fraction with high purity and yield in a few hours instead of 5 days.

  8. The immunoglobulin light chain locus of the turkey, Meleagris gallopavo.

    PubMed

    Bao, Yonghua; Wu, Sun; Zang, Yunlong; Wang, Hui; Song, Xiangfeng; Xu, Chunyang; Xie, Bohong; Guo, Yongchen

    2012-06-15

    To date, most jawed vertebrate species encode more than one immunoglobulin light (IgL) chain isotypes. It has been shown that several bird species (chickens, white Pekin or domestic duck, and zebra finches) exclusively express lambda isotype. We analyze here the genomic organization of another bird species turkey IgL genes based on the recently released genome data. The turkey IgL locus located on chromosome 17 spans approximately 75.2kb and contains a single functional V(λ) gene, twenty V(λ) pseudogenes, and a single functional J(λ)-C(λ) block. These data suggest that the genomic organization of bird IgL chain genes seems to be conserved. Ten cDNA clones from turkey Igλ chain containing almost full-length V(λ), J(λ) and C(λ) segments were acquired. The comparison of V(λ) cDNA sequences to all the germline V(λ) segments suggests that turkey species may be generating IgL chain diversity by gene conversion and somatic hypermutation like the chicken. This study provides insights into the immunoglobulin light chain genes in another bird species.

  9. 7th International Immunoglobulin Conference: Interlaken Leadership Awards

    PubMed Central

    Dalakas, M C; Löscher, W N

    2014-01-01

    The Interlaken Leadership Awards (ILAs), established in 2010, are monetary grants pledged annually by CSL Behring to fund research into the use of immunoglobulin (Ig) therapy, especially into its use in neurological disorders. Five recipients of the 2011/2012 Awards were invited to present their research at the 7th International Immunoglobulin Conference. Dr Honnorat reports on paraneoplastic neurological syndromes (PNS). His multi-centre Phase II trial, currently under way, will assess the efficacy of IVIg therapy in treating PNS in the first 3 months of treatment. Dr Geis shows improved disease scores after IVIg treatment in a mouse model of neuromyelitis optica (NMO). It is hoped that these promising results will translate well into human NMO. Dr Schmidt studied IVIg therapy in an mdx mouse model for Duchenne muscular dystrophy (DMD). He reports that motor function improved and myopathic changes in skeletal muscles and creatine kinase release were decreased. Dr Gamez presents the design and rationale for a Phase II clinical trial investigating the preoperative use of IVIg therapy in myasthenia gravis patients to prevent post-operative myasthenic crisis. Dr Goebel reports results from studies elucidating the immune-mediated pathogenesis of complex regional pain syndrome (CRPS), the successful IVIg therapy in a proportion of CRPS patients, and the development of a model for predicting which patients are more likely to respond to Ig therapy. PMID:25546789

  10. 7th International Immunoglobulin Conference: Interlaken Leadership Awards.

    PubMed

    Dalakas, M C; Löscher, W N

    2014-12-01

    The Interlaken Leadership Awards (ILAs), established in 2010, are monetary grants pledged annually by CSL Behring to fund research into the use of immunoglobulin (Ig) therapy, especially into its use in neurological disorders. Five recipients of the 2011/2012 Awards were invited to present their research at the 7th International Immunoglobulin Conference. Dr Honnorat reports on paraneoplastic neurological syndromes (PNS). His multi-centre Phase II trial, currently under way, will assess the efficacy of IVIg therapy in treating PNS in the first 3 months of treatment. Dr Geis shows improved disease scores after IVIg treatment in a mouse model of neuromyelitis optica (NMO). It is hoped that these promising results will translate well into human NMO. Dr Schmidt studied IVIg therapy in an mdx mouse model for Duchenne muscular dystrophy (DMD). He reports that motor function improved and myopathic changes in skeletal muscles and creatine kinase release were decreased. Dr Gamez presents the design and rationale for a Phase II clinical trial investigating the preoperative use of IVIg therapy in myasthenia gravis patients to prevent post-operative myasthenic crisis. Dr Goebel reports results from studies elucidating the immune-mediated pathogenesis of complex regional pain syndrome (CRPS), the successful IVIg therapy in a proportion of CRPS patients, and the development of a model for predicting which patients are more likely to respond to Ig therapy.

  11. [Immunoglobulin genes in lymphoid cells and regulation of their transcription].

    PubMed

    Stepchenko, A G; Urakov, D N; Luchina, N N; Deev, S M; Polianovskiĭ, O L

    1990-01-01

    The hybridoma genomes contain polyploid sets of immunoglobulin genes. We have shown, that the hybridoma PTF-02 genome contains three genes of heavy chains and two genes of light chains. The genes responsible for antibody synthesis were cloned and their structure were determined. Investigation of the kappa gene transcription and its fragments which contain regulatory sequences revealed a nuclear factor. The latter interacts with the octanucleotide localized at the promoter region of the kappa gene. The purified factor activates the transcription of the kappa gene in a heterologous cell-free system. Together with the tissue-specific factor there is also an universal factor interacting with the octanucleotide sequence. We have shown an additional factor in lymphoid cells interact with the protein which binds to the octanucleotide sequence. We have shown an additional factor in lymphoid cells interacting with the protein which binds to the octanucleotide sequence. As a result, there is a family of factors which interact with ATTTGCAT sequence. One major factor (m.w. 60 +/- 2 kDa) is an obligatory component for the initiation of immunoglobulin genes transcription.

  12. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    ERIC Educational Resources Information Center

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

  13. Anti-Clostridium difficile bovine immunoglobulin concentrate inhibits cytotoxicity and enterotoxicity of C. difficile toxins.

    PubMed Central

    Kelly, C P; Pothoulakis, C; Vavva, F; Castagliuolo, I; Bostwick, E F; O'Keane, J C; Keates, S; LaMont, J T

    1996-01-01

    Clostridium difficile diarrhea and colitis result from the actions of bacterial exotoxins on the colonic mucosa. This study examined the ability of hyperimmune bovine colostral antibodies to neutralize the biological effects of these toxins. Anti-C. difficile bovine immunoglobulin concentrate was prepared from the colostral milk of Holstein cows previously immunized with C. difficile toxoids. The anti-C. difficile bovine immunoglobulin concentrate contained high levels of bovine immunoglobulin G specific for C. difficile toxins A and B, as evaluated by enzyme-linked immunosorbent assay. Anti-C. difficile bovine immunoglobulin concentrate neutralized the cytotoxic effects of purified toxin A and toxin B on cultured human fibroblasts, whereas control bovine immunoglobulin concentrate had little toxin-neutralizing activity. Anti-C. difficile bovine immunoglobulin concentrate also blocked the binding of toxin A to its enterocyte receptor and inhibited the enterotoxic effects of C. difficile toxins on the rat ileum, as measured by an increased rat ileal loop weight/length ratio (63% inhibition; P < 0.01), increased mannitol permeability (92% inhibition; P < 0.01), and histologic grading of enteritis (P < 0.01 versus nonimmune bovine immunoglobulin concentrate). Thus, anti-C. difficile bovine immunoglobulin concentrate neutralizes the cytotoxic effects of C. difficile toxins in vitro and inhibits their enterotoxic effects in vivo. This agent may be clinically useful in the prevention and treatment of C. difficile diarrhea and colitis. PMID:8834883

  14. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... resulting from breakdown of immunoglobulin G antibodies in urine, serum, and other body fluids. Measurement... multiple myeloma (tumor of bone marrow cells), Waldenstrom's macroglobulinemia (increased immunoglobulin production by the spleen and bone marrow cells), and lymphoma (tumor of the lymphoid tissues)....

  15. Construction of chimeric antibodies: cloning of immunoglobulin genes including their promoter regions by PCR.

    PubMed

    Mocikat, R; Kütemeier, G; Harloff, C

    1992-03-01

    In the production of recombinant antibodies, it is necessary to have an immunoglobulin gene promoter for driving the expression of the antibody genes. Here we describe a simple PCR method that allows cloning of the immunoglobulin genes together with their own promoters despite the fact that the sequence of the upstream part of the gene is unknown.

  16. Hepatocyte handling of immunoglobulin A in the rat: the role of microtubules

    SciTech Connect

    Goldman, I.S.; Jones, A.L.; Hradek, G.T.; Huling, S.

    1983-07-01

    Plasma-derived dimeric immunoglobulin A is transported through liver parenchymal cells into bile, in association with its glycoprotein receptor secretory component, by a vesicular transport system. This study was designed to determine the effects of colchicine, a microtubule-disrupting agent, and thus the role of microtubules on the uptake, intracellular transport, and subsequent biliary secretion of dimeric immunoglobulin A. In vivo studies in rats showed that colchicine treatment reduced the amount of intraportally injected /sup 125/I-dimeric immunoglobulin A that appeared in the bile. It was also found that although the livers in colchicine-treated animals could sequester and internalize immunoglobulin A, it was not readily secreted into bile. In vitro studies using peroxidase-labeled antisecretory component and /sup 125/I-dimeric immunoglobulin A autoradiography were both used to determine the site of this block in immunoglobulin A secretion. These studies demonstrate that colchicine disruption of microtubules (a) has little initial effect on the binding and internalization of dimeric immunoglobulin A; (b) has a major effect on the translocation of immunoglobulin A-containing vesicles within the hepatocyte, and (c) most likely prevents the translocation of newly synthesized secretory component to the plasma membrane.

  17. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Immunoglobulin (light chain specific) immunological test system. 866.5550 Section 866.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system....

  18. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin (light chain specific) immunological test system. 866.5550 Section 866.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system....

  19. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Immunoglobulin (light chain specific) immunological test system. 866.5550 Section 866.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system....

  20. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Immunoglobulin (light chain specific) immunological test system. 866.5550 Section 866.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system....

  1. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement...

  2. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement...

  3. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement...

  4. 21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Immunoglobulin G (Fd fragment specific) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... fragment) of the heavy chain (a subunit) of the immunoglobulin antibody molecule in serum. Measurement...

  5. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Immunoglobulin (light chain specific) immunological test system. 866.5550 Section 866.5550 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Test Systems § 866.5550 Immunoglobulin (light chain specific) immunological test system....

  6. Common variable immunodeficiency (CVID) presenting with malabsorption due to giardiasis.

    PubMed

    Onbaşi, Kevser; Günşar, Fulya; Sin, Aytül Z; Ardeniz, Omür; Kokuludağ, Ali; Sebik, Filiz

    2005-06-01

    Common variable immunodeficiency is characterized with B-cell and T-cell dysfunction and hypogammaglobulinemia. Recurrent bacterial infections, such as otitis media, chronic sinusitis and recurrent pneumonia due to diminished immunoglobulin (Ig) levels and impaired antibody production are frequently observed in common variable immunodeficiency. Almost half of the patients with common variable immunodeficiency have problems related to the gastrointestinal system. A 39-year-old woman was referred to our department with the complaint of chronic diarrhea. She had experienced diarrhea without mucus or blood in the last year and had lost 30 kg. In her medical history, she had suffered from recurrent upper and lower respiratory infections like sinusitis, otitis media and pneumonia since childhood. Serum immunoglobulin levels were low. There were no parasites or ova in her stool examinations. Esophagogastroduodenoscopy detected widespread macroscopic nodular appearance on duodenum, and biopsies from the duodenum revealed giardiasis invading the tissue. She was diagnosed as common variable immunodeficiency. After metronidazole therapy and intravenous immunoglobulin infusion was started, her diarrhea attacks ceased and she regained her normal weight. Common gastrointestinal system problems in patients with common variable immunodeficiency are lactose intolerance, lymphoid hyperplasia/diffuse lymphoid infiltration, loss of villi and infection, especially with Giardia lamblia. Giardiasis may lead to severe mucosal flattening and sometimes to lymphoid hyperplasia at the lamina propria of the duodenum. Medical history should be evaluated carefully regarding recurrent respiratory infections. In such cases with chronic diarrhea, common variable immunodeficiency should be kept in mind as a possible cause. PMID:16252205

  7. Mucosal immunoglobulins at respiratory surfaces mark an ancient association that predates the emergence of tetrapods.

    PubMed

    Xu, Zhen; Takizawa, Fumio; Parra, David; Gómez, Daniela; von Gersdorff Jørgensen, Louise; LaPatra, Scott E; Sunyer, J Oriol

    2016-01-01

    Gas-exchange structures are critical for acquiring oxygen, but they also represent portals for pathogen entry. Local mucosal immunoglobulin responses against pathogens in specialized respiratory organs have only been described in tetrapods. Since fish gills are considered a mucosal surface, we hypothesized that a dedicated mucosal immunoglobulin response would be generated within its mucosa on microbial exposure. Supporting this hypothesis, here we demonstrate that following pathogen exposure, IgT(+) B cells proliferate and generate pathogen-specific IgT within the gills of fish, thus providing the first example of locally induced immunoglobulin in the mucosa of a cold-blooded species. Moreover, we demonstrate that gill microbiota is predominantly coated with IgT, thus providing previously unappreciated evidence that the microbiota present at a respiratory surface of a vertebrate is recognized by a mucosal immunoglobulin. Our findings indicate that respiratory surfaces and mucosal immunoglobulins are part of an ancient association that predates the emergence of tetrapods. PMID:26869478

  8. Mucosal immunoglobulins at respiratory surfaces mark an ancient association that predates the emergence of tetrapods

    PubMed Central

    Xu, Zhen; Takizawa, Fumio; Parra, David; Gómez, Daniela; von Gersdorff Jørgensen, Louise; LaPatra, Scott E.; Sunyer, J. Oriol

    2016-01-01

    Gas-exchange structures are critical for acquiring oxygen, but they also represent portals for pathogen entry. Local mucosal immunoglobulin responses against pathogens in specialized respiratory organs have only been described in tetrapods. Since fish gills are considered a mucosal surface, we hypothesized that a dedicated mucosal immunoglobulin response would be generated within its mucosa on microbial exposure. Supporting this hypothesis, here we demonstrate that following pathogen exposure, IgT+ B cells proliferate and generate pathogen-specific IgT within the gills of fish, thus providing the first example of locally induced immunoglobulin in the mucosa of a cold-blooded species. Moreover, we demonstrate that gill microbiota is predominantly coated with IgT, thus providing previously unappreciated evidence that the microbiota present at a respiratory surface of a vertebrate is recognized by a mucosal immunoglobulin. Our findings indicate that respiratory surfaces and mucosal immunoglobulins are part of an ancient association that predates the emergence of tetrapods. PMID:26869478

  9. Detection of antirotavirus immunoglobulins A, G, and M in swine colostrum, milk, and feces by enzyme-linked immunosorbent assay.

    PubMed Central

    Corthier, G; Franz, J

    1981-01-01

    An enzyme-linked immunosorbent assay was developed to allow direct detection of class-specific antirotavirus antibodies. In colostrum and in milk, antirotavirus antibodies were found in the three immunoglobulin classes. Antirotavirus immunoglobulins G and M were predominant in colostrum, whereas antirotavirus immunoglobulin A was predominant in milk and feces. PMID:6260678

  10. Myelin-oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex

    SciTech Connect

    Pham-Dinh, D.; Dautigny, A. ); Mattei, M.G.; Roeckel, N. ); Nussbaum, J.H.; Roussel, G. ); Pontarotti, P. ); Mather, I.H. ); Artzt, K. ); Lindahl, K.F. )

    1993-09-01

    Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. The authors have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. The authors colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC. 38 refs., 6 figs.

  11. Molecular analysis of immunoglobulin genes in multiple myeloma.

    PubMed

    Kosmas, C; Stamatopoulos, K; Stavroyianni, N; Belessi, C; Viniou, N; Yataganas, X

    1999-04-01

    The study of immunoglobulin genes in multiple myeloma over the last five years has provided important information regarding biology, ontogenetic location, disease evolution, pathogenic consequences and tumor-specific therapeutic intervention with idiotypic vaccination. Detailed analysis of V(H) genes has revealed clonal relationship between switch variants expressed by the bone marrow plasma cell and myeloma progenitors in the marrow and peripheral blood. V(H) gene usage is biased against V4-34 (encoding antibodies with cold agglutinin specificity; anti-l/i) explaining the absence of autoimmune phenomena in myeloma compared to other B-cell lymphoproliferative disorders. V(H) genes accumulate somatic hypermutations following a distribution compatible with antigen selection, but with no intraclonal heterogeneity. V(L) genes indicate a bias in usage of VkappaI family members and somatic hypermutation, in line with antigen selection, of the expressed Vkappa genes is higher than any other B-cell lymphoid disorder. A complementary imprint of antigen selection as evidenced by somatic hypermutation of either the V(H) or V(L) clonogenic genes has been observed. The absence of ongoing somatic mutations in either V(H) or V(L) genes gives rise to the notion that the cell of origin in myeloma is a post-germinal center memory B-cell. Clinical application of sensitive PCR methods in order to detect clonal immunoglobulin gene rearrangements has made relevant the monitoring and follow-up of minimal residual disease in stem cell autografts and after myeloablative therapy. The fact that surface immunoglobulin V(H) and V(L) sequences constitute unique tumor-specific antigenic determinants has stimulated investigators to devise strategies aiming to generate active specific immunity against the idiotype of malignant B-cells in myeloma by constructing vaccines based on expressed single-chain Fv fragments, DNA plasmids carrying V(H)+V(L) clonogenic genes for naked DNA vaccination, or

  12. Collaborative study for the establishment of the Ph. Eur. BRP batch 1 for anti-vaccinia immunoglobulin.

    PubMed

    Fuchs, F; Poirier, B; Leparc-Goffart, I; Buchheit, K H

    2005-09-01

    Upon suggestion of the French Official Medicines Control Laboratory, a collaborative study was initiated by the European Directorate for the Quality of Medicines with the goal of calibrating the candidate European Pharmacopoeia biological reference preparation (Ph. Eur. BRP) for anti-vaccinia immunoglobulin batch 1 in International Units (IU) against the 1(st) British standard (anti-smallpox serum). The candidate BRP batch 1 was obtained by lyophilising a pool of four plasma samples obtained from one donor who was multi-vaccinated with smallpox vaccine (Lister strain) and who had relatively high titres of neutralising anti-vaccinia antibodies. The plasma complied with the requirements of the Ph. Eur. monograph Human plasma for fractionation. For the candidate BRP the precision of fill and the residual moisture after lyophilisation comply with the requirements for biological reference preparations. The stability of the material was shown to be satisfactory for the intended purpose in an accelerated degradation test. Eight laboratories participated in the study. Two samples had to be assayed (candidate BRP batch 1 and 1(st) British standard). All participants were requested to test the samples using a common method (plaque reduction neutralisation) that had been validated beforehand, and their own in-house anti-vaccinia immunoglobulin titration method. From the raw data returned, the potency of the candidate BRP was calculated in IU/ml using the parallel lines method. The precision (intra-assay variation), repeatability (intra-laboratory variation) and reproducibility (inter-laboratory variation) were assessed. All laboratories used the Lister strain of vaccinia virus for the plaque reduction neutralisation assay. For laboratories using cell-adapted vaccinia virus, the results were satisfactory regarding intra-assay variability, intra-laboratory variability and inter-laboratory variability. For laboratories using vaccinia virus produced on animals, results were less

  13. Management of hypersensitivity reactions to anti-D immunoglobulin preparations.

    PubMed

    Rutkowski, K; Nasser, S M

    2014-11-01

    RhD immunoglobulin G (anti-D) administered to pregnant Rh(-) women prevents Rh isoimmunization. Its use has significantly reduced the incidence of haemolytic disease of the foetus and newborn previously responsible for one death in every 2200 births. In pregnancy, acute drug-induced hypersensitivity reactions including anaphylaxis can have serious deleterious effects on the mother and foetus/neonate. Women can be erroneously labelled as drug allergic as the investigation of hypersensitivity reactions in pregnancy is complex and drug challenges are usually contraindicated. We present three cases of suspected anti-D hypersensitivity clinically presenting as anaphylaxis and delayed transfusion-related reaction. We also propose a new algorithm for the investigations of such reaction. It relies on detailed history, cautious interpretation of skin tests, foetal Rh genotyping from maternal blood and, in some cases, anti-D challenges. This is not to deprive women of anti-D which might put their future pregnancies at risk. PMID:25066207

  14. Pepsinogen--an immunoglobulin binding artefact in 'collagen' preparations.

    PubMed Central

    Kirk, A P; O'Hara, B P; Mageed, R A; McMahon, M S; McCarthy, D; Menashi, S; Archer, J R; Currey, H L

    1986-01-01

    It has previously been shown that extracts of human articular cartilage, many many of which contain type II collagen, react with heat-aggregated immunoglobulin and artificially prepared immune complexes. Sera from patients with rheumatoid arthritis and psoriatic arthritis, but not from patients with inflammatory bowel disease, react with these extracts. There are two distinct patterns of binding, either as low molecular weight immune complexes or as free antibody directed against collagen. Aggregate-binding activity identified in extracts of human articular cartilage following pepsin digestion was found to be distinct from collagen in its salt solubility. Further purification of this aggregate-binding factor by SDS gel electrophoresis has shown it to be an artefact resulting from the binding of small immune complexes to pepsinogen present in the pepsin preparation used to digest the cartilage. Images Fig. 4 PMID:3780048

  15. Intravenous immunoglobulins in peripheral neuropathy associated with vasculitis

    PubMed Central

    Levy, Y; Uziel, Y; Zandman, G; Amital, H; Sherer, Y; Langevitz, P; Goldman, B; Shoenfeld, Y

    2003-01-01

    Objective: To present patients who exhibited various inflammatory diseases accompanied with vasculitic peripheral neuropathies for which intravenous immunoglobulin (IVIg) was used for treatment. Methods: Six patients with Sjögren's syndrome, systemic lupus erythematosus (SLE), vaccination induced vasculitis, Churg-Strauss vasculitis, mixed cryoglobulinaemia associated with hepatitis C infection, or sarcoidosis were included. All developed vasculitic peripheral neuropathy, and were treated with high dose IVIg (2 g/kg body weight). The patients were followed up for 1–5 years after this treatment. Results: In four patients (Sjögren's syndrome, Churg-Strauss vasculitis, SLE, and vaccination induced vasculitis) the neuropathy resolved after IVIg treatment. Conclusion: IVIg may be beneficial in cases of resistant vasculitic peripheral neuropathy. IVIg should probably be considered as a sole or adjuvant treatment for patients with contraindications to conventional treatment, or alternatively, for patients in whom conventional treatment has failed. PMID:14644864

  16. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases.

    PubMed

    Casadevall, Arturo; Pirofski, Liise-Anne

    2012-05-17

    Only two decades ago antibodies to fungi were thought to have little or no role in protection against fungal diseases. However, subsequent research has provided convincing evidence that certain antibodies can modify the course of fungal infection to the benefit or detriment of the host. Hybridoma technology was the breakthrough that enabled the characterization of antibodies to fungi, illuminating some of the requirements for antibody efficacy. As discussed in this review, fungal-specific antibodies mediate protection through direct actions on fungal cells and through classical mechanisms such as phagocytosis and complement activation. Although mechanisms of antibody-mediated protection are often species-specific, numerous fungal antigens can be targeted to generate vaccines and therapeutic immunoglobulins. Furthermore, the study of antibody function against medically important fungi has provided fresh immunological insights into the complexity of humoral immunity that are likely to apply to other pathogens.

  17. Role of immunoglobulin G antibodies in diagnosis of food allergy

    PubMed Central

    Bartuzi, Zbigniew

    2016-01-01

    This paper presents current views on the role of immunoglobulin G (IgG) antibodies in the reactions with food antigens in the digestive tract and their role in the diagnosis of food allergy based on the assays of specific IgG class antibodies, with a special focus on contemporary practice guidelines. In the light of current scientific knowledge, the IgG-specific antibody-mediated reactions are a body's natural and normal defensive reactions to infiltrating food antigens, which are considered as pathogens. On the other hand, specific IgG antibodies against food allergens play a crucial role in the induction and maintaining of immunological tolerance to food antigens. The statements of many scientific societies stress that sIgG are of no significant importance in the diagnosis of food allergy since their presence is associated with a normal immune response to food allergens and attests to a protracted exposure to food antigens.

  18. Intravenous human immunoglobulin for treatment of folliculitis decalvans.

    PubMed

    Ismail, Nuriah; Ralph, Nicola; Murphy, Gillian

    2015-10-01

    We report a case of folliculitis decalvans (FD) successfully treated with intravenous human immunoglobulin (HIG). Many conventional treatments with topical agents and oral antibiotics had failed to achieve disease remission, treatment with HIG at a dose of 2 g/kg for the first month, reduced to 1 g/kg for second to fourth months was therefore started, which resulted in rapid improvement and ultimately complete resolution of FD. Clinical improvement was noted after the first infusion of HIG and remission of inflammation was achieved after the fourth infusion. Disease remission was sustained for six months following the last HIG infusion. The exact mechanism of action of HIG is poorly understood. However, it is thought to act as an immunomodulatory agent by altering different components of immune functions. To our knowledge, this is the first case reported in the literature of FD successfully treated with intravenous HIG.

  19. Immunoglobulin M myeloma: evaluation of molecular features and cytokine expression.

    PubMed

    Konduri, Kartik; Sahota, Surinder S; Babbage, Gavin; Tong, Alex W; Kumar, Padmasini; Newman, Joseph T; Stone, Marvin J

    2005-03-01

    Immunoglobulin (Ig) M myeloma is a distinct entity with features of multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM). The malignant cells in IgM myeloma have a distinctive chromosomal translocation that differentiates them from WM. These cells are postgerminal-center in origin with isotype-switch transcripts. They appear to be arrested at a point of maturation between that of WM and MM. Preliminary data indicate that a pattern of osteoclast-activating factor and osteoprotegerin expression similar to that observed in classic MM is present in IgM myeloma. Additional studies on patients with this rare tumor may provide further insight into the pathogenesis of bone disease in plasma cell dyscrasias.

  20. Anaphylactic shock due to hepatitis B immunoglobulin in a newborn.

    PubMed

    Bulbul, Ali; Karadag, Ahmet; Köklü, Esad; Pamuk, Utku; Sarici, Serdar Umit

    2010-10-01

    Hepatitis B immunoglobulin (HBIG) is administered for the passive immunisation of all infants born to HBsAg-positive mothers within 12 h of birth. Adverse effects of HBIG are very rare. In this study, we report a newborn (a female, 33 weeks' gestation and 2030 g birth weight) developing anaphylaxis after HBIG administration. The mother was a Hepatitis B virus (HBV) carrier. Hypotension and erythematous rash developed 7 min after HBIG administration. Reporting the first anaphylaxis case in newborns due to HBIG in literature, we suggest the condition be taken into account, and requisite precautions should be taken against this probable complication in the newborn. PMID:20210693

  1. Intravenous immunoglobulin in neurological disease: a specialist review

    PubMed Central

    Wiles, C; Brown, P; Chapel, H; Guerrini, R; Hughes, R; Martin, T; McCrone, P; Newsom-Davis, J; Palace, J; Rees, J; Rose, M; Scolding, N; Webster, A

    2002-01-01

    Treatment of neurological disorders with intravenous immunoglobulin (IVIg) is an increasing feature of our practice for an expanding range of indications. For some there is evidence of benefit from randomised controlled trials, whereas for others evidence is anecdotal. The relative rarity of some of the disorders means that good randomised control trials will be difficult to deliver. Meanwhile, the treatment is costly and pressure to "do something" in often distressing disorders considerable. This review follows a 1 day meeting of the authors in November 2000 and examines current evidence for the use of IVIg in neurological conditions and comments on mechanisms of action, delivery, safety and tolerability, and health economic issues. Evidence of efficacy has been classified into levels for healthcare interventions (tables 1 and 2). PMID:11909900

  2. Characterization of a lymphoblastoid line deleted for lambda immunoglobulin genes

    SciTech Connect

    Hough, C.A., White, B.N., Holden, J.A.

    1995-04-01

    While characterizing the cat eye syndrome (CES) supernumerary chromosome for the presence of {lambda} immunoglobulin gene region sequences, a lymphoblastoid cell line from one CES patient was identified in which there was selection of cells deleted from some IGLC and IGLV genes. Two distinct deletions, one on each chromosome 22, were identified, presumably arising from independent somatic recombination events occurring during B-lymphocyte differentiation. The extent of the deleted regions was determined using probes from the various IGLV subgroups and they each covered at least 82 kilobases. The precise definition of the deletions was not possible because of conservation of some restriction sites in the IGLV region. The cell line was used to map putative IGLV genes within the recombinant phage {lambda}V{lambda}135 to the distal part of the IGLV gene region. 35 refs., 4 figs.

  3. Chronic myopathy due to immunoglobulin light chain amyloidosis

    PubMed Central

    Manoli, Irini; Kwan, Justin Y.; Wang, Qian; Rushing, Elisabeth J.; Tsokos, Maria; Arai, Andrew E.; Burch, Warner M.; Dispenzieri, Angela; McPherron, Alexandra C.; Gahl, William A.

    2013-01-01

    Amyloid myopathy associated with a plasma cell dyscrasia is a rare cause of muscle hypertrophy. It can be a challenging diagnosis, since pathological findings are often elusive. In addition, the mechanism by which immunoglobulin light-chain deposition stimulates muscle overgrowth remains poorly understood. We present a 53–year old female with a 10-year history of progressive generalized muscle overgrowth. Congo-red staining and immunohistochemistry revealed perivascular lambda light chain amyloid deposits, apparent only in a second muscle biopsy. The numbers of central nuclei and satellite cells were increased, suggesting enhanced muscle progenitor cell formation. Despite the chronicity of the light chain disease, the patient showed complete resolution of hematologic findings and significant improvement of her muscle symptoms following autologous bone marrow transplantation. This case highlights the importance of early diagnosis and therapy for this treatable cause of a chronic myopathy with muscle hypertrophy. PMID:23465863

  4. Intravenous immunoglobulin treatment in a patient with adrenomyeloneuropathy

    PubMed Central

    2012-01-01

    Background Adrenomyeloneuropathy (AMN) is one of several phenotypes of the adrenoleukodystrophy spectrum caused by mutations in the ABCD1 gene on the X chromosome. An inflammatory component is part of the disease complex ranging from severe childhood CNS demyelination to spinal cord and peripheral nerve degeneration. Case presentation We present a patient with clinical progressive AMN and severe lower limb pain. Longitudinal brain magnetic resonance spectroscopy showed a constant slightly elevated myoinositol/total creatine ratio during the five year treatment period, probably reflecting demyelination, microglial activation and gliosis, indicating an inflammatory response. The pain was refractory to conventional therapy but intravenous immunoglobulin (IVIG) treatment was highly efficient. Conclusion IVIG may be considered as a last resort for treatment of refractory pain in AMN patients with indications of an inflammatory component. PMID:23009600

  5. Role of immunoglobulin G antibodies in diagnosis of food allergy

    PubMed Central

    Bartuzi, Zbigniew

    2016-01-01

    This paper presents current views on the role of immunoglobulin G (IgG) antibodies in the reactions with food antigens in the digestive tract and their role in the diagnosis of food allergy based on the assays of specific IgG class antibodies, with a special focus on contemporary practice guidelines. In the light of current scientific knowledge, the IgG-specific antibody-mediated reactions are a body's natural and normal defensive reactions to infiltrating food antigens, which are considered as pathogens. On the other hand, specific IgG antibodies against food allergens play a crucial role in the induction and maintaining of immunological tolerance to food antigens. The statements of many scientific societies stress that sIgG are of no significant importance in the diagnosis of food allergy since their presence is associated with a normal immune response to food allergens and attests to a protracted exposure to food antigens. PMID:27605894

  6. Role of immunoglobulin G antibodies in diagnosis of food allergy.

    PubMed

    Gocki, Jacek; Bartuzi, Zbigniew

    2016-08-01

    This paper presents current views on the role of immunoglobulin G (IgG) antibodies in the reactions with food antigens in the digestive tract and their role in the diagnosis of food allergy based on the assays of specific IgG class antibodies, with a special focus on contemporary practice guidelines. In the light of current scientific knowledge, the IgG-specific antibody-mediated reactions are a body's natural and normal defensive reactions to infiltrating food antigens, which are considered as pathogens. On the other hand, specific IgG antibodies against food allergens play a crucial role in the induction and maintaining of immunological tolerance to food antigens. The statements of many scientific societies stress that sIgG are of no significant importance in the diagnosis of food allergy since their presence is associated with a normal immune response to food allergens and attests to a protracted exposure to food antigens. PMID:27605894

  7. Primary immunoglobulin repertoire development: time and space matter.

    PubMed

    Granato, Alessandra; Chen, Yuezhou; Wesemann, Duane R

    2015-04-01

    The primary immunoglobulin repertoire develops via opposing forces of expanding diversification balanced by contracting selection mechanisms. The resulting shape is essential for host health and immune fitness. While the molecular mechanisms of Ig diversification have largely been defined, selection forces shaping emerging Ig repertoires are poorly understood. During lifetime, human and mouse early B cell development occurs at distinct locations-beginning in fetal liver before transferring to bone marrow and spleen by the end of gestation. During an early life window of time, the murine gut lamina propria harbors developing immature B cells in proximity to intestinal contents such as commensal microbes and dietary antigens. Location and timing of early B cell development may thus endow neighboring antigens with primary repertoire-shaping capabilities.

  8. Childhood Pemphigus Foliaceus with Exclusive Immunoglobulin G Autoantibodies to Desmocollins.

    PubMed

    Geller, Shamir; Gat, Andrea; Harel, Avikam; Mashiah, Jacob; Zeeli, Tal; Eming, Rüdiger; Ishii, Norito; Hertl, Michael; Hashimoto, Takashi; Sprecher, Eli

    2016-01-01

    Pemphigus refers to a group of potentially fatal blistering skin diseases that are often due to the deleterious effects of autoantibodies directed against desmosomal antigens. Although desmogleins have been mainly implicated as autoantigens in pemphigus, a steadily growing body of evidence suggests that other desmosomal proteins may be causally involved as well. Antibodies directed against desmocollin-3 have been shown to play a direct role in the pathogenesis of several types of pemphigus. Here we describe the case of a child with localized pemphigus foliaceus and immunoglobulin G (IgG) reactivity exclusively directed to desmocollins. The present report suggests that autoantibodies against nondesmoglein antigens may play a role in the pathogenesis of superficial pemphigus, in addition to pemphigus vulgaris, paraneoplastic pemphigus, and IgA pemphigus. PMID:26758100

  9. Impedimetric immunoglobulin G immunosensor based on chemically modified graphenes

    NASA Astrophysics Data System (ADS)

    Loo, Adeline Huiling; Bonanni, Alessandra; Ambrosi, Adriano; Poh, Hwee Ling; Pumera, Martin

    2012-01-01

    Immunosensors which display high sensitivity and selectivity are of utmost importance to the biomedical field. Graphene is a material which has immense potential for the fabrication of immunosensors. For the first time, we evaluate the immunosensing capabilities of various graphene surfaces in this work. We propose a simple and label-free electrochemical impedimetric immunosensor for immunoglobulin G (IgG) based on chemically modified graphene (CMG) surfaces such as graphite oxide, graphene oxide, thermally reduced graphene oxide and electrochemically reduced graphene oxide. Disposable electrochemical printed electrodes were first modified with CMG materials before anti-immunoglobulin G (anti-IgG), which is specific to IgG, was immobilized. The principle of detection lies in the changes in impedance spectra of the redox probe after the attachment of IgG to the immobilized anti-IgG. It was found that thermally reduced graphene oxide has the best performance when compared to the other CMG materials. In addition, the optimal concentration of anti-IgG to be deposited onto the modified electrode surface is 10 μg ml-1 and the linear range of detection of the immunosensor is from 0.3 μg ml-1 to 7 μg ml-1. Finally, the fabricated immunosensor also displays selectivity for IgG.Immunosensors which display high sensitivity and selectivity are of utmost importance to the biomedical field. Graphene is a material which has immense potential for the fabrication of immunosensors. For the first time, we evaluate the immunosensing capabilities of various graphene surfaces in this work. We propose a simple and label-free electrochemical impedimetric immunosensor for immunoglobulin G (IgG) based on chemically modified graphene (CMG) surfaces such as graphite oxide, graphene oxide, thermally reduced graphene oxide and electrochemically reduced graphene oxide. Disposable electrochemical printed electrodes were first modified with CMG materials before anti-immunoglobulin G (anti

  10. 7th International Immunoglobulin Conference: Interlaken Leadership Awards

    PubMed Central

    Dalakas, M C; Löscher, W N

    2014-01-01

    The research presented in this section explores novel applications of immunoglobulin (Ig) therapy in neurological disorders. The results from the upcoming and ongoing trials of Drs Honnorat and Gamez are expected to provide meaningful insights into the treatment of two serious and disabling diseases. The results already being reported from the work of Drs Schmidt and Geis in animal models seem promising, but further proof-of-concept research is warranted to translate their significance to human diseases. Dr Goebel's work in developing animal models of complex regional pain syndrome (CRPS) may provide new insights into predicting which CRPS patients could respond to Ig therapy or other immunotherapies. The work being made possible by a number of the Interlaken Leadership Awards may provide fundamental insights in understanding neurological disorders and improving quality of life for the patients who suffer from them. PMID:25546795

  11. 7th International Immunoglobulin Conference: Interlaken Leadership Awards.

    PubMed

    Dalakas, M C; Löscher, W N

    2014-12-01

    The research presented in this section explores novel applications of immunoglobulin (Ig) therapy in neurological disorders. The results from the upcoming and ongoing trials of Drs Honnorat and Gamez are expected to provide meaningful insights into the treatment of two serious and disabling diseases. The results already being reported from the work of Drs Schmidt and Geis in animal models seem promising, but further proof-of-concept research is warranted to translate their significance to human diseases. Dr Goebel's work in developing animal models of complex regional pain syndrome (CRPS) may provide new insights into predicting which CRPS patients could respond to Ig therapy or other immunotherapies. The work being made possible by a number of the Interlaken Leadership Awards may provide fundamental insights in understanding neurological disorders and improving quality of life for the patients who suffer from them.

  12. Allelic exclusion of immunoglobulin genes: models and mechanisms.

    PubMed

    Vettermann, Christian; Schlissel, Mark S

    2010-09-01

    The allelic exclusion of immunoglobulin (Ig) genes is one of the most evolutionarily conserved features of the adaptive immune system and underlies the monospecificity of B cells. While much has been learned about how Ig allelic exclusion is established during B-cell development, the relevance of monospecificity to B-cell function remains enigmatic. Here, we review the theoretical models that have been proposed to explain the establishment of Ig allelic exclusion and focus on the molecular mechanisms utilized by developing B cells to ensure the monoallelic expression of Ig kappa and Ig lambda light chain genes. We also discuss the physiological consequences of Ig allelic exclusion and speculate on the importance of monospecificity of B cells for immune recognition.

  13. Not only immunoglobulins, C-reactive protein too.

    PubMed

    Agrawal, Alok

    2013-12-01

    The purpose of this letter is to expand a discussion, published recently in Molecular Immunology, on the post-secretion gain of function by immunoglobulins. It was reported that some circulating IgG molecules in all healthy individuals acquire novel antigen-binding specificity after exposure to conditions that change protein conformation, such as acidic pH. Another protein, C-reactive protein, also acquires novel ligand-binding specificity post-secretion after a switch from its native pentameric conformation to non-native pentameric conformation. Thus, that the functions of a protein depend upon its alternate structural states, and therefore on the surrounding milieu, is a more general phenomenon for some ancient molecules of the immune system than previously thought.

  14. Immunoglobulin A in Bovine Milk: A Potential Functional Food?

    PubMed

    Cakebread, Julie A; Humphrey, Rex; Hodgkinson, Alison J

    2015-08-26

    Immunoglobulin A (IgA) is an anti-inflammatory antibody that plays a critical role in mucosal immunity. It is found in large quantities in human milk, but there are lower amounts in bovine milk. In humans, IgA plays a significant role in providing protection from environmental pathogens at mucosal surfaces and is a key component for the establishment and maintenance of intestinal homeostasis via innate and adaptive immune mechanisms. To date, many of the dairy-based functional foods are derived from bovine colostrum, targeting the benefits of IgG. IgA has a higher pathogenic binding capacity and greater stability against proteolytic degradation when ingested compared with IgG. This provides IgA-based products greater potential in the functional food market that has yet to be realized.

  15. Functional Properties of Human Cytomegalovirus Hyperimmunoglobulin and Standard Immunoglobulin Preparations.

    PubMed

    Germer, Matthias; Herbener, Peter; Schüttrumpf, Jörg

    2016-09-06

    BACKGROUND Cytomegalovirus hyperimmunoglobulin (CMV-HIG) preparations reduce mortality after solid organ transplantation. Polyspecific intravenous immunoglobulin (IVIg) products are also used prophylactically by some centers. Since direct comparative characterizations of the preparations are scarce, it is challenging to compare different clinical studies. MATERIAL AND METHODS The functionality of 2 CMV-HIG preparations (Cytotect® CP, Cytogam®) and 2 IVIg preparations (Ig Vena®, Flebogamma®) were compared in terms of: (i) CMV-specific immunoglobulin G (IgG) antibody levels determined by enzyme-linked immunoabsorbent assay (ELISA), (ii) avidity index using a CMV IgG avidity enzyme immunoassay, (iii) immunoblot assay against CMV-specific antigens, and (iv) anti-CMV microneutralization assay. RESULTS Median CMV-specific IgG antibody concentration was similar in the 2 CMV-HIG preparations (Cytotect® CP 101.8 PEIU/ml, Cytogam® 112.5 PEIU/ml) but markedly lower in the IVIg preparations (13.5 PEIU/ml and 21.3 PEIU/ml). CMV binding avidity was virtually identical for both CMV-HIG products (~90%). Immunoblot assay showed consistently high binding of both CMV-HIG preparations against all antigenic CMV glycoproteins tested. Recognition of some CMV-specific antigens (IE1, CM2, and p65) was weaker for the 2 IVIg products. Median CMV neutralizing antibody titers were identical for both CMV-HIG preparations (1:256), and 4-fold lower (1:64) for the IVIg products. CMV IgG antibody concentration correlated with the CMV neutralization titer. CONCLUSIONS Compared to the polyspecific IVIg products tested here, CMV-HIG preparations showed higher CMV binding activity and wider recognition of tested CMV-specific glycoprotein antigens, with markedly higher neutralizing activity. There do not appear to be any relevant distinctions between the Cytotect® CP and Cytogam® CMV-HIG products in terms of functional activity.

  16. Expression of immunoglobulin kappa and lambda chains in mink.

    PubMed

    Bovkun, L A; Peremislov, V V; Nayakshin, A M; Belousov, E S; Mechetina, L V; Aasted, B; Taranin, A V

    1993-08-01

    The ratio of kappa and lambda chains of immunoglobulins varies significantly from one species to another. It has previously been thought that lambda was only type expressed in mink. We tested mink immunoglobulin light chains using two monoclonal antibodies G80 and G88. It has been shown that G80 and G88 specifically recognize two antigenically different subpopulations of the light chains. Immunochemical analysis of these subpopulations separated by affinity chromatography suggested that they represent lambda and kappa types of light chains, respectively. Screening of a mink cDNA library with monoclonal antibody G88 resulted in the isolation of clone pIGK-1 containing kappa chain-encoding sequence. The cDNA insert of pIGK-1 included most of the V segment, as well as the J, C and 3' untranslated sequences. Mink V kappa sequence shown the highest homology with the human V kappa II subgroup genes (76-79%). Mink C kappa sequence was 53-63% homologous to C kappa of other species. The striking feature of mink C kappa chain is the presence of glutamine in the C-terminal position. Southern blot analysis suggested that mink haploid genome has one C kappa gene and multiple V kappa genes. The kappa:lambda chain ratio in the 12 minks studied was, on the average, 46:54. The same ratio was observed for the kappa- and lambda-producing cells in the mesenteric lymph nodes. The five previously identified mink light chain allotypes were assigned to the lambda chains, thereby confirming that lambda chains in this species are additionally subdivided into several subtypes.

  17. Functional Properties of Human Cytomegalovirus Hyperimmunoglobulin and Standard Immunoglobulin Preparations.

    PubMed

    Germer, Matthias; Herbener, Peter; Schüttrumpf, Jörg

    2016-01-01

    BACKGROUND Cytomegalovirus hyperimmunoglobulin (CMV-HIG) preparations reduce mortality after solid organ transplantation. Polyspecific intravenous immunoglobulin (IVIg) products are also used prophylactically by some centers. Since direct comparative characterizations of the preparations are scarce, it is challenging to compare different clinical studies. MATERIAL AND METHODS The functionality of 2 CMV-HIG preparations (Cytotect® CP, Cytogam®) and 2 IVIg preparations (Ig Vena®, Flebogamma®) were compared in terms of: (i) CMV-specific immunoglobulin G (IgG) antibody levels determined by enzyme-linked immunoabsorbent assay (ELISA), (ii) avidity index using a CMV IgG avidity enzyme immunoassay, (iii) immunoblot assay against CMV-specific antigens, and (iv) anti-CMV microneutralization assay. RESULTS Median CMV-specific IgG antibody concentration was similar in the 2 CMV-HIG preparations (Cytotect® CP 101.8 PEIU/ml, Cytogam® 112.5 PEIU/ml) but markedly lower in the IVIg preparations (13.5 PEIU/ml and 21.3 PEIU/ml). CMV binding avidity was virtually identical for both CMV-HIG products (~90%). Immunoblot assay showed consistently high binding of both CMV-HIG preparations against all antigenic CMV glycoproteins tested. Recognition of some CMV-specific antigens (IE1, CM2, and p65) was weaker for the 2 IVIg products. Median CMV neutralizing antibody titers were identical for both CMV-HIG preparations (1:256), and 4-fold lower (1:64) for the IVIg products. CMV IgG antibody concentration correlated with the CMV neutralization titer. CONCLUSIONS Compared to the polyspecific IVIg products tested here, CMV-HIG preparations showed higher CMV binding activity and wider recognition of tested CMV-specific glycoprotein antigens, with markedly higher neutralizing activity. There do not appear to be any relevant distinctions between the Cytotect® CP and Cytogam® CMV-HIG products in terms of functional activity. PMID:27595792

  18. AID-targeting and hypermutation of non-immunoglobulin genes does not correlate with proximity to immunoglobulin genes in germinal center B cells.

    PubMed

    Gramlich, Hillary Selle; Reisbig, Tara; Schatz, David G

    2012-01-01

    Upon activation, B cells divide, form a germinal center, and express the activation induced deaminase (AID), an enzyme that triggers somatic hypermutation of the variable regions of immunoglobulin (Ig) loci. Recent evidence indicates that at least 25% of expressed genes in germinal center B cells are mutated or deaminated by AID. One of the most deaminated genes, c-Myc, frequently appears as a translocation partner with the Ig heavy chain gene (Igh) in mouse plasmacytomas and human Burkitt's lymphomas. This indicates that the two genes or their double-strand break ends come into close proximity at a biologically relevant frequency. However, the proximity of c-Myc and Igh has never been measured in germinal center B cells, where many such translocations are thought to occur. We hypothesized that in germinal center B cells, not only is c-Myc near Igh, but other mutating non-Ig genes are deaminated by AID because they are near Ig genes, the primary targets of AID. We tested this "collateral damage" model using 3D-fluorescence in situ hybridization (3D-FISH) to measure the distance from non-Ig genes to Ig genes in germinal center B cells. We also made mice transgenic for human MYC and measured expression and mutation of the transgenes. We found that there is no correlation between proximity to Ig genes and levels of AID targeting or gene mutation, and that c-Myc was not closer to Igh than were other non-Ig genes. In addition, the human MYC transgenes did not accumulate mutations and were not deaminated by AID. We conclude that proximity to Ig loci is unlikely to be a major determinant of AID targeting or mutation of non-Ig genes, and that the MYC transgenes are either missing important regulatory elements that allow mutation or are unable to mutate because their new nuclear position is not conducive to AID deamination.

  19. ANTIBODY AND IMMUNOGLOBULIN PRODUCTION AT THE CELLULAR LEVEL IN BURSECTOMIZED-IRRADIATED CHICKENS

    PubMed Central

    Alm, Gunnar V.; Peterson, Raymond D. A.

    1969-01-01

    The effect of bursectomy combined with sublethal X-irradiation in the newly hatched chicken on the immunoglobulin and antibody producing capacity in later life was investigated. The previous findings of a significant incidence of hypogammaglobulinemia in such animals were confirmed. Spleen cells from severely hypogammaglobulinemic animals synthesized and secreted little or no immunoglobulin. Such spleen lymphoid cells contained fewer immunoglobulin antigenic determinants than spleen cells from irradiated control animals as evidenced by their relative inability to respond by an increased DNA synthesis after in vitro culture with rabbit antiserum to chicken immunoglobulin. Therefore, the deficiency in the immunoglobulin synthesis extends not only to actively secreting cells such as plasma cells, but to the entire lymphoid cell population. As expected, most irradiated-bursectomized chickens, irrespective of plasma immunoglobulin levels failed to produce detectable amount of circulating antibodies to Brucella abortus antigen in the primary immune response. Severely hypogammaglobulinemic animals were completely unable to elaborate any plaque forming cells (PFC) in the primary response to sheep red blood cells (SRBC). The results of this investigation support the contention that in the severely hypogammaglobulinemic bursectomized-irradiated chicken the entire antibody producing and immunoglobulin producing cell line is absent. The possibility remains that precursor or stem cells are present but are not appropriately directed to antibody synthesis by other cell types. PMID:4181832

  20. Inhibitory potential of Buffalo (Bubalus bubalis) colostrum immunoglobulin G on Klebsiella pneumoniae.

    PubMed

    L S, Mamatha Bhanu; Nishimura, S-I; H S, Aparna

    2016-07-01

    The unique components of colostrum like free oligosaccharides and glycoconjugates are known to offer resistance to enzymatic digestion in the gastrointestinal tract and have the ability to inhibit the localized adherence of enteropathogens to the digestive tract of the neonates. In this context, we have evaluated the in vitro effect of buffalo colostrum immunoglobulin G on human pathogen Klebsiella pneumoniae, a predominant multidrug resistant pathogen associated with nasocomial infections. The investigation revealed growth inhibitory potential of immunoglobulin G in a dose dependent manner supported by scanning electron microscopic studies. The N-glycan enriched fraction of immunoglobulin G after PNGase treatment was found more effective, comparable to ampicillin than native immunoglobulin G supporting the fact that colostrum derived oligosaccharides is crucial and act as ideal substrates for undesirable and pathogenic bacteria. The MALDI TOF/TOF analysis confirmed the glycostructures of abundant N-glycans of immunoglobulin G exerting antibacterial activity. The proteomic analysis revealed variations between control and treated cells and expression of chemotaxis-CheY protein (14kDa) was evidenced in response to immunoglobulin G treatment. Hence, it would be interesting to investigate the mode of inhibition of multidrug-resistant K. pneumoniae by buffalo colostrum immunoglobulin G with the identification of a newly expressed signalling protein.

  1. The ubiquitous octamer-binding protein(s) is sufficient for transcription of immunoglobulin genes.

    PubMed

    Johnson, D G; Carayannopoulos, L; Capra, J D; Tucker, P W; Hanke, J H

    1990-03-01

    All immunoglobulin genes contain a conserved octanucleotide promoter element, ATGCAAAT, which has been shown to be required for their normal B-cell-specific transcription. Proteins that bind this octamer have been purified, and cDNAs encoding octamer-binding proteins have been cloned. Some of these proteins (referred to as OTF-2) are lymphoid specific, whereas at least one other, and possibly more (referred to as OTF-1), is found ubiquitously in all cell types. The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear. We have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro. Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene. Furthermore, OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity. These results suggest that OTF-1, without OTF-2, is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression.

  2. High-quality full-length immunoglobulin profiling with unique molecular barcoding.

    PubMed

    Turchaninova, M A; Davydov, A; Britanova, O V; Shugay, M; Bikos, V; Egorov, E S; Kirgizova, V I; Merzlyak, E M; Staroverov, D B; Bolotin, D A; Mamedov, I Z; Izraelson, M; Logacheva, M D; Kladova, O; Plevova, K; Pospisilova, S; Chudakov, D M

    2016-09-01

    High-throughput sequencing analysis of hypermutating immunoglobulin (IG) repertoires remains a challenging task. Here we present a robust protocol for the full-length profiling of human and mouse IG repertoires. This protocol uses unique molecular identifiers (UMIs) introduced in the course of cDNA synthesis to control bottlenecks and to eliminate PCR and sequencing errors. Using asymmetric 400+100-nt paired-end Illumina sequencing and UMI-based assembly with the new version of the MIGEC software, the protocol allows up to 750-nt lengths to be sequenced in an almost error-free manner. This sequencing approach should also be applicable to various tasks beyond immune repertoire studies. In IG profiling, the achieved length of high-quality sequence covers the variable region of even the longest chains, along with the fragment of a constant region carrying information on the antibody isotype. The whole protocol, including preparation of cells and libraries, sequencing and data analysis, takes 5 to 6 d. PMID:27490633

  3. Affinity purification of egg yolk immunoglobulins (IgY) using a human mycoplasma protein.

    PubMed

    Jiang, Xuemei; Diraviyam, Thirumalai; Zhang, Xiaoying

    2016-02-15

    Egg yolk immunoglobulin (IgY) is a superior functional equivalent to mammalian IgG. However, the preparation of refined and highly purified IgY is still attributed as difficult task. Protein M (a transmembrane protein from human mycoplasma) has been newly demonstrated as an ideal affinity regent for mammalian antibody purification. This study aimed to evaluate the interaction between protein M and IgY. The results showed protein M could be a superior affinity reagent for IgY, scFv as well as IgYΔFc, based on pull down and western blot investigations; in addition, it was found that ∼125 times increase of effective IgY in the elutent was obtained using protein M affinity chromatography column compared with traditional IgY extraction methods. This indicates, the purification strategy of protein M is entirely different to traditional IBPs and the salient purification feature of protein M would be a breakthrough for purifying not only non-mammalian antibodies, but also monoclonal antibodies and engineered antibodies based on variable region.

  4. Specific immobilization of human immunoglobulin G on gold-coated silicon microcantilever array

    NASA Astrophysics Data System (ADS)

    Vashist, Sandeep Kumar; Tewari, Rupinder; Bajpai, Ram Prakash; Bharadwaj, Lalit Mohan; Raiteri, Roberto

    2007-01-01

    We demonstrate a procedure for immobilizing human immunoglobulin G (IgG) on an array of gold-coated silicon microcantilevers. The procedure employed protein A for the specific immobilization of human IgG on the gold surface. Protein A bound specifically to the gold-coated upper surface of the silicon microcantilever and had no interaction with the silicon surface. It binds to the constant F c regions of human IgG keeping the antigen binding sites on the variable F ab region free to bind to antigens. Fluorescent microscopy was done to analyze qualitatively the biomolecular binding of human IgG using FITC labeled goat anti-human IgG. The immobilization densities of protein A and human IgG were 112+/-19 ng/cm2 and 629+/-23ng/cm2, as determined employing horse radish peroxidase (HRP) labeled biomolecules by 3, 3', 4, 4'-tetramethyl benzidine (TMB) substrate assay. The uniformness of the biomolecular coatings was further determined by atomic force microscopy (AFM). Surface plasmon resonance (SPR) was used to cross-validate the immobilization density of functional human IgG molecules immobilized on the gold surface w.r.t. that obtained by TMB substrate assay.

  5. Binding of mouse immunoglobulin G to polylysine-coated glass substrate for immunodiagnosis

    NASA Astrophysics Data System (ADS)

    Vashist, Sandeep Kumar; Tewari, Rupinder; Bajpai, Ram Prakash; Bharadwaj, Lalit Mohan; Raiteri, Roberto

    2006-12-01

    We report a method for immobilizing mouse immunoglobulin G (IgG) on polylysine-coated glass substrate for immunodiagnostic applications. Mouse IgG molecules were immobilized on polylysine-coated glass substrate employing 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and protein A. The amino groups of the polylysine-coated glass slide were cross linked to the carboxyl groups of protein A employing EDC crosslinker. Protein A was employed as it binds to the constant Fc region of antibodies keeping their antigen binding sites on the variable F ab region free to bind to antigens. The qualitative analysis of surface immobilized mouse IgG was done by fluorescent microscopy employing fluorescein isothiocyanate (FITC) labeled mouse IgG molecules. The immobilization densities of protein A and mouse IgG were determined by 3, 3', 4, 4'-tetramethyl benzidine (TMB) substrate assay employing horse radish peroxidise labelled molecules and were found to be 130 +/- 17 ng/cm2 and 596 +/- 31 ng/cm2 respectively. The biomolecular coatings analyzed by atomic force microscopy (AFM) were found to be uniform.

  6. Predicting the Response to Intravenous Immunoglobulins in an Animal Model of Chronic Neuritis

    PubMed Central

    Pfaff, Johannes; Mathys, Christian; Mausberg, Anne K.; Bendszus, Martin; Pham, Mirko; Hartung, Hans-Peter; Kieseier, Bernd C.

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non-responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker. PMID:27711247

  7. Academic stress differentially influences perceived stress, salivary cortisol, and immunoglobulin-A in undergraduate students.

    PubMed

    Murphy, Lara; Denis, Randy; Ward, Christopher P; Tartar, Jaime L

    2010-07-01

    Academic examination stress is reported to increase physiological and self-report measures of stress and to decrease immune functioning. Here, we investigate biochemical and self-report measures of stress, immune functioning, and academic pressures before and during a midterm examination period. Undergraduate students were asked to complete a measure of global stress, the perceived stress scale (PSS-10), and to indicate their current level of perceived stress. They also answered questions regarding specific academic pressures and provided a saliva sample for cortisol and salivary immunoglobulin-A (S-IgA) quantification. Students showed increased salivary cortisol concentrations and also reported greater acute perceived stress during the examination period compared to the non-examination period. Although cortisol concentrations and perceived stress were significantly higher during the examination period, participants reported similar levels of global stress (PSS-10) during both testing sessions. Additional analyses showed a non-significant increase in the level of S-IgA from the non-examination period to the examination period. Specific pressure variables that appeared to contribute to stress regulation during the examination week included the amount of time spent studying and concern about the impact of examinations in the future. By demonstrating measures of chronic examination stress, these findings provide new insight into the complex relationship between examination stress, cortisol, and immune functioning.

  8. Intravenous immunoglobulin in neurology--mode of action and clinical efficacy.

    PubMed

    Lünemann, Jan D; Nimmerjahn, Falk; Dalakas, Marinos C

    2015-02-01

    Intravenous immunoglobulin (IVIg)-a preparation of polyclonal serum IgG pooled from thousands of blood donors-has been used for nearly three decades, and is proving to be an efficient anti-inflammatory and immunomodulatory treatment for a growing number of neurological diseases. Evidence from controlled clinical trials has established IVIg as a first-line therapy for Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. IVIg is also an effective rescue therapy in some patients with worsening myasthenia gravis, and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. IVIg has been tested in some neurodegenerative disorders, but a controlled study in Alzheimer disease yielded disappointing results. Despite its widespread use and therapeutic success, the mechanisms of action of IVIg are poorly understood. Several hypotheses, based on the function of either the variable or constant IgG fragments, have been proposed to explain IVIg's immunomodulatory activity. This Review highlights emerging data on the mechanisms of action of IVIg related to its anti-inflammatory activity, especially that involving the cellular Fcγ receptors and Fc glycosylation. We also summarize recent trials in neurological diseases, discuss potential biomarkers of efficacy, offer practical guidelines on administration, and provide a rationale for experimental trials in neuroinflammatory disorders.

  9. Mathematical analysis of antigen selection in somatically mutated immunoglobulin genes associated with autoimmunity.

    PubMed

    MacDonald, C M; Boursier, L; D'Cruz, D P; Dunn-Walters, D K; Spencer, J

    2010-09-01

    Affinity maturation is a process by which low-affinity antibodies are transformed into highly specific antibodies in germinal centres. This process occurs by hypermutation of immunoglobulin heavy chain variable (IgH V) region genes followed by selection for high-affinity variants. It has been proposed that statistical tests can identify affinity maturation and antigen selection by analysing the frequency of replacement and silent mutations in the complementarity determining regions (CDRs) that contact antigen and the framework regions (FRs) that encode structural integrity. In this study three different methods that have been proposed for detecting selection: the binomial test, the multinomial test and the focused binomial test, have been assessed for their reliability and ability to detect selection in human IgH V genes. We observe first that no statistical test is able to identify selection in the CDR antigen-binding sites, second that tests can reliably detect selection in the FR and third that antibodies from nasal biopsies from patients with Wegener's granulomatosis and pathogenic antibodies from systemic lupus erythematosus do not appear to be as stringently selected for structural integrity as other groups of functional sequences.

  10. The Application of Magnetic Bead Selection to Investigate Interactions between the Oral Microbiota and Salivary Immunoglobulins

    PubMed Central

    Madhwani, Tejal

    2016-01-01

    The effect of humoral immunity on the composition of the oral microbiota is less intensively investigated than hygiene and diet, in part due to a lack of simple and robust systems for investigating interactions between salivary immunoglobulins and oral bacteria. Here we report the application of an ex situ method to investigate the specificity of salivary immunoglobulins for salivary bacteria. Saliva collected from six volunteers was separated into immunoglobulin and microbial fractions, and the microbial fractions were then directly exposed to salivary immunoglobulins of “self” and “non-self” origin. Antibody-selected bacteria were separated from their congeners using a magnetic bead system, selective for IgA or IgG isotypes. The positively selected fractions were then characterized using gel-based eubacterial-specific DNA profiling. The eubacterial profiles of positively selected fractions diverged significantly from profiles of whole salivary consortia based on volunteer (P≤ 0.001%) and immunoglobulin origin (P≤ 0.001%), but not immunoglobulin isotype (P = 0.2). DNA profiles of separated microbial fractions were significantly (p≤ 0.05) less diverse than whole salivary consortia and included oral and environmental bacteria. Consortia selected using self immunoglobulins were generally less diverse than those selected with immunoglobulins of non-self origin. Magnetic bead separation facilitated the testing of interactions between salivary antibodies and oral bacteria, showing that these interactions are specific and may reflect differences in recognition by self and non-self immunoglobulins. Further development of this system could improve understanding of the relationship between the oral microbiota and the host immune system and of mechanisms underlying the compositional stability of the oral microbiota. PMID:27483159

  11. The Application of Magnetic Bead Selection to Investigate Interactions between the Oral Microbiota and Salivary Immunoglobulins.

    PubMed

    Madhwani, Tejal; McBain, Andrew J

    2016-01-01

    The effect of humoral immunity on the composition of the oral microbiota is less intensively investigated than hygiene and diet, in part due to a lack of simple and robust systems for investigating interactions between salivary immunoglobulins and oral bacteria. Here we report the application of an ex situ method to investigate the specificity of salivary immunoglobulins for salivary bacteria. Saliva collected from six volunteers was separated into immunoglobulin and microbial fractions, and the microbial fractions were then directly exposed to salivary immunoglobulins of "self" and "non-self" origin. Antibody-selected bacteria were separated from their congeners using a magnetic bead system, selective for IgA or IgG isotypes. The positively selected fractions were then characterized using gel-based eubacterial-specific DNA profiling. The eubacterial profiles of positively selected fractions diverged significantly from profiles of whole salivary consortia based on volunteer (P≤ 0.001%) and immunoglobulin origin (P≤ 0.001%), but not immunoglobulin isotype (P = 0.2). DNA profiles of separated microbial fractions were significantly (p≤ 0.05) less diverse than whole salivary consortia and included oral and environmental bacteria. Consortia selected using self immunoglobulins were generally less diverse than those selected with immunoglobulins of non-self origin. Magnetic bead separation facilitated the testing of interactions between salivary antibodies and oral bacteria, showing that these interactions are specific and may reflect differences in recognition by self and non-self immunoglobulins. Further development of this system could improve understanding of the relationship between the oral microbiota and the host immune system and of mechanisms underlying the compositional stability of the oral microbiota. PMID:27483159

  12. Comparison of anti-D immunoglobulin, methylprednisolone, or intravenous immunoglobulin therapy in newly diagnosed pediatric immune thrombocytopenic purpura.

    PubMed

    Celik, Muhittin; Bulbul, Ali; Aydogan, Gönül; Tugcu, Deniz; Can, Emrah; Uslu, Sinan; Dursun, Mesut

    2013-02-01

    This study aimed to evaluate the efficacy, cost, and effects of anti-D immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin (IVIG) therapy on the development of chronic disease in children who are Rh-positive with diagnosed immune thrombocytopenic purpura (ITP). Children with newly diagnosed ITP and platelet count <20,000/mm(3) were prospectively randomized to treatment with anti-D Ig (50 μg/kg), methylprednisolone (2 mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7 years were divided into three equal groups. No difference was observed between platelet counts before treatment and on day 3 of treatment. However, platelet counts at day 7 were lower in the methylprednisolone group than in the IVIG group (P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were significantly lower at the end of treatment (P < 0.05). Chronic ITP developed in 30% of the anti-D Ig group, 35% of the methylprednisolone group, and 25% of the IVIG group, but no significant difference was noted among the groups. The cost analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig and 10.9 times higher than methylprednisolone. In the treatment of ITP in childhood, one 50 μg/kg dose of anti-D Ig has similar effects to IVIG and methylprednisolone. Among patients who were treated with anti-D Ig, serious anemia was not observed, and the cost of treatment was less than that of IVIG treatment.

  13. Non-immune binding of human protein Fv to immunoglobulins from various mammalian and non-mammalian species.

    PubMed

    Bouvet, J P; Pires, R; Charlemagne, J; Pillot, J; Iscaki, S

    1991-10-01

    Reactivity of the secretory protein Fv with immunoglobulins (Ig) from various species of vertebrates was investigated. Binding was observed throughout all taxonomic classes: mammalian, avian, reptilian, amphibian and fish. Contrasting with this wide spectrum, no significant binding was found with most mammalian ungulates, such as horse (Perissodactyl), cow, sheep and goat (Artiodactyls). Nevertheless, disruption of the hydrogen bonds of Ig allowed these non-reactive molecules to bind. Such a conserved reactivity during evolution, and our previous data on the effect of the cleavage of the intra-chain disulphide bonds, suggest that protein Fv recognizes a discontinuous framework structure involving both the FR1 and FR3 regions in the variable domain of the heavy chain of Ig. PMID:1925412

  14. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

    PubMed Central

    Townsend, Catherine L.; Laffy, Julie M. J.; Wu, Yu-Chang Bryan; Silva O’Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K.

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response. PMID:27729912

  15. Pathophysiology of B-cell intrinsic immunoglobulin class switch recombination deficiencies.

    PubMed

    Durandy, Anne; Taubenheim, Nadine; Peron, Sophie; Fischer, Alain

    2007-01-01

    B-cell intrinsic immunoglobulin class switch recombination (Ig-CSR) deficiencies, previously termed hyper-IgM syndromes, are genetically determined conditions characterized by normal or elevated serum IgM levels and an absence or very low levels of IgG, IgA, and IgE. As a function of the molecular mechanism, the defective CSR is variably associated to a defect in the generation of somatic hypermutations (SHMs) in the Ig variable region. The study of Ig-CSR deficiencies contributed to a better delineation of the mechanisms underlying CSR and SHM, the major events of antigen-triggered antibody maturation. Four Ig-CSR deficiency phenotypes have been so far reported: the description of the activation-induced cytidine deaminase (AID) deficiency (Ig-CSR deficiency 1), caused by recessive mutations of AICDA gene, characterized by a defect in CSR and SHM, clearly established the role of AID in the induction of the Ig gene rearrangements underlying CSR and SHM. A CSR-specific function of AID has, however, been detected by the observation of a selective CSR defect caused by mutations affecting the C-terminus of AID. Ig-CSR deficiency 2 is the consequence of uracil-N-glycosylase (UNG) deficiency. Because UNG, a molecule of the base excision repair machinery, removes uracils from DNA and AID deaminates cytosines into uracils, that observation indicates that the AID-UNG pathway directly targets DNA of switch regions from the Ig heavy-chain locus to induce the CSR process. Ig-CSR deficiencies 3 and 4 are characterized by a selective CSR defect resulting from blocks at distinct steps of CSR. A further understanding of the CSR machinery is expected from their molecular definition. PMID:17560278

  16. Rare problems with RhD immunoglobulin for postnatal prophylaxis after large fetomaternal haemorrhage.

    PubMed

    Biscoe, Amber; Kidson-Gerber, Giselle

    2015-12-01

    We report a case of unusually large fetomaternal haemorrhage in a RhD- patient; of symptomatic non-sustained haemolysis of fetal red cells in the maternal circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a failure to prevent RhD alloimmunisation. The haemolytic reaction is not previously reported in this patient group and we suggest would be limited to patients where the number of fetal red cells in the circulation is high. We advocate caution in treatment and spaced dosing of RhD immunoglobulin where the required dose is high, and refer readers to the WinRhoSDF™ RhD immunoglobulin product information for their updated dosing recommendations. There is a need for better understanding of pathophysiology and RhD immunoglobulin effects, to further reduce alloimmunisation rates, and we support the reporting of prophylaxis failures to haemovigilance programmes as is in place in the United Kingdom. PMID:27512480

  17. Elevated vitreous concentration of monoclonal immunoglobulin manifesting as schlieren in juvenile rheumatoid arthritis-associated uveitis.

    PubMed

    Nguyen, Q D; Humphrey, R L; Dunn, J P; Humayun, M S

    2001-02-01

    We report the clinical findings and analysis of the immunoglobulin (Ig) composition of the vitreous of a 10-year-old girl with juvenile rheumatoid arthritis-associated uveitis. The vitreous had a schlieren appearance at the time of pars plana lensectomy and vitrectomy. Analysis of the vitreous fluid revealed marked elevation of IgG, IgM, IgA, and albumin levels relative to vitreous fluids from control patients without uveitis. The immunoglobulin coefficients were also elevated for the IgG and IgM classes of immunoglobulins. Immunofixation electrophoresis of the vitreous fluid revealed 2 distinct bands of restricted electrophoretic mobility. These studies suggest that there may be local (intraocular) production of immunoglobulins as an immunologic response in ocular inflammatory diseases such as juvenile rheumatoid arthritis-associated uveitis and that this immunologic response may be monoclonal (possibly biclonal or oligoclonal) in nature.

  18. Assay of immunoglobulins in supernatants of lymphoid cell lines by conventional laser nephelometry.

    PubMed

    Virella, G; Muñoz, J; Robinson, J E; Goust, J M

    1979-03-01

    An adaptation of the nephelometric assay for serum immunoglobulins has been developed for detection and quantitation of extracellular immunoglobulins in cultures of lymphoblastoid cell lines. This assay employs the standard equipment for laser nephelometry and commercial reagents for immunoglobulin quantitation. By adjusting dilutions of controls and sample volumes of culture supernatants, amounts of IgG and IgM below 1 microgram/ml can be detected in culture supernatants. At concentrations between 1 and 4 microgram/ml, day-to-day and within-run variations for IgM assays were 16 and 11% respectively. The possibility of measuring immunoglobulins secreted by cell lines by conventional laser nephelometry opens several areas of application in the study of the functional activity of B cells and of cell-cell interactions. PMID:313634

  19. [Intravenous immunoglobulin therapy in Morvan syndrome secondary to recurrent thymic carcinoma].

    PubMed

    Horta Baas, Gabriel

    2015-11-25

    Morvan's syndrome is a rare autoimmune channelopathy. A case of Morvan's syndrome is presented as a paraneoplastic syndrome associated to the recurrence of a well-differentiated thymic carcinoma, which showed a good clinical response to treatment with intravenous immunoglobulin.

  20. The ultrastructural localization of immunoglobulins in human b cells of immunoproliferative diseases.

    PubMed

    Gourdin, M F; Farcet, J P; Reyes, F

    1982-06-01

    The cellular distribution of immunoglobulins in human malignant and normal B cells was investigated by immunoelectron microscopy by direct incubation of fixed cells with electron microscopy by direct incubation of fixed cells with peroxidase-coupled antibody. These conjugates penetrated into the cell, resulting in the simultaneous detection of surface and cytoplasmic immunoglobulins. The latter were seen as specific intracisternal staining of the perinuclear space and endoplasmic reticulum and occasionally of the Golgi complex. Plasma cells were frequently characterized by a heterogeneity of reactivity of the endoplasmic reticulum. Minute amounts of cytoplasmic immunoglobulin were demonstrated in cells without developed secretory organelles, such as lymphoma cells and lymphocytes from chronic lymphocytic leukemia (CLL). The method allowed us to define several subsets of cells according to the expression of surface and cytoplasmic immunoglobulins and thus to determine the stage of maturation of cells involved in monoclonal proliferation. PMID:7044445

  1. Immunoperoxidase staining of surface and intracellular immunoglobulin in human neoplastic lymphoid cells.

    PubMed

    Mason, D Y; Leonard, R C; Laurent, G; Gourdin, M F

    1980-07-01

    An immunoperoxidase technique for the optical microscopic detection of cellular immunoglobulin has been used to stain fixed smears of human neoplastic B lymphoid cells. Only four out of 28 cases of chronic lymphatic leukaemia (CLL) showed membrane labelling by this technique. In contrast, when 14 samples from other types of B lymphoproliferative disorder (including hairy cell leukaemia, non-Hodgkin's lymphoma, and prolymphocytic leukaemia) were studied, all samples showed membrane immunoglobulin labelling (confirmed by capping experiments). This discrepancy was attributed to the greater density of surface immunoglobulin present on neoplastic cells in the latter group of disorders compared to CLL. This immunoperoxidase technique is therefore less sensitive than immunofluorescent staining of cells in suspension for the demonstration of neoplastic cell surface immunoglobulin. However, it offers a number of advantages (eg, excellent visualisation of cell morphology, permanence of stained preparations, and applicability to stored samples) which recommend it as the method of choice in certain clinical haematological contexts. PMID:7000833

  2. Serum immunoglobulin E and hyaluronate levels in children living along major roads

    SciTech Connect

    Shima, Masayuki; Adachi, Motoaki

    1996-11-01

    To assess the effects of automobile exhaust on human health, we determined serum concentrations of total immunoglobulin E and hyaluronate in 185 schoolchildren who lived in a district that contained major roads. Serum immunoglobulin E levels were elevated in children who had asthma or wheezing, but levels did no t differ with respect to distance of their homes from the major roads. Serum hyaluronate levels were higher in children who lived less than 50 m from the roadside, compared with children who resided a greater distance from roads. The difference, however, was significant only in a subgroup of children in whom immunoglobulin E levels exceeded 250 IU/ml. Our results suggest that serum hyaluronate levels in children reflect the effects of traffic-related air pollution. Children with high immunoglobulin E levels appeared to be particularly susceptible to the effects of automobile exhaust. 34 refs., 2 figs., 3 tabs.

  3. Interaction between immunoglobulin allotypes and NK receptor genes in diabetes post-hepatitis C virus infection.

    PubMed

    Granados-Montiel, Julio; Zúñiga, Joaquin; Azocar, Jose; Feris, Edmond J; Terreros, Daniel; Larsen, Charles E; Clavijo, Olga P; Cruz-Lagunas, Alfredo; Middleton, Derek; Alper, Chester A; Pandey, Janardan P; Yunis, Edmond J

    2011-06-01

    Genetic interactions between natural killer (NK) cells immunoglobulin-like receptor (KIR) genes and immunoglobulin allotypes have been previously reported in type 2 diabetes mellitus (DM) patients. Puerto Rican Americans with a history of intravenous drug use who developed DM following HCV infection (n=32) were compared to individuals infected with HCV without diabetes (n=121) and to DM non-infected individuals (n=95). Subjects were genotyped for KIRs and immunoglobulin allotypes. We found interactions of immunoglobulin allotypes KM3/KM3 with NK inhibitory receptors 2DL3/2DL3, 2DL1 in the absence of 2DS4 associated with susceptibility to DM in HCV infected individuals. These data suggest the possibility that a subset of patients with HCV could have an immune-mediated component contributing to the development of DM.

  4. Ectopic recombination within homologous immunoglobulin mu gene constant regions in a mouse hybridoma cell line.

    PubMed Central

    Baker, M D; Read, L R

    1992-01-01

    We have transferred a pSV2neo vector containing the wild-type constant region of the immunoglobulin mu gene (C mu) into the mutant hybridoma igm482, which bears a 2-bp deletion in the third constant-region exon of its haploid chromosomal mu gene (C mu 3). Independent igm482 transformants contain the wild-type immunoglobulin C mu region stably integrated in ectopic chromosomal positions. We report here that the wild-type immunoglobulin C mu region can function as the donor sequence in a gene conversion event which corrects the 2-bp deletion in the mutant igm482 chromosomal C mu 3 exon. The homologous recombination event restores normal immunoglobulin M production in the mutant cell. Images PMID:1406631

  5. Self-administered hyaluronidase-facilitated subcutaneous immunoglobulin therapy in complicated primary antibody deficiencies.

    PubMed

    Danieli, Maria Giovanna; Pulvirenti, Federica; Rocchi, Valeria; Morariu, Ramona; Quinti, Isabella

    2016-09-01

    Hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIg) is a new immunoglobulin product for replacement therapy in patients with primary antibody deficiencies (PAD). The pre-administration of recombinant human hyaluronidase associated with 10% immunoglobulin allowed the infusion of larger (up to 600 ml) amounts of immunoglobulin at a single infusion site, enabling patients to receive the necessary treatment in a single monthly dose. Here, we report the effectiveness and the tolerability of fSCIg in patients with severe PAD-related comorbidities: refractory autoimmune thrombocytopenia; systemic granulomatous disease; severe enteropathy, and Type I diabetes. We conclude that fSCIg could be a feasible option to improve the adherence to replacement therapy also by patients with severe PAD. PMID:27485073

  6. Surface bound or cytoplasmic immunoglobulins: interpretation of the immunofluorescence observed in cytocentrifuge slides of human lymphocytes.

    PubMed Central

    Schuit, H R; Hijmans, W; Jansen, J

    1984-01-01

    Results of immunofluorescence observations in the study of normal and malignant blood lymphocytes are described. Data which support the proposition that most membrane bound immunoglobulin molecules are stable enough to remain intact during cytocentrifuge slide preparation are presented. Therefore not all positive cells in a fixed cytocentrifuge slide should be considered as containing cytoplasmic immunoglobulins. A correct interpretation is essential because of its bearing on our concepts of B lymphocyte differentiation. Images Fig. 3 PMID:6378456

  7. Effects of intravenous immunoglobulins on T-cell mediated, concanavalin A-induced hepatitis in mice.

    PubMed

    Shirin, H; Bruck, R; Aeed, H; Hershkoviz, R; Lider, O; Kenet, G; Avni, Y; Halpern, Z

    1997-12-01

    Concanavalin A (ConA) activates T lymphocytes and causes T-cell mediated hepatic injury in mice. The intravenous administration of human immunoglobulins has beneficial effects in T-cell mediated diseases such as experimental autoimmune encephalomyelitis and adjuvant arthritis. In the present study, we examined the effects of intravenous immunoglobulins in a mouse model of T-cell mediated, acute liver injury induced by concanavalin A. Balb/c mice were inoculated with 12 mg/kg concanavalin A with or without intravenous immunoglobulins at doses of 0.4, 0.6, 0.8 g/kg body wt. The serum levels of liver enzymes, tumor necrosis factor-alpha, interferon-gamma and interleukin-6 were assayed 2, 6 and 24 h after concanavalin A administration. Intravenous immunoglobulins did not prevent concanavalin A-induced hepatitis, as manifested by elevation of serum aminotransferases and histopathological evaluation. The serum levels of tumor necrosis factor-alpha in mice pretreated with immunoglobulins, measured 2 h after ConA treatment were reduced, while interferon-gamma levels measured 6 h after ConA inoculation were 5-fold higher than control levels. There was no effect of intravenous immunoglobulins on the release of interleukin 6. In conclusion, these results indicate that intravenous immunoglobulin is not effective in preventing T-cell mediated concanavalin A-induced hepatitis. The increased secretion of interferon-gamma and the incomplete suppression of tumor necrosis factor-alpha release may explain the lack of efficacy of intravenous immunoglobulin in this experimental model. PMID:9455732

  8. Introduction of human gamma 1 immunoglobulin genes into fertilized mouse eggs.

    PubMed

    Yamamura, K; Kikutani, H; Takahashi, N; Taga, T; Akira, S; Kawai, K; Fukuchi, K; Kumahara, Y; Honjo, T; Kishimoto, T

    1984-08-01

    A rearranged human gamma 1 immunoglobulin gene was introduced into fertilized mouse eggs. The phage Ch4A-VCE-gamma 1 was constructed by ligating an EcoRI and BglII fragment of pBR322-CESSV(CE-1) containing the VDJ region with an EcoRI and BamHI fragment of Ch4A-HIg gamma 1-10 containing the gamma 1 constant region. About 200 copies of Ch4A-VCE-gamma 1 genes were introduced into fertilized mouse eggs. Of 489 eggs injected with these genes, 319 survived and were transferred to oviducts of foster mothers. Thirtyeight mice were born and were screened for the presence of human gamma 1 immunoglobulin genes by Southern blot hybridization. Five of these 38 mice had integrated human gamma 1 immunoglobulin genes. None of the human gamma 1 copies in each mouse had undergone deletions or rearrangements as judged by the Southern blotting patterns for several restriction enzymes. Human gamma 1 gene was present in several different tissues. All the mice tested so far transmit the human gamma 1 gene to a fraction of their offspring in an autosomal dominant manner. Spleen cells from transgenic mice were analyzed for immunoglobulin production by reverse plaque assay or immunofluorescence staining of cytoplasmic immunoglobulin, but synthesis and secretion of human gamma 1 chains could not be detected. No human gamma 1 immunoglobulin mRNA was detected in the liver and spleen of a transgenic mouse. The presence of the human gamma 1 immunoglobulin gene appeared to have no effect on the expression of endogenous mouse immunoglobulin genes.

  9. Guidelines for the use of human immunoglobulin therapy in patients with primary immunodeficiencies in Latin America.

    PubMed

    Condino-Neto, A; Costa-Carvalho, B T; Grumach, A S; King, A; Bezrodnik, L; Oleastro, M; Leiva, L; Porras, O; Espinosa-Rosales, F J; Franco, J L; Sorensen, R U

    2014-01-01

    Antibodies are an essential component of the adaptative immune response and hold long-term memory of the immunological experiences throughout life. Antibody defects represent approximately half of the well-known primary immunodeficiencies requiring immunoglobulin replacement therapy. In this article, the authors review the current indications and therapeutic protocols in the Latin American environment. Immunoglobulin replacement therapy has been a safe procedure that induces dramatic positive changes in the clinical outcome of patients who carry antibody defects. PMID:23333411

  10. Computational study on the interactions and orientation of monoclonal human immunoglobulin G on a polystyrene surface

    PubMed Central

    Javkhlantugs, Namsrai; Bayar, Hexig; Ganzorig, Chimed; Ueda, Kazuyoshi

    2013-01-01

    Having a theoretical understanding of the orientation of immunoglobulin on an immobilized solid surface is important in biomedical pathogen-detecting systems and cellular analysis. Despite the stable adsorption of immunoglobulin on a polystyrene (PS) surface that has been applied in many kinds of immunoassays, there are many uncertainties in antibody-based clinical and biological experimental methods. To understand the binding mechanism and physicochemical interactions between immunoglobulin and the PS surface at the atomic level, we investigated the binding behavior and interactions of the monoclonal immunoglobulin G (IgG) on the PS surface using the computational method. In our docking simulation with the different arrangement of translational and rotational orientation of IgG onto the PS surface, three typical orientation patterns of the immunoglobulin G on the PS surface were found. We precisely analyzed these orientation patterns and clarified how the immunoglobulin G interacts with the PS surface at atomic scale in the beginning of the adsorption process. Major driving forces for the adsorption of IgG onto the PS surface come from serine (Ser), aspartic acid (Asp), and glutamic acid (Glu) residues. PMID:23874096

  11. Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.

    PubMed Central

    Nicoletti, A; Kaveri, S; Caligiuri, G; Bariéty, J; Hansson, G K

    1998-01-01

    Atherosclerosis is associated with immune activation. T cells and macrophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced atherosclerosis, congenital deficiency of macrophages, lymphocytes, or interferon-gamma receptors result in reduced lesion formation. We have now evaluated whether immune modulation in the adult animal affects disease development. Injections of 7-wk-old male apo E knockout mice with polyclonal immunoglobulin preparations (ivIg) during a 5-d period reduced fatty streak formation over a 2-mo period on cholesterol diet by 35%. Fibrofatty lesions induced by diet treatment for 4 mo were reduced by 50% in mice receiving ivIg after 2 mo on the diet. ivIg treatment also reduced IgM antibodies to oxidized LDL and led to inactivation of spleen and lymph node T cells. These data indicate that ivIg inhibits atherosclerosis, that it is effective both during the fatty streak and plaque phases, and that it may act by modulating T cell activity and/or antibody production. Therefore, immunomodulation may be an effective way to prevent and/or treat atherosclerosis. PMID:9727059

  12. Targeted disruption of the porcine immunoglobulin kappa light chain locus.

    PubMed

    Ramsoondar, J; Mendicino, M; Phelps, C; Vaught, T; Ball, S; Monahan, J; Chen, S; Dandro, A; Boone, J; Jobst, P; Vance, A; Wertz, N; Polejaeva, I; Butler, J; Dai, Y; Ayares, D; Wells, K

    2011-06-01

    Inactivation of the endogenous pig immunoglobulin (Ig) loci, and replacement with their human counterparts, would produce animals that could alleviate both the supply and specificity issues of therapeutic human polyclonal antibodies (PAbs). Platform genetics are being developed in pigs that have all endogenous Ig loci inactivated and replaced by human counterparts, in order to address this unmet clinical need. This report describes the deletion of the porcine kappa (κ) light chain constant (Cκ) region in pig primary fetal fibroblasts (PPFFs) using gene targeting technology, and the generation of live animals from these cells via somatic cell nuclear transfer (SCNT) cloning. There are only two other targeted loci previously published in swine, and this is the first report of a targeted disruption of an Ig light chain locus in a livestock species. Pigs with one targeted Cκ allele (heterozygous knockout or ±) were bred together to generate Cκ homozygous knockout (-/-) animals. Peripheral blood mononuclear cells (PBMCs) and mesenteric lymph nodes (MLNs) from Cκ -/- pigs were devoid of κ-containing Igs. Furthermore, there was an increase in lambda (λ) light chain expression when compared to that of wild-type littermates (Cκ +/+). Targeted inactivation of the Ig heavy chain locus has also been achieved and work is underway to inactivate the pig lambda light chain locus.

  13. Tc-99m polyclonal human immunoglobulin scintigraphy in brucellosis.

    PubMed

    Kadanali, A; Varoglu, E; Kerek, M; Tasyaran, M A

    2005-06-01

    The aim of this study was to evaluate the accuracy of Tc-99m polyclonal human immunoglobulin (HIG) scintigraphy for the diagnosis of brucellosis, and to compare its effectiveness in the diagnosis of osteoarticular involvement in comparison with bone scanning. Of 30 patients with brucellosis, Tc-99m HIG detected osteoarticular involvement in 18 (60%) patients, in whom the sacroiliac joints were affected most commonly (n = 13; 72.2%), with statistically predominant bilateral involvement (p < 0.05). By bone scanning, the rate of osteoarticular involvement was 70% (21 of 30 patients), and the joints affected most commonly were sacroiliac (15 of 21 patients; 71.4%). Although bilateral involvement was observed mostly by bone scanning, there was no significant difference between the rate of bilateral and unilateral involvement. The anatomical distribution of osteoarticular complications, as detected by Tc-99m HIG and bone scintigraphy, did not differ significantly. With Tc-99m HIG, orchitis was detected in two patients and paravertebral abscess in one patient. Since bone scanning did not detect these soft tissue complications, Tc-99m HIG scintigraphy might be useful for the detection of both osteoarticular and soft tissue complications resulting from brucellosis.

  14. Specific dimerization of the light chains of human immunoglobulin.

    PubMed

    Stevenson, G T; Straus, D

    1968-07-01

    1. The light chains of human immunoglobulin were allowed to dimerize in vitro on removal of the dispersing agents acetic acid or urea. 2. On electrophoresis in polyacrylamide gel at pH8.8 the dimers yielded up to nine regularly spaced bands. This approximates to the number of electrophoretic components known to occur among the monomers. 3. Single electrophoretic components of the dimers were isolated from the gel, dissociated into monomers, and subjected as such to electrophoresis in urea-containing gels. Each gave two adjacent bands. 4. Similarly, after all the light chains as monomers had been subjected to electrophoresis in urea-containing gels, single electrophoretic components were isolated and allowed to dimerize. When examined now as dimers in the absence of urea, each component gave two adjacent bands. 5. These findings are explicable on the following basis. (a) The dimerization of the light chains is specific, at least inasmuch as it occurs between monomers of the same electrophoretic mobilities. (b) With the buffer constant, different light chains undergo different changes in net charge on being transferred from urea-containing to urea-free solution; in this way two different chains of the same initial charge can acquire a charge difference of 1. 6. Experiments with Bence-Jones proteins and other homogeneous light chains gave results substantiating the conclusions (a) and (b). PMID:4174431

  15. New Insights into the Enigma of Immunoglobulin D

    PubMed Central

    Chen, Kang; Cerutti, Andrea

    2011-01-01

    Summary Immunoglobulin D (IgD) has remained a mysterious antibody class for almost half a century. IgD was initially thought to be a recently evolved Ig isotype expressed only by some mammalian species, but recent discoveries in fishes and amphibians demonstrate that IgD was present in the ancestor of all jawed vertebrates and has important immunological functions. The structure of IgD has been very dynamic throughout evolution. Mammals can express IgD through alternative splicing and class switch recombination (CSR). Active cell-dependent and T-cell-independent IgM-to-IgD class switching takes place in a unique subset of human B cells from the upper aerodigestive mucosa, which provides a layer of mucosal protection by interacting with many pathogens and their virulence factors. Circulating IgD can bind to myeloid cells such as basophils and induce antimicrobial, inflammatory, and B-cell-stimulating factors upon cross-linking, which contributes to immune surveillance but also inflammation and tissue damage when this pathway is overactivated under pathological conditions. Recent research shows that IgD is an important immunomodulator that orchestrates an ancestral surveillance system at the interface between immunity and inflammation. PMID:20727035

  16. IV immunoglobulin confounds JC virus antibody serostatus determination

    PubMed Central

    Kuesters, Geoffrey; Chamot, Eric; Omari, Mirza; Dontas, Kim; Yarussi, Mary; Subramanyam, Meena; Herbert, Joseph

    2014-01-01

    Objective: To determine the impact of therapeutic infusion of IV immunoglobulin (IVIg) on John Cunningham virus antibody (JCV Ab) serostatus and level in serum. Methods: We carried out a retrospective analysis of serum levels of JCV Ab among STRATIFY-2 trial enrollees from 2 multiple sclerosis centers who were exposed to IVIg during the trial. For the subset of eligible patients, we estimated mean linear trends while on IVIg and after stopping IVIg with a linear mixed-effects model. Results: The JCV Ab seropositivity rate in the group of patients that was recently exposed to IVIg was 100%, which is significantly higher than in the IVIg-naive population (58%, p < 0.001). The seropositivity rate in the patient group with remote IVIg exposure was similar to that in the IVIg-naive population (67%, p = 0.68, Fisher exact test). The slope of the linear trend line after stopping IVIg decreased significantly by −0.310 units per 100 days (95% confidence interval, −0.611 to −0.008; p = 0.04). Conclusions: Recent IVIg exposure is invariably associated with JCV Ab seropositivity. After stopping IVIg, JCV Ab levels tend to decrease with time, and seroreversion to innately Ab-negative status can occur. PMID:25340081

  17. Evaluation of immunoglobulins in bovine colostrum using laser induced fluorescence.

    PubMed

    Abdel-Salam, Z; Abdel Ghany, Sh; Harith, M A

    2014-11-01

    The objective of the present study was to exploit laser induced fluorescence (LIF) as a spectrochemical analytical technique for evaluation of immunoglobulin (IgG) in bovine colostrum. Colostrum samples were collected from different American Holstein cows at different times after calving. Four samples were gathered from each cow; the first three samples were obtained from the first three milkings (colostrum) and the fourth sample (milk) was obtained a week after calving. It has been demonstrated that LIF can be used as a simple, fast, sensitive and less costly spectrochemical analytical technique for qualitative estimation of IgG in colostrum. LIF results have been confirmed via the quantitative evaluation of IgG in the same samples adopting the single radial immunodiffusion conventional technique and a very good agreement has been obtained. Through LIF it was possible to evaluate bovine colostrum after different milking times and to differentiate qualitatively between colostrum from different animals which may reflect their general health status. A fluorescence linear calibration curve for IgG concentrations from 0 up to 120 g L(-1) has been obtained. In addition, it is feasible to adopt this technique for in situ measurements, i.e. in dairy cattle farms as a simple and fast method for evaluation of IgG in bovine colostrum instead of using lengthy and complicated conventional techniques in laboratories. PMID:25127559

  18. Extracellular idiotypic immunoglobulin arising from human leukemic B lymphocytes

    PubMed Central

    1980-01-01

    The peripheral blood lymphocytes of nine out of nine patients with typical surface Ig-positive chronic lymphocytic leukemia but no paraprotein visible on serum electrophoresis have been shown by radioimmunoassay to export small amounts of pentameric IgM during culture (in the range of 2.4-7.2 ng/10(7) cells per h); three out of nine also exported monomeric IgD (0.7-1.4 ng/10(7) cells per h). Immunoglobulin turned over on the cell surface did not appear to contribute to material in the culture fluid, except possibly as vesicle- bound Ig. In three cases, which included two of the IgD producers, anti- idiotypic antibody raised against the cell surface Fab mu was used to demonstrate the idiotypic nature of the exported Ig. Anti-idiotypic antibody was also used to measure levels of idiotypic Ig in the sera of these three patients as a proportion of the total Ig. Total serum IgM was depressed in all three patients, and the idiotypic IgM represented 43%, 65%, and 96% of the IgM. The findings suggest that in typical chronic lymphocytic leukemia involving B lymphocytes, the export of a small amount of idiotypic Ig by the neoplastic cells in a common or even usual occurrence. PMID:6969771

  19. Immunoglobulin genomics in the prairie vole (Microtus ochrogaster).

    PubMed

    Qin, Tong; Zhao, Huijing; Zhu, Huabin; Wang, Dong; Du, Weihua; Hao, Haisheng

    2015-08-01

    In science, the prairie voles are ideal models for studying the regulatory mechanisms of social behavior in humans. The utility of the prairie vole as a biology model can be further enhanced by characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the prairie vole immunoglobulin heavy and light chain genes. The prairie vole IgH locus on chromosome 1 spans over 1600kb, and consists of at least 79 VH segments (28 potentially functional genes, 2 ORFs and 49 pseudogenes), 7 DH segments, 4 JH segments, four constant region genes (μ, γ, ɛ, and α), and two transmembrane regions of δ gene. The Igκ locus, found on three scaffolds (JH996430, JH996605 and JH996566), contains a totle of 124 Vκ segments (47 potentially functional genes, 1 ORF and 76 pseudogenes), 5 Jκ segments and a single Cκ gene. Two different transcriptional orientations were determined for these Vκ gene segments. In contrast, the Igλ locus on scaffold JH996473 and JH996489 includes 21 Vλ gene segments (14 potentially functional genes, 1 ORF and 6 pseudogenes), all with the same transcriptional polarity as the downstream Jλ-Cλ cluster. Phylogenetic analysis and sequence alignments suggested the prairie vole's large germline VH, Vκ and Vλ gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves.

  20. Pioneer oral streptococci produce immunoglobulin A1 protease.

    PubMed Central

    Cole, M F; Evans, M; Fitzsimmons, S; Johnson, J; Pearce, C; Sheridan, M J; Wientzen, R; Bowden, G

    1994-01-01

    As part of a longitudinal study of the relationship between bacterial colonization and the secretory immune response, 367 isolates of pioneer viridans streptococci collected from 40 breast- and bottle-fed neonates within the first month postpartum were tested for the production of immunoglobulin A1 (IgA1) protease and glycosidases. Fifty percent of the streptococci isolated produced IgA1 protease, including all isolates of Streptococcus oralis and S. sanguis, 60.7% of S. mitis biovar 1 isolates, and some isolates that could not be identified. Three cleavage patterns of alpha 1 heavy chains were observed. Six isolates of S. mitis biovar 1 that did not produce IgA1 protease attacked the alpha 1 chain. Incubation of IgA1 protease-negative S. mitis biovar 1 isolates with IgA1, either prior to or together with S. sanguis, rendered the IgA1 paraprotein resistant to cleavage by the IgA1 protease of S. sanguis. The ability of some pioneer streptococci in the human oral cavity to produce IgA1 protease and of others to modify the susceptibility of IgA1 to cleavage by IgA1 protease perhaps enhances their ability to survive in this habitat. Images PMID:8188337

  1. Suppression of experimental autoimmune encephalomyelitis by intravenously administered polyclonal immunoglobulins.

    PubMed

    Achiron, A; Mor, F; Margalit, R; Cohen, I R; Lider, O; Miron, S

    2000-11-01

    Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats either by active immunization with myelin basic protein (MBP) or by adoptive transfer using anti-MBP specific CD4(+)T cells. Treatment with human polyclonal immunoglobulins (IgG) effectively suppressed active EAE. Time-dependent experiments demonstrated that the effect of IgG was manifested only when treatment was given immediately after immunization; administration from day 7 after disease induction did not suppress the disease. In the adoptive transfer model of EAE, IgG had no effect in vivo. However, pretreatment in vitro of the antigen-specific T-cells with IgG inhibited their ability to mediate adoptive EAE, as it did in active EAE. Similarly, in vitro IgG pretreatment of the antigen-specific T-cells suppressed the proliferative response to MBP. Fluorescent Activated Cell Sorter (FACS) analysis demonstrated the binding of IgG to activated T-cell lines that was inhibited by soluble Fc molecules. The differential effects of IgG on active EAE and on the adoptive transfer of EAE suggest that IgG in vivo can suppress disease by acting during the early phase of the immune response which involves naive T cells. The inhibition of T-cell proliferation and adoptive transfer of EAE by incubation of T cells in vitro appears to require higher concentrations of IgG than those obtained in vivo. PMID:11040073

  2. Effects of pseudopregnancy on immunoglobulin-secreting cells in mice.

    PubMed

    Sulila, P; Lundkvist, U; Mattsson, R

    1988-07-01

    Pregnant mice characteristically show elevated numbers of immunoglobulin-secreting cells in their enlarged spleen and para-aortic lymph nodes. A comparative study of pseudopregnancy and syngeneic pregnancy in CBA/Ca mice was made to evaluate the role of maternal hormones in the induction of these changes. To induce pseudopregnancy, CBA/Ca female mice were mated with vasectomized males, the duration of pseudopregnancy induced in this way is 8-10 days. Serum progesterone levels were monitored periodically throughout pseudopregnancy using RIA technique. Changes were recorded in weight of the thymus, spleen and para-aortic lymph nodes, levels of serum IgG and IgM (ELISA-technique), and content of splenic IgG- and IgM-secreting cells (protein A plaque assay). Thymus involution was observed in pregnant and pseudopregnant mice. Patterns of change in the weight of the spleen and the para-aortic lymph nodes (PALN) were similar in pregnant and pseudopregnant mice until day 8. Ig-secretion in the spleen increased slightly day 5-8 in both pregnant and pseudopregnant mice, but to a lesser extent in the latter. No differences were observed in serum Ig levels between the two groups until day 8. A marked decrease in serum IgG levels and, to some extent, IgM levels between days 8 and 12 was observed in pregnant animals.

  3. Local Immunoglobulin E in the Nasal Mucosa: Clinical Implications

    PubMed Central

    De Schryver, Els; Devuyst, Lien; Derycke, Lara; Dullaers, Melissa; Van Zele, Thibaut; Bachert, Claus

    2015-01-01

    Immunoglobulin E (IgE) can be highly elevated in the airway mucosa independently of IgE serum levels and atopic status. Mostly, systemic markers are assessed to investigate inflammation in airway disease for research or clinical practice. A more accurate but more cumbersome approach to determine inflammation at the target organ would be to evaluate markers locally. We review evidence for local production of IgE in allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Diagnostic and therapeutic consequences in clinical practice are discussed. We describe that the airway mucosa has the intrinsic capability to produce IgE. Moreover, not only do IgE-positive B cells reside within the mucosa, but all tools are present locally for affinity maturation by somatic hypermutation (SHM), clonal expansion, and class switch recombination to IgE. Recognizing local IgE in the absence of systemic IgE has diagnostic and therapeutic consequences. Therefore, we emphasize the importance of local IgE in patients with a history of AR or CRSwNP. PMID:25749769

  4. Mechanism of immunoglobulin G adsorption on polystyrene microspheres.

    PubMed

    Sofińska, Kamila; Adamczyk, Zbigniew; Barbasz, Jakub

    2016-01-01

    The adsorption of polyclonal immunoglobulin G (IgG) on negatively charged polystyrene microparticle suspension (latex) was studied by using the Laser Doppler Velocimetry (LDV) measurements. Using this technique, the dependence of the electrophoretic mobility of particles on the IgG concentration in the suspension was measured for various ionic strengths and pH 3.5. The increase in the electrophoretic mobility was quantitatively interpreted in terms of the 3D electrokinetic model. On the other hand, the maximum coverage of IgG on latex was determined using the depletion method based on AFM imaging. It was shown that IgG adsorption was irreversible and that its maximum coverage on the microspheres increased from 1.4mgm(-2) for 0.001M NaCl to 2.0mgm(-2) for 0.15M NaCl. This was interpreted in terms of reduced electrostatic repulsion among adsorbed molecules. The stability of IgG monolayers on the particles was confirmed in separate experiments where changes in its electrophoretic mobility were monitored over prolonged time periods. Additionally, the acid-base properties of the IgG monolayers on latex were determined in pH cycling experiments. The isoelectric point of the IgG monolayers on the microspheres was 4.8. The results obtained in this work indicate that basic physicochemical characteristics of IgG can be acquired via electrophoretic mobility measurements using microgram quantities of the protein.

  5. Cytomegalovirus Hyper Immunoglobulin for CMV Prophylaxis in Thoracic Transplantation.

    PubMed

    Rea, Federico; Potena, Luciano; Yonan, Nizar; Wagner, Florian; Calabrese, Fiorella

    2016-03-01

    Cytomegalovirus (CMV) infection negatively influences both short- and long-term outcomes after cardiothoracic transplantation. In heart transplantation, registry analyses have shown that CMV immunoglobulin (CMVIG) with or without virostatic prophylaxis is associated with a significant reduction in mortality and graft loss versus no prophylaxis, particularly in high-risk donor (D)+/recipient (R)- transplants. Randomized comparative trials are lacking but retrospective data suggest that addition of CMVIG to antiviral prophylaxis may reduce rates of CMV-related events after heart transplantation, including the incidence of acute rejection or chronic allograft vasculopathy. However, available data consistently indicate that when CMVIG is used, it should be administered with concomitant antiviral therapy, and that evidence concerning preemptive management with CMVIG is limited, but promising. In lung transplantation, CMVIG should again only be used with concomitant antiviral therapy. Retrospective studies have shown convincing evidence that addition of CMVIG to antiviral prophylaxis lowers CMV endpoints and mortality. The current balance of evidence suggests that CMVIG prophylaxis reduces the risk of bronchiolitis obliterans syndrome, but a controlled trial is awaited. Overall, the relatively limited current data set suggests that prophylaxis with CMVIG in combination with antiviral therapy appears effective in D+/R- heart transplant patients, whereas in lung transplantation, addition of CMVIG in recipients of a CMV-positive graft may offer an advantage in terms of CMV infection and disease.

  6. Immunoglobulin A nephropathy: current progress and future directions.

    PubMed

    Zhang, Chunlei; Zeng, Xuehui; Li, Zhongxin; Wang, Zhe; Li, Shunmin

    2015-08-01

    Immunoglobulin A (IgA) nephropathy is the most prevalent form of primary glomerulonephritis that often leads to end-stage kidney failure, thereby representing a major health challenge worldwide. Tremendous effort has been dedicated to the diagnosis, monitoring, and treatment of the disease, and the past several years have witnessed exciting advances that have enriched our understanding of the biology, etiology, and pathology of IgA nephropathy. The disease is characterized by predominant deposition of IgA immune complexes that progressively causes activation of mesangial cells, glomerular inflammation, and ultimately renal injury. Multiple recent independent high-throughput studies in cohorts have identified key susceptibility alleles, such as the major histocompatibility complex loci that are significantly associated with the risk of disease occurrence. Notably, a fraction of these risk loci encode proteins that participate in immune defense against mucosal pathogens, particularly intestinal nematodes, indicating a linkage between IgA-mediated antihelminth immunity and the pathogenesis of IgA nephropathy. The emerging "omics" technology also allows for systemic analysis of urinary and serum samples as a noninvasive procedure for diagnosis and prognosis, as demonstrated by several studies implicating the proteomic signature and microRNA profile as promising diagnostic and prognostic parameters. In the clinic, the current treatment protocol relies on suppression of the renin-angiotensin system to control blood pressure and proteinuria. This review scrutinizes and summarizes recent relevant findings that aim to translate researchers' benchside knowledge of disease initiation and development into patients' bedside diagnosis and therapy. PMID:25797891

  7. Immunoglobulin determinants on the lymphocytes of normal rabbits

    PubMed Central

    Coombs, R. R. A.; Gurner, B. W.; Janeway, C. A.; Wilson, Anne B.; Gell, P. G. H.; Kelus, A. S.

    1970-01-01

    Immunoglobulin determinants can be shown on the membrane of circulating lymphocytes of the rabbit by the mixed antiglobulin reaction. An enumeration was made of lymphocytes reacting specifically with anti-γ, anti-μ, anti-Fab and anti-L chain sera. The L chain allotypic determinants As4 and As6 were also shown and reacting cells enumerated. There was a marked dose-dependence between the concentration of the antiglobulin reagent used to treat the lymphocyte suspension and the number of lymphocytes reacting to form rosettes. The experiments reported at this stage bear no direct evidence on the question as to whether the μ- and γ-determinants, or more than one L chain allotypic determinant can exist on the one cell. Of three rabbits with 26, 47, and 61 per cent IgG-reacting lymphocytes in the circulation, only one had 1 per cent reacting cells in the thymus while the other two had less than 1 per cent. No μ-reacting cells were detectable in the thymuses of the two rabbits tested. ImagesFIG. 2 PMID:4192262

  8. Immunoglobulin G response in patients with Campylobacter concisus diarrhea.

    PubMed

    Nielsen, Hans Linde; Kaakoush, Nadeem O; Mitchell, Hazel M; Nielsen, Henrik

    2016-02-01

    Limited information is available on the systemic immunoglobulin response in patients infected with the emerging pathogen Campylobacter concisus. The aim of the present study was to detect anti-C. concisus antibodies in serum of 88 patients with C. concisus gastroenteritis. Specific IgG antibodies to C. concisus were measured in serum using an in-house enzyme-linked immunosorbent assay, and pooled donor serum was used as a control. The mean optical density was 0.135 (SEM: 0.020) for the 88 adult patients and 0.100 (SEM: 0.011) in controls. When using an optical density value equal to the mean +3 SEM for the control serum, 22 (25%) C. concisus-positive patients had increased IgG antibodies. Patients with high IgG levels more often reported headache, and they had a trend toward more mucus in stools, whereas IgG levels were unrelated to age, duration of diarrhea, number of stools per day, and weight loss.

  9. Comparison of somatic mutation frequency among immunoglobulin genes.

    PubMed

    Motoyama, N; Miwa, T; Suzuki, Y; Okada, H; Azuma, T

    1994-02-01

    We analyzed the frequency of somatic mutation in immunoglobulin genes from hybridomas that secrete anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) monoclonal antibodies. A high frequency of mutation (3.3-4.4%) was observed in both the rearranged VH186.2 and V lambda 1 genes, indicating that somatic mutation occurs with similar frequency in these genes in spite of the absence of an intron enhancer in lambda 1 chain genes. In contrast to the high frequency in J-C introns, only two nucleotide substitutions occurred at positions -462 and -555 in the 5' noncoding region in one of the lambda 1-chain genes and in none of the other three so far studied. Since a similar low frequency of somatic mutation was observed in the 5' noncoding region of inactive lambda 2-chain genes rendered inactive because of incorrect rearrangement, this region may not be a target or alternatively, may be protected from the mutator system. We observed a low frequency of nucleotide substitution in unrearranged V lambda 1 genes (approximately 1/15 that of rearranged genes). Together with previous results (Azuma T., N. Motoyama, L. Fields, and D. Loh, 1993. Int. Immunol. 5:121), these findings suggest that the 5' noncoding region, which contains the promoter element, provides a signal for the somatic mutator system and that rearrangement, which brings the promoter into close proximity to the enhancer element, should increase mutation efficiency.

  10. Somatic hypermutation of immunoglobulin genes in human neonates.

    PubMed

    Ridings, J; Nicholson, I C; Goldsworthy, W; Haslam, R; Roberton, D M; Zola, H

    1997-05-01

    The antibody response in the young infant is limited in several ways; in particular, responses generally are of low affinity and restricted to IgM. This raises the question whether the affinity maturation process, consisting of somatic mutation of immunoglobulin genes coupled with selection of high-affinity variants, is operative in the neonate. Re-arranged V(H)6 genes were amplified by polymerase chain reaction (PCR) from cord blood and from peripheral blood of infants. Heteroduplex analysis detected mutation in only 2/18 cord blood samples, while mutations were seen from about 10 days of age onwards. Cloning and sequencing of mutated neonatal V(H)6 genes showed that mutated sequences contained relatively few mutations (one to three mutations per sequence) compared with published values of about 10 in adult IgM sequences. Selection was not evident in the majority of neonatal samples. Thus mutation can occur in the human neonate, but is minimal and generally not accompanied by selection. The age at which affinity maturation develops effectively is yet to be defined.

  11. The immunoglobulin genes: structure and specificity in chronic lymphocytic leukemia.

    PubMed

    Tobin, Gerard

    2007-06-01

    The rearrangement of the immunoglobulin genes (IG) provides a large diversity of B-cell receptors conformations and allows the immune system to respond differently to foreign antigens. In chronic lymphocytic leukemia (CLL), there are a restricted number of stereotyped B-cell receptors rearranged by the tumor B-cells between CLL patients. These subsets with stereotyped receptors appear to have clinical implications, for example cases that rearrange the IGHV3-21 gene display poor clinical prognosis. The number of subsets with stereotyped receptors has been reported at a frequency of over 20% of CLL cases; however, the specificities of these receptors are still not clearly defined. Reactivity to epitopes from bacterial antigen, cytoskeleton components such as vimentin, and antigens on viable and apoptotic T-cell have been proposed. The role of antigen in CLL development is currently being more clearly defined with identification of stereotyped receptors, and their antigen specificity and the continued role antigen stimulation plays in CLL disease will be an important question in the future.

  12. Tailoring immobilization of immunoglobulin by excimer laser for biosensor applications.

    PubMed

    Sima, Felix; Axente, Emanuel; Ristoscu, Carmen; Mihailescu, Ion N; Kononenko, Taras V; Nagovitsin, Ilya A; Chudinova, Galina; Konov, Vitaly I; Socol, Marcela; Enculescu, Ionut; Sima, Livia E; Petrescu, Stefana M

    2011-02-01

    The sheltered transfer and immobilization of rabbit anti-human antiserum immunoglobulin G (IgG) by matrix-assisted pulsed laser evaporation (MAPLE) are reported. The iced targets submitted to laser irradiation consisted of 0.2-2 mg/mL IgG blended or not with lipid (L-α-phosphatidylcholine dipalmitoyl) dissolved in distilled water-based saline buffer. Thin IgG coatings were obtained at room temperature onto glass, fused silica, or silicon substrates. Ten thousand subsequent laser pulses of 0.33, 0.5, or 0.67 J/cm(2) fluence were applied for the synthesis of each sample. Morphology and composition of the thin films were studied by optical, scanning, and atomic force microscopy and Fourier transformed infrared spectrometry. Optical labeling methods such as spectrofluorimetry and fluorescence microscopy were selected to verify the biosensor transduction principle because of their high sensitivity for detecting low amounts of antigen (IgG). Protein immobilization to the substrate surface was demonstrated for all obtained structures after immersion in the donkey anti-rabbit secondary antibody solution. The IgG transfer and immobilization onto substrates were improved by addition of lipid to MAPLE solutions.

  13. Immunoglobulin G4-related disease of the hard palate.

    PubMed

    Andrew, Nicholas; Kearney, Daniel; Sladden, Nicole; Goss, Alastair; Selva, Dinesh

    2014-04-01

    A 71-year-old woman presented with erythematous, nontender, bilateral hard palate nodules of 6-month duration. Biopsy showed collagenous sclerosis and a follicular lymphoplasmacytic infiltrate among the minor salivary glands. Immunoglobulin G (IgG) and IgG4 staining showed 280 IgG4(+) cells per high-power field and a ratio of IgG4(+) to IgG(+) cells of 0.8. The patient subsequently developed bilateral lacrimal gland and parotid gland enlargement associated with an increased serum IgG4 level of 3,031 mg/dL (≤ 135 mg/dL). Left lacrimal gland biopsy confirmed IgG4-related dacryoadenitis. The patient declined corticosteroid treatment for IgG4-related disease (IgG4-RD) and remained stable at 15 months after the first presentation. Spontaneous, partial resolution of the palatal lesion was observed during follow-up. IgG4-RD should be considered in the differential diagnosis of lymphoplasmacytic lesions of the hard palate.

  14. Immunoglobulin genomics in the prairie vole (Microtus ochrogaster).

    PubMed

    Qin, Tong; Zhao, Huijing; Zhu, Huabin; Wang, Dong; Du, Weihua; Hao, Haisheng

    2015-08-01

    In science, the prairie voles are ideal models for studying the regulatory mechanisms of social behavior in humans. The utility of the prairie vole as a biology model can be further enhanced by characterization of the genes encoding components of the immune system. Here, we report the genomic organization of the prairie vole immunoglobulin heavy and light chain genes. The prairie vole IgH locus on chromosome 1 spans over 1600kb, and consists of at least 79 VH segments (28 potentially functional genes, 2 ORFs and 49 pseudogenes), 7 DH segments, 4 JH segments, four constant region genes (μ, γ, ɛ, and α), and two transmembrane regions of δ gene. The Igκ locus, found on three scaffolds (JH996430, JH996605 and JH996566), contains a totle of 124 Vκ segments (47 potentially functional genes, 1 ORF and 76 pseudogenes), 5 Jκ segments and a single Cκ gene. Two different transcriptional orientations were determined for these Vκ gene segments. In contrast, the Igλ locus on scaffold JH996473 and JH996489 includes 21 Vλ gene segments (14 potentially functional genes, 1 ORF and 6 pseudogenes), all with the same transcriptional polarity as the downstream Jλ-Cλ cluster. Phylogenetic analysis and sequence alignments suggested the prairie vole's large germline VH, Vκ and Vλ gene segments appear to form limited gene families. Therefore, this species may generate antibody diversity via a gene conversion-like mechanism associated with its pseudogene reserves. PMID:26073565

  15. Immunoglobulin λ Gene Rearrangement Can Precede κ Gene Rearrangement

    DOE PAGES

    Berg, Jörg; Mcdowell, Mindy; Jäck, Hans-Martin; Wabl, Matthias

    1990-01-01

    Imore » mmunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci: κ and λ .It has been reported that κ loci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearranged λ -chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at the κ locus, and that only upon failure to produce a functional κ chain is there an attempt to rearrange the λ locus; and (b) the stochastic theory, which postulates that rearrangement at the λ locus proceeds at a rate that is intrinsically much slower than that at the κ locus. We show here that λ -chain genes are generated whether or not the κ locus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.« less

  16. Measurement of anticomplementary activity in therapeutic intravenous immunoglobulin preparations.

    PubMed

    Ramasamy, I; Tran, E; Farrugia, A

    1997-03-01

    Anticomplementary activity (ACA) of aggregates in intravenous immunoglobulin preparations (IVIG) was investigated using the modified Kabat and Meyer classical complement consumption method recommended by the European Pharmacopoeia and a C1q-coated microtitre enzyme-linked immunosorbent assay (ELISA). The physical characteristics of aggregates were found to affect complement binding. Aggregates formed by heating IVIG preparations at acid pH bound complement poorly, while aggregates formed by heating IVIG at neutral pH showed high ACA. This suggests that analysis of complement binding capacity provides a level of aggregate characterization of aggregates which is additional to quantitation by High-performance liquid chromatography ((HPLC). The correlation (r = 0.98) between the two tests was good when aggregates formed at neutral pH were compared, but decreased (r = 0.57) when aggregates formed at acid pH were included. A comparison of the results showed that there were no significant differences in the classification of aggregates with acceptable/unacceptable (i.e. pass/fail outcome) values of ACA. Between assay variation (CV = 7.6%) was lower in the ELISA test compared with the complement consumption assay (where percentage binding varied from 78.9% to 100%). Both assays are justified for the evaluation of ACA in therapeutic IVIG. The ELISA had the advantage in being more precise, less dependent on reagent source and requiring less technical expertise.

  17. Immunoglobulins: 25 Years of Immunoinformatics and IMGT-ONTOLOGY

    PubMed Central

    Lefranc, Marie-Paule

    2014-01-01

    IMGT®, the international ImMunoGeneTics information system® (CNRS and Montpellier University) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and IgSF and MhSF superfamilies. IMGT® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences and three-dimensional (3D) structures. The concepts include the IMGT® standardized keywords (identification), IMGT® standardized labels (description), IMGT® standardized nomenclature (classification), IMGT unique numbering and IMGT Colliers de Perles (numerotation). IMGT® comprises seven databases, 15,000 pages of web resources and 17 tools. IMGT® tools and databases provide a high-quality analysis of the IG from fish to humans, for basic, veterinary and medical research, and for antibody engineering and humanization. They include, as examples: IMGT/V-QUEST and IMGT/JunctionAnalysis for nucleotide sequence analysis and their high-throughput version IMGT/HighV-QUEST for next generation sequencing, IMGT/DomainGapAlign for amino acid sequence analysis of IG domains, IMGT/3Dstructure-DB for 3D structures, contact analysis and paratope/epitope interactions of IG/antigen complexes, and the IMGT/mAb-DB interface for therapeutic antibodies and fusion proteins for immunological applications (FPIA). PMID:25521638

  18. Influence of calf genotype on colostral immunoglobulins in Bos taurus and Bos indicus cows and serum immunoglobulins in their calves.

    PubMed

    Vann, R C; Holloway, J W; Carstens, G E; Boyd, M E; Randel, R D

    1995-10-01

    Purebred Bos indicus calves are documented to have lower survival rates than Bos taurus calves. Thus, this study was designed to investigate the possibility that this decreased survival rate may be attributed to dam colostral immunoglobulin (Ig) concentrations and subsequent calf serum Ig concentrations. The specific objective was to determine the effect of breed type of calf on colostrum production, immunoglobulin concentrations in colostrum and calf serum, and availability and absorption efficiency of Ig. Brahman (B) and Angus (A) cattle were reciprocally mated to produce calves of the following types: A x A (n = 8), A x B (n = 9), B x B (n = 11), and B x A (n = 11). At birth, calves were separated from their dams and a blood sample was collected before feeding pooled colostrum (30 mL/kg birth weight) at 1 and 6 h of age. From 6 to 12 h of age, each calf was placed in a box that allowed interaction with the dam but prevented suckling. At 12 h of age, each calf was fed its dam's colostrum and placed with the dam. Additional blood samples were collected at 12, 24, and 48 h after birth. Serum and colostrum samples were analyzed for IgG, IgG1, IgG2, IgM, and IgA using single radial immunodiffusion (RID) assay techniques. The cows were hand-milked after induction of milk letdown with oxytocin at 1 and 12 h after calving. Colostrum volume was recorded, and samples were collected. Brahman cows produced more (P < .001) colostrum at 1 and 12 h than A cows. Total Ig concentrations were obtained by summing IgG, IgG1, IgG2, IgM, and IgA concentrations. Total Ig (P < .02), IgG (P < .005), and IgA (P < .01) concentrations in colostrum were greater in cows producing crossbred calves. Total Ig (P < .006), IgG (P < .02), IgG1 (P < .004), and IgG2 (P < .02) available in colostrum were affected by B x B and A x B breed types of calf. Brahman cows had more Ig available at 1 and 12 h than A cows due to increased production of colostrum. Breed type influenced colostral Ig in cattle

  19. Monoclonal antibodies to snakehead, Channa striata immunoglobulins: detection and quantification of immunoglobulin-positive cells in blood and lymphoid organs.

    PubMed

    Sood, Neeraj; Chaudhary, Dharmendra K; Rathore, Gaurav; Singh, Akhilesh; Lakra, W S

    2011-02-01

    Snakehead Channa striata is an important freshwater food fish in many Southeast Asian countries. Three monoclonal antibodies (C9, C10 and D10) were developed against purified serum immunoglobulins of Channa striata (Cs-Ig) and characterized. C9 and D10 MAbs were specific to heavy chain, while C10 MAb detected only unreduced Cs-Ig in western blotting. In competitive ELISA, C9 and C10 MAbs were specific to C. striata Ig and showed no cross reactivity with serum Ig of other fish species i.e. Channa punctatus, Channa marulius, Clarias batrachus and Labeo rohita. D10 MAb showed reactivity to serum Ig of C. striata and C. marulius. In FACS analysis of gated lymphocytes, the percentage of Ig+ cells detected by C9 MAb was 18.2%, 27.7% and 10.3% in blood, spleen and kidney, respectively (n=3, body weight 500-600 g). However, only a few cells (0.5%) were found to be Ig+ in thymus (n=5). C9 MAb was also successfully employed to demonstrate Ig+ cells in blood smears and formalin fixed sections of spleen and kidney. These findings suggest that the spleen plays an important role in humoral immunity as compared to head kidney. Further, these MAbs can be useful immunological tool in monitoring health status of cultured C. striata.

  20. Persistence of immunoglobulin G and immunoglobulin M antibodies after postnatal rubella infection determined by solid-phase radioimmunoassay.

    PubMed Central

    Meurman, O H

    1978-01-01

    The appearance and persistence of immunoglobulin M (IgM) and IgG antibodies in postnatal rubella infections were studied by employing a solid-phase radioimmunoassay test. Altogether, 222 serial serum specimens from 51 patients with acute rubella infection were tested. Both IgG and IgM antibodies developed rapidly and appeared in all patients within 4 days after the onset of rash. In some patients, the IgM antibodies clearly preceded the IgG antibodies; however, the reverse situation was also noticed in a few cases. The IgG antibodies showed only minor changes after 8 to 10 days from the onset of rash. The IgM titers also reached a maximum level at approximately 8 to 10 days after the onset of rash, after which time a rapid decrease was normally seen. The mean half-life of IgM antibodies after 15 days from the onset of rash was 4.5 days, giving for IgM antibodies persistence times from 43 to approximately 80 days. Two patients with a prolonged IgM antibody response were detected. One of these patients had bilateral arthritis of the knee as a complication, whereas in the other patient no complication caused by rubella virus was detected. The IgM antibody response and its value in diagnosis are discussed. PMID:624770

  1. Intra-uterine infection and cord immunoglobulin M II. Clinical analysis of infants with elevated cord serum immunoglobulin M *

    PubMed Central

    Finkel, Annette; Dent, P. B.; Emrich, W. H.; Gent, M.; Rahim, M. A.

    1974-01-01

    Cord blood immunoglobulin M was measured in 3474 consecutive newborn infants. A group of 147 infants with elevated IgM values (≥19.0 mg./100 ml.) were compared with 92 unselected newborn infants with normal IgM values. One infant with clinically unsuspected congenital rubella was detected in the study group while no cases of intra-uterine infection were found among the controls. A greater proportion of mothers in the study group had a history of viral infection. The study group also contained a larger number of mothers who might be considered to be at greater risk of infection with agents known to cause intra-uterine disease. Follow-up studies at 6 months of age revealed no differences between the two groups aside from an increased incidence of minor motor abnormalities in the study group. While it is recognized that infants with cord blood IgM levels truly in excess of 30 mg./100 ml. may represent a high-risk group with respect to proved or subclinical intra-uterine infection, it is concluded that routine cord blood screening for elevated IgM values is not a high-yield procedure for the detection of intra-uterine infection in our population. PMID:4203457

  2. Binding analysis of carbon nanoparticles to human immunoglobulin G: Elucidation of the cytotoxicity of CNPs and perturbation of immunoglobulin conformations

    NASA Astrophysics Data System (ADS)

    Zhang, Shengrui; Yang, Haitao; Ji, Xiaohui; Wang, Qin

    2016-02-01

    The chemical compositions, sizes and fluorescent properties of synthesized carbon nanoparticles (CNPs) were characterized. Escherichia coli (E. coli) cells were used as a model to study the cytotoxicity of CNPs, and the results of the cellular uptake of CNPs yielded excellent results: the CNPs demonstrated good biocompatibility and were non-toxic to the growth of the E. coli cells. Moreover, to assess the potential toxicity of CNPs to human health, the binding behavior of CNPs with human immunoglobulin G (HIgG) was examined by fluorescence quenching spectroscopy, synchronous fluorescence spectroscopy and circular dichroism spectroscopy under physiological conditions. The fluorescence quenching constants and parameters for the interaction at different temperatures had been calculated according to Scatchard. The thermodynamic parameters, such as enthalpy change (ΔH), entropy change (ΔS) and free energy change (ΔG), were calculated, and the results indicated strong static quenching and showed that van der Waals forces, hydrogen bonds and hydrophobic interactions were the predominant intermolecular forces stabilizing the CNP-HIgG complex. Synchronous fluorescence and circular dichroism spectra provided information regarding the conformational alteration of HIgG in the presence of CNPs. These findings help to characterize the interactions between CNPs and HIgG, which may clarify the potential risks and undesirable health effects of CNPs, as well as the related cellular trafficking and systemic translocation.

  3. Monoclonal antibodies to snakehead, Channa striata immunoglobulins: detection and quantification of immunoglobulin-positive cells in blood and lymphoid organs.

    PubMed

    Sood, Neeraj; Chaudhary, Dharmendra K; Rathore, Gaurav; Singh, Akhilesh; Lakra, W S

    2011-02-01

    Snakehead Channa striata is an important freshwater food fish in many Southeast Asian countries. Three monoclonal antibodies (C9, C10 and D10) were developed against purified serum immunoglobulins of Channa striata (Cs-Ig) and characterized. C9 and D10 MAbs were specific to heavy chain, while C10 MAb detected only unreduced Cs-Ig in western blotting. In competitive ELISA, C9 and C10 MAbs were specific to C. striata Ig and showed no cross reactivity with serum Ig of other fish species i.e. Channa punctatus, Channa marulius, Clarias batrachus and Labeo rohita. D10 MAb showed reactivity to serum Ig of C. striata and C. marulius. In FACS analysis of gated lymphocytes, the percentage of Ig+ cells detected by C9 MAb was 18.2%, 27.7% and 10.3% in blood, spleen and kidney, respectively (n=3, body weight 500-600 g). However, only a few cells (0.5%) were found to be Ig+ in thymus (n=5). C9 MAb was also successfully employed to demonstrate Ig+ cells in blood smears and formalin fixed sections of spleen and kidney. These findings suggest that the spleen plays an important role in humoral immunity as compared to head kidney. Further, these MAbs can be useful immunological tool in monitoring health status of cultured C. striata. PMID:21167285

  4. Immunoglobulin M and immunoglobulin G responses in BALB/c mice to conjugated outer membrane extracts of four Salmonella serotypes.

    PubMed Central

    Kudrna, D A; Teresa, G W; Arnzen, J M; Beard, K S

    1985-01-01

    Outer membranes (OMs) of Salmonella enteritidis, S. anatum, S. typhimurium, and S. infantis were extracted and cross-linked with glutaraldehyde to form a large macromolecular antigen. The antigen consisted of OM proteins and lipopolysaccharide and was designated 4-OMP-LPS. Polyacrylamide gel electrophoresis of extracted OMs from each serotype revealed differences in protein profiles. S. enteritidis and S. infantis possessed a greater variety of proteins than did S. anatum and S. typhimurium. Immunizations with 4-OMP-LPS in phosphate-buffered saline (4-OMP-LPS-C) and 4-OMP-LPS emulsified with muramyl dipeptide in the oil phase of a hexadecane-water emulsion (4-OMP-LPS-MDP) revealed that BALB/c mice were capable of eliciting specific primary and secondary immunoglobulin M (IgM) and IgG responses. Both antigen preparations were capable of eliciting IgM and IgG specific for the cell surfaces of each live Salmonella serotype. Also, 4-OMP-LPS-MDP and 4-OMP-LPS-C were capable of evoking a substantial anamnestic response. Adsorption studies revealed that the combined serotypes had the antigenic capacity to adsorb up to 94% of the antibodies, but 4-OMP-LPS-MDP antibodies were more effectively adsorbed than were 4-OMP-LPS-C antibodies. Adsorption of pooled antiserum with heterologous bacteria yielded a variety of adsorption profiles. PMID:4030094

  5. Frequency Patterns of T-Cell Exposed Amino Acid Motifs in Immunoglobulin Heavy Chain Peptides Presented by MHCs

    PubMed Central

    Bremel, Robert D.; Homan, E. Jane

    2014-01-01

    Immunoglobulins are highly diverse protein sequences that are processed and presented to T-cells by B-cells and other antigen presenting cells. We examined a large dataset of immunoglobulin heavy chain variable regions (IGHV) to assess the diversity of T-cell exposed motifs (TCEMs). TCEM comprise those amino acids in a MHC-bound peptide, which face outwards, surrounded by the MHC histotope, and which engage the T-cell receptor. Within IGHV there is a distinct pattern of predicted MHC class II binding and a very high frequency of re-use of the TCEMs. The re-use frequency indicates that only a limited number of different cognate T-cells are required to engage many different clonal B-cells. The amino acids in each outward-facing TCEM are intercalated with the amino acids of inward-facing MHC groove-exposed motifs (GEM). Different GEM may have differing, allele-specific, MHC binding affinities. The intercalation of TCEM and GEM in a peptide allows for a vast combinatorial repertoire of epitopes, each eliciting a different response. Outcome of T-cell receptor binding is determined by overall signal strength, which is a function of the number of responding T-cells and the duration of engagement. Hence, the frequency of TCEM re-use appears to be an important determinant of whether a T-cell response is stimulatory or suppressive. The frequency distribution of TCEMs implies that somatic hypermutation is followed by T-cell clonal expansion that develops along repeated pathways. The observations of TCEM and GEM derived from immunoglobulins suggest a relatively simple, yet powerful, mechanism to correlate T-cell polyspecificity, through re-use of TCEMs, with a very high degree of specificity achieved by combination with a diversity of GEMs. The frequency profile of TCEMs also points to an economical mechanism for maintaining T-cell memory, recall, and self-discrimination based on an endogenously generated profile of motifs. PMID:25389426

  6. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know?

    PubMed

    Crow, Andrew R; Lazarus, Alan H

    2008-04-01

    Intravenous immunoglobulin (IVIg) has been used for more than 25 years to treat an ever-increasing number of autoimmune diseases including immune thrombocytopenic purpura. Although the exact mechanism of action of IVIg has remained elusive, many theories have been postulated, including mononuclear phagocytic system blockade/inhibition, autoantibody neutralization by anti-idiotype antibodies, pathogenic autoantibody clearance due to competitive inhibition of the neonatal immunoglobulin Fc receptor, cytokine modulation, complement neutralization, and immune complex formation leading to dendritic cell priming. Polyclonal anti-D immunoglobulin is a polyclonal IVIg product enriched for antibodies directed to the RhD antigen on red blood cells and that has also been successfully used to treat immune thrombocytopenia in RhD(+) patients. The primary theory to explain polyclonal anti-D immunoglobulin function has classically been mononuclear phagocytic system blockade, although modulation of Fcgamma receptor expression and/or immunomodulation may also play a role. Work using a murine model of immune thrombocytopenic purpura to further our understanding of the mechanism of action of these 2 therapeutic agents is a focus of this article.

  7. Immunogenic and antigenic epitopes of immunoglobulins I. Cross-reactivity of murine monoclonal antibodies to human IgG with the immunoglobulins of certain animal species.

    PubMed Central

    Jefferis, R; Lowe, J; Ling, N R; Porter, P; Senior, S

    1982-01-01

    Antibody-producing hybridoma clones have been isolated following immunization of mice with human IgG. Twenty-five monoclonal antibodies (nine anti-C gamma 3, fourteen anti-C gamma 2, one anit-kappa and one anti-lambda) were selected for study of their cross-reactivity with the IgG of fifteen mammalian species and chicken immunoglobulin. Each antibody exhibited a unique reaction profile suggesting that human IgG expresses a very large repertoire of immunogenic epitopes. Whilst some antibodies showed a very restricted cross-reactivity profile for others a very wide reactivity profile was observed-including two clones producing autoantibodies. Antibodies demonstrating cross-reactivity between human Fc gamma and 7S chicken immunoglobulin allow its definitive assignment as a homologue of human IgG. Four clones demonstrated specificity for bovine IgG subclass gamma 1 and gamma 2 and the degree of reactivity allows their application to qualitative and quantitative assay systems. These studies suggest new perspectives for the characterization of immunoglobulins and the standardization of anti-immunoglobulin reagents. PMID:6173313

  8. Optimisation of the detection of bacterial proteases using adsorbed immunoglobulins as universal substrates.

    PubMed

    Abuknesha, Ram A; Jeganathan, Fiona; Wildeboer, Dirk; Price, Robert G

    2010-06-15

    Bacterial proteases, Type XXIV from Bacillus licheniformens and Type XIV from Streptomyces griseus, were used to investigate the utility and optimisation of a solid phase assay for proteases, using immunoglobulin proteins as substrates. Immunoglobulins IgA and IgG were adsorbed on to surfaces of ELISA plates and exposed to various levels of the bacterial proteases which led to digestion and desorption of proportional amounts of the immunoglobulins. The assay signal was developed by measuring the remaining proteins on the polystyrene surface with appropriate enzyme-labelled anti-immunoglobulin reagents. The assay was fully optimised in terms of substrate levels employing ELISA techniques to titrate levels of adsorbed substrates and protease analytes. The critical factor which influences assay sensitivity was found to be the substrate concentration, the levels of adsorbed immunoglobulins. The estimated detection limits for protease XXIV and XIV were 10micro units/test and 9micro units/test using IgA as a substrate. EC(50) values were calculated as 213 and 48micro units/test for each protease respectively. Using IgG as a substrate, the estimated detection limits were 104micro units/test for protease XXIV and 9micro units/test for protease XIV. EC(50) values were calculated at 529micro units/test and 28micro units/test for protease XXIV and XIV respectively. The solid phase protease assay required no modification of the substrates and the adsorption step is merely simple addition of immunoglobulins to ELISA plates. Adsorption of the immunoglobulins to polystyrene enabled straightforward separation of reaction mixtures prior to development of assay signal. The assay exploits the advantages of the technical facilities of ELISA technology and commercially available reagents enabling the detection and measurement of a wide range of proteases. However, the key issue was found to be that in order to achieve the potential performance of the simple assay, optimisation of the

  9. Biotherapies in inflammatory ocular disorders: Interferons, immunoglobulins, monoclonal antibodies.

    PubMed

    Saadoun, D; Bodaghi, B; Bienvenu, B; Wechsler, B; Sene, D; Trad, S; Abad, S; Cacoub, P; Kodjikian, L; Sève, P

    2013-05-01

    Biotherapies used in clinical practice for the treatment of ophthalmologic manifestations of systemic diseases include interferons (IFN), intravenous immunoglobulins (IVIG) and monoclonal antibodies (anti-TNF, anakinra, tocilizumab and rituximab). Several open prospective studies have shown the effectiveness of IFN-α (78 to 98% complete remission) for the treatment of severe uveitis in Behcet's disease. IFN is capable of inducing prolonged remission and continued after his arrest, in 20-40% of patients. Side effects (flu-like, psychological effects) limit its use in practice. Anti-TNFα (infliximab and adalimumab) represents an attractive alternative therapeutic in severe uveitis refractory to immunosuppressants, especially in Behcet's disease. They are almost always (>90% of cases) and rapidly effective but their action is often suspensive. Anti-TNFα requires an extended prescription or takes over from another immunosuppressant once ocular inflammation has been controlled. IVIG are used for the treatment of Kawasaki disease and Birdshot disease. Several open or retrospective studies showed their effectiveness for the treatment of severe and refractory cicatricial pemphigoid. Tolerance of IVIG is good but their efficacy is transient. Rituximab showed an efficacy in few observations of various inflammatory eye diseases (uveitis, scleritis and idiopathic inflammatory pseudo-tumors or associated with granulomatosis with polyangiitis) and cicatricial pemphigoid. The risk of infection associated with this biotherapy limits its use in refractory diseases to conventional therapy. Anakinra (a soluble antagonist of IL-1R) showed interesting results in terms of efficiency in one small open study in Behcet's disease. Its safety profile is good and with a quick action that could be interesting for the treatment of severe uveitis.

  10. Immunoglobulin D Multiple Myeloma With Rapidly Progressing Renal Failure.

    PubMed

    Modi, Jwalant; Kamal, Jeanne; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie

    2015-08-01

    Immunoglobulin D (IgD) multiple myeloma (MM) is a very rare form of myeloma affecting less than 2% of all myeloma patients. It has a multiorgan involvement with renal failure being the key feature. We present here a case of IgD MM in a 62-year-old white male, smoker with past medical history of hypertension, who presented to emergency department with complaints of lower abdominal pain, constipation and decreased urination. Physical exam was unremarkable. Laboratory investigation showed S.Cr 5.99 mg/dL, hemoglobin 8.7 g/dL and corrected S.Ca 10.6 mg/dL. Urine dipstick showed 100 protein and TP/Cr ratio was 23. Serology was positive for serum free lambda chain level of 8,947.6 mg/L as well with free κ/λ ratio < 0.01. The results of serum and urine electrophoresis and immunofixation were also supportive of diagnosis of IgD MM. IgD level was remarkably elevated (27,300 mg/L) too. CT scan of abdomen/pelvis was negative for obstructive uropathy. Skeletal survey showed a solitary lytic lesion in the iliac crest. His kidney function deteriorated next day requiring hemodialysis. The bone marrow biopsy was positive for plasma cell hypercellularity (70-80%) and flow cytometry showed 8% monoclonal IgD lambda plasma cells. The patient was started on bortezomib and dexamethasone and he underwent bone marrow transplant 6 months later. He is doing well hematologically now but he remains dialysis-dependent. IgD MM is a very rare disease affecting younger population with poor prognosis; patients often end up on hemodialysis despite better control of the hematological component. PMID:26124916

  11. Glycosylation of Immunoglobulin G: Role of Genetic and Epigenetic Influences

    PubMed Central

    Mangino, Massimo; Bell, Jordana T.; Erte, Idil; Akmačić, Irena; Vučković, Frano; Pučić Baković, Maja; Gornik, Olga; McCarthy, Mark I.; Zoldoš, Vlatka; Spector, Tim D.; Lauc, Gordan; Valdes, Ana M.

    2013-01-01

    Objective To determine the extent to which genetic and epigenetic factors contribute to variations in glycosylation of immunoglobulin G (IgG) in humans. Methods 76  N-glycan traits in circulating IgG were analyzed by UPLC in 220 monozygotic and 310 dizygotic twin pairs from TwinsUK. A classical twin study design was used to derive the additive genetic, common and unique environmental components defining the variance in these traits. Epigenome-wide association analysis was performed using the Illumina 27k chip. Results 51 of the 76 glycan traits studied have an additive genetic component (heritability, h2)≥  0.5. In contrast, 12 glycan traits had a low genetic contribution (h2<0.35). We then tested for association between methylation levels and glycan levels (P<2 x10-6). Among glycan traits with low heritability probe cg08392591 maps to a CpG island 5’ from the ANKRD11 gene, a p53 activator on chromosome 16. Probe cg26991199 maps to the SRSF10 gene involved in regulation of RNA splicing and particularly in regulation of splicing of mRNA precursors upon heat shock. Among those with high heritability we found cg13782134 (mapping to the NRN1L gene) and cg16029957 mapping near the QPCT gene to be array-wide significant. The proportion of array-wide epigenetic associations was significantly larger (P<0.005) among glycans with low heritability (42%) than in those with high heritability (6.2%). Conclusions Glycome analyses might provide a useful integration of genetic and non-genetic factors to further our understanding of the role of glycosylation in both normal physiology and disease. PMID:24324808

  12. Complement and immunoglobulin levels in athletes and sedentary controls.

    PubMed

    Nieman, D C; Tan, S A; Lee, J W; Berk, L S

    1989-04-01

    Eleven marathon runners (42.7 +/- 2.1 yrs, 54.2 +/- 1.8 ml.kg-1.min-1) and nine sedentary controls (44.2 +/- 1.2 yrs, 33.3 +/- 1.1 ml.kg-1.min-1) were studied during 30 min of rest, a graded maximal treadmill test using the Balke protocol, and 45 min of recovery to determine the effects of training and acute exercise on complement and immunoglobulin levels. Three baseline and five recovery blood samples were obtained in addition to repeated 5-min samples during exercise. Data for the exercise period were analyzed using a multiple regression approach to repeated measures ANOVA to allow comparison between groups on a percent VO2max basis. Groups did not differ during any of the three phases for IgG, IgA, or IgM. Resting levels of complement C3 (0.89 +/- 0.05 vs 1.27 +/- 0.10 g/L, P less than 0.001) and C4 (0.19 +/- 0.02 vs 0.29 +/- 0.03 g/L, P less than 0.001) were significantly lower in athletes than in controls. Exercise complement C3 [F(1,18) = 14.1, P = 0.001] and C4 [F(1,18) = 7.6, P = 0.013], and recovery complement [F(1,18) = 19.4, P less than 0.001] and C4 [F(1,18) = 13.5, P = 0.002] were also lower in the athletes than in sedentary controls. Acute increases during exercise were not associated with changes in catecholamines or cortisol. These data suggest that blood concentrations of C3 and C4, but not IgG, IgA, or IgM, are decreased during rest, graded maximal exercise, and recovery in marathon runners in comparison with sedentary controls.

  13. Oral Microbial Ecology and the Role of Salivary Immunoglobulin A

    PubMed Central

    Marcotte, Harold; Lavoie, Marc C.

    1998-01-01

    In the oral cavity, indigenous bacteria are often associated with two major oral diseases, caries and periodontal diseases. These diseases seem to appear following an inbalance in the oral resident microbiota, leading to the emergence of potentially pathogenic bacteria. To define the process involved in caries and periodontal diseases, it is necessary to understand the ecology of the oral cavity and to identify the factors responsible for the transition of the oral microbiota from a commensal to a pathogenic relationship with the host. The regulatory forces influencing the oral ecosystem can be divided into three major categories: host related, microbe related, and external factors. Among host factors, secretory immunoglobulin A (SIgA) constitutes the main specific immune defense mechanism in saliva and may play an important role in the homeostasis of the oral microbiota. Naturally occurring SIgA antibodies that are reactive against a variety of indigenous bacteria are detectable in saliva. These antibodies may control the oral microbiota by reducing the adherence of bacteria to the oral mucosa and teeth. It is thought that protection against bacterial etiologic agents of caries and periodontal diseases could be conferred by the induction of SIgA antibodies via the stimulation of the mucosal immune system. However, elucidation of the role of the SIgA immune system in controlling the oral indigenous microbiota is a prerequisite for the development of effective vaccines against these diseases. The role of SIgA antibodies in the acquisition and the regulation of the indigenous microbiota is still controversial. Our review discusses the importance of SIgA among the multiple factors that control the oral microbiota. It describes the oral ecosystems, the principal factors that may control the oral microbiota, a basic knowledge of the secretory immune system, the biological functions of SIgA, and, finally, experiments related to the role of SIgA in oral microbial ecology

  14. Epitope-specific tolerance induction with an engineered immunoglobulin.

    PubMed Central

    Zambidis, E T; Scott, D W

    1996-01-01

    Isologous and heterologous immunoglobulins have been shown to be extremely effective as tolerogenic carriers for nearly 30 years. The efficacy of these proteins is due in part to their long half-life in vivo, as well as their ability to crosslink surface IgM with Fc receptors. The concept of using IgG as a carrier molecule to induce unresponsiveness in the adult immune system has been exploited for simple haptens, such as nucleosides, as well as for peptides. To further evaluate the in vivo potential of these molecules for inducing tolerance to a defined epitope, we have engineered a fusion protein of mouse IgG1 with the immunodominant epitope 12-26 from bacteriophage lambda cI repressor protein. This 15-mer, which contains both a B-cell and T-cell epitope, has been fused in-frame to the N terminus of a mouse heavy chain IgG1 construct, thus creating a "genetic hapten-carrier" system. We describe a novel in vitro and in vivo experimental system for studying the feasibility of engineered tolerogens, consisting of a recombinant flagellin challenge antigen and a murine IgG1 tolerogen, both expressing the lambda repressor epitope 12-26. Herein, we show that peptide-grafted IgG molecules injected i.v., or expressed by transfected, autologous B cells, can efficiently modulate the cellular and humoral immune responses to immunodominant epitopes. This model displays the feasibility of "tailor-designing" immune responses to whole antigens by selecting epitopes for either tolerance or immunity. Images Fig. 1 Fig. 5 PMID:8643522

  15. Analysis of the immunoglobulin A protease gene of Streptococcus sanguis.

    PubMed Central

    Gilbert, J V; Plaut, A G; Wright, A

    1991-01-01

    The amino acid sequence T-P-P-T-P-S-P-S is tandemly duplicated in the heavy chain of human immunoglobulin A1 (IgA1), the major antibody in secretions. The bacterial pathogen Streptococcus sanguis, a precursor to dental caries and a cause of bacterial endocarditis, yields IgA protease that cleaves only the Pro-Thr peptide bond in the left duplication, while the type 2 IgA proteases of the genital pathogen Neisseria gonorrhoeae and the respiratory pathogen Haemophilus influenzae cleave only the P-T bond in the right half. We have sequenced the entire S. sanguis iga gene cloned into Escherichia coli. A segment consisting of 20 amino acids tandemly repeated 10 times, of unknown function, occurs near the amino-terminal end of the enzyme encoded in E. coli. Identification of a predicted zinc-binding region in the S. sanguis enzyme and the demonstration that mutations in this region result in production of a catalytically inactive protein support the idea that the enzyme is a metalloprotease. The N. gonorrhoeae and H. influenzae enzymes were earlier shown to be serine-type proteases, while the Bacteroides melaninogenicus IgA protease was shown to be a cysteine-type enzyme. The streptococcal IgA protease amino acid sequence has no significant homology with either of the two previously determined IgA protease sequences, that of type 2 N. gonorrhoeae and type 1 H. influenzae. The differences in both structure and mechanism among these functionally analogous enzymes underscore their role in the infectious process and offer some prospect of therapeutic intervention. Images PMID:1987065

  16. Detection of Immunoglobulin Isotypes from Dried Blood Spots

    PubMed Central

    Andersen, Nancy J; Mondal, Tapan Kumar; Preissler, Mark T.; Freed, Brian M.; Stockinger, Sabine; Bell, Erin; Druschel, Charlotte; Buck Louis, Germaine M.; Lawrence, David A.

    2015-01-01

    The study was designed to determine the sensitivity and reproducibility of recovering immunoglobulin (Ig) isotypes (IgG subclasses, IgA, IgE and IgM classes) from dried blood spots (DBS), a methodologic subcomponent of the Upstate KIDS Study. A multiplexed Luminex assay was used for IgG1/2/3/4, IgA and IgM analysis; an ELISA was used for IgE. Plasma samples from de-identified patients were used to compare the Luminex assay with nephelometry, which is routinely used to quantify IgA, IgG and IgM in clinical samples. The IgE ELISA was compared to an immunofluorescence assay. Prior to evaluation of punches from newborn dried blood spots (NDBSs), recoveries of Ig from punches of cord blood DBSs (CBDBSs) vs. plasma from the same cord bloods were compared. Although the recoveries of Ig from plasma and DBSs were not comparable, which could be due to cell lysates in the DBS samples, the analyses were reproducible. Additionally, the levels of IgA, IgG2, IgG4, and IgM recovered from CBDBSs positively correlated with those in plasma. The DBS data is a relative value since it is not equivalent to the plasma concentration. The majority of Ig concentrations recovered from 108 newborns of the Upstate KIDs Study were within the range of newborn plasma Ig levels with the exception of IgG3. The IgG4 values displayed the greatest variance with a wide range (0.01–319 mg/dl), whereas, IgG1 values had the narrowest range (85.2–960.4 mg/dl). PMID:24333851

  17. Immunoglobulin Tau Heavy Chain (IgT) in Flounder, Paralichthys olivaceus: Molecular Cloning, Characterization, and Expression Analyses

    PubMed Central

    Du, Yang; Tang, Xiaoqian; Zhan, Wenbin; Xing, Jing; Sheng, Xiuzhen

    2016-01-01

    Immunoglobulin tau (IgT) is a new teleost immunoglobulin isotype, and its potential function in adaptive immunity is not very clear. In the present study, the membrane-bound and secreted IgT (mIgT and sIgT) heavy chain genes were cloned for the first time and characterized in flounder (Paralichthys olivaceus), and found the nucleic acid sequence were exactly same in the Cτ1–Cτ4 constant domains of mIgT and sIgT, but different in variable regions and the C-terminus. The amino acid sequence of mIgT shared higher similarity with Bovichtus diacanthus (51.2%) and Dicentrarchus labrax (45.0%). Amino acid of flounder IgT, IgM, and IgD heavy chain was compared and the highest similarity was found between IgT Cτ1 and IgM Cμ1 (38%). In healthy flounder, the transcript levels of IgT mRNA were the highest in gill, spleen, and liver, and higher in peripheral blood leucocytes, skin, and hindgut. After infection and vaccination with Edwardsiella tarda via intraperitoneal injection and immersion, the qRT-PCR analysis demonstrated that the IgT mRNA level was significantly upregulated in all tested tissues, with similar dynamic tendency that increased firstly and then decreased, and higher in gill, skin, hindgut, liver, and stomach in immersion than in the injection group, but no significant difference existed in spleen and head kidney between immersion and injection groups. These results revealed that IgT responses could be simultaneously induced in both mucosal and systemic tissues after infection/vaccination via injection and immersion route, but IgT might play a more important role in mucosal immunity than in systemic immunity. PMID:27649168

  18. Immunoglobulin Tau Heavy Chain (IgT) in Flounder, Paralichthys olivaceus: Molecular Cloning, Characterization, and Expression Analyses.

    PubMed

    Du, Yang; Tang, Xiaoqian; Zhan, Wenbin; Xing, Jing; Sheng, Xiuzhen

    2016-01-01

    Immunoglobulin tau (IgT) is a new teleost immunoglobulin isotype, and its potential function in adaptive immunity is not very clear. In the present study, the membrane-bound and secreted IgT (mIgT and sIgT) heavy chain genes were cloned for the first time and characterized in flounder (Paralichthys olivaceus), and found the nucleic acid sequence were exactly same in the Cτ1-Cτ4 constant domains of mIgT and sIgT, but different in variable regions and the C-terminus. The amino acid sequence of mIgT shared higher similarity with Bovichtus diacanthus (51.2%) and Dicentrarchus labrax (45.0%). Amino acid of flounder IgT, IgM, and IgD heavy chain was compared and the highest similarity was found between IgT Cτ1 and IgM Cμ1 (38%). In healthy flounder, the transcript levels of IgT mRNA were the highest in gill, spleen, and liver, and higher in peripheral blood leucocytes, skin, and hindgut. After infection and vaccination with Edwardsiella tarda via intraperitoneal injection and immersion, the qRT-PCR analysis demonstrated that the IgT mRNA level was significantly upregulated in all tested tissues, with similar dynamic tendency that increased firstly and then decreased, and higher in gill, skin, hindgut, liver, and stomach in immersion than in the injection group, but no significant difference existed in spleen and head kidney between immersion and injection groups. These results revealed that IgT responses could be simultaneously induced in both mucosal and systemic tissues after infection/vaccination via injection and immersion route, but IgT might play a more important role in mucosal immunity than in systemic immunity. PMID:27649168

  19. Post-marketing observational study on 5% intravenous immunoglobulin therapy in patients with secondary immunodeficiency and recurrent serious bacterial infections.

    PubMed

    Günther, Georg; Dreger, Bettina

    2013-07-01

    Secondary hypogammaglobulinemia is one of the factors responsible for the increased susceptibility to infection in patients with chronic lymphocytic leukemia (CLL). This study assessed the therapeutic results, concomitant medication and tolerance of administering 5% intravenous immunoglobulin, secondary immunodeficiency and recurrent serious bacterial infections. A single center, post-marketing, observational clinical study was performed on 10 patients with a variety of hematological malignancies (CLL, follicular non-Hodgkin lymphoma, IgM-secreting immunocytoma, IgA plasmacytoma and myelodysplastic syndrome/non-Hodgkin lymphoma) who had been infused with IVIG from June 1994 to May 2009. The clinical benefit of IVIG was assessed by comparing the incidence of bacterial infections before and after starting this therapy. Plasma immunoglobulin concentrations and relevant hematological variables were recorded. For safety assessment, adverse events were monitored. The standard IVIG dosage was approximately 0.35 g/kg body weight every 3-4 weeks. Most patients had normal IgG trough values of >600 mg/dL during the IVIG treatment period. The rate of bacterial infections was reduced from 2.4 per patient in the 3 months before IVIG to 0.7 (0-1.5) per patient per year during IVIG treatment. All patients received concomitant medication, mainly anticancer and anti-anemia therapy (100%). No serious adverse events related to IVIG were observed. The frequency of at least one minor adverse reaction was 1.44% (8/556 infusions). In conclusion, the investigated IVIG preparation was well tolerated and clinically beneficial in reducing the long term rate of serious bacterial infections in patients receiving concomitant treatment for malignant diseases.

  20. Biosynthesis of immunoglobulin A (IgA) and immunoglobulin M (IgM). Requirement for J chain and a disulphide-exchanging enzyme for polymerization

    PubMed Central

    Corte, E. Della; Parkhouse, R. M. E.

    1973-01-01

    Mouse myeloma cells secreting 19S IgM (immunoglobulin M) (MOPC 104E and TEPC 183) or monomer and polymer IgA (immunoglobulin A) (MOPC 315) were incubated with radioactive leucine and the intracellular and secreted immunoglobulins and immunoglobulin subunits were prepared by preparative sucrose-density-gradient centrifugation. Samples were reduced in the presence or absence of isolated J chain, passed over Sephadex G-25 and then incubated at 37°C for 30min with or without a source of disulphide-interchange enzyme. The extent of reassembly of reduced subunits was then evaluated by electrophoresis in polyacrylamide gels. Provided that J chain and the disulphide-interchange enzyme were supplied, both IgM and IgA could be assembled from their respective subunits, obtained by reductive cleavage of polymeric forms. Under similar conditions, assembly of polymeric forms from intracellular or secreted 7S monomer subunits also occurred. Under these conditions polymerization was total, there being no residue of the monomeric form. Reassembly did not occur in the absence of either J chain or the enzyme. All of the J chain released from IgM by reductive cleavage was incorporated back into the reassembled polymer. The J chain is therefore likely to be an essential structural requirement for polymeric immunoglobulins. A variety of controls ruled out non-specific interactions, and further suggested that the amino acid sequence of polypeptide chains determines the specificity of polymerization. The fact that intracellular IgA and IgM monomer subunits known to be deficient in galactose and fucose can be completely polymerized suggests that the addition of carbohydrate does not control polymerization. ImagesFig. 7. PMID:4205352

  1. Pharmacokinetics of a new 10% intravenous immunoglobulin in patients receiving replacement therapy for primary immunodeficiency.

    PubMed

    Wasserman, Richard L; Church, Joseph A; Peter, Hans H; Sleasman, John W; Melamed, Isaac; Stein, Mark R; Bichler, Johann

    2009-06-28

    Intravenous immunoglobulin (IVIg) is used in treating immunodeficiencies and autoimmune or inflammatory disorders. As manufacturing processes and storage can alter IgG molecules, pharmacokinetic assessments are important for new preparations. Thus, we studied pharmacokinetics of IgPro10, a new 10% liquid IVIg product stabilised with l-proline, in patients with common variable immunodeficiency (CVID) and X-linked agammaglobulinaemia (XLA). Patients received IgPro10 for >or=4 months (median dose of 444mg/kg, at 3- or 4-week intervals). Median total IgG serum concentrations increased from 10.2g/l pre-infusion to 23.2g/l at infusion end. Serum IgG concentrations decreased in a biphasic manner; median terminal half-life was 36.6 days. Median half-lives were 33.2 for IgG(1), 36.3 for IgG(2), 25.9 for IgG(3) and 36.4 days for IgG(4). Specific antibody concentrations (anti-CMV, anti-Hemophilus influenzae type B, anti-tetanus toxoid and anti-Streptococcus pneumoniae) decreased with median half-lives of 22.3-30.5 days. IgPro10 pharmacokinetics were similar in patients with CVID and XLA, although patients with CVID showed higher levels of anti-tetanus and anti-S. pneumoniae antibodies than patients with XLA, suggesting residual specific antibody production. IgPro10 pharmacokinetics fulfilled expectations for and were similar to intact IgG products. Administration of IgPro10 at 3- or 4-week intervals achieved sufficient plasma concentrations of total IgG, IgG subclasses and antibodies specific to important pathogens.

  2. [Is the abnormal toxicity test still relevant for the safety of vaccines, sera and immunoglobulins?

    PubMed

    Krämer, Beate; Nagel, Margit; Duchow, Karin; Schwanig, Michael; Cussler, Klaus

    1996-01-01

    The German Pharmacopoeia (DAB) requires the abnormal toxicity test (ATT) using mice and guinea pigs as a non-specific safety test for vaccines, sera and immuno-globulines. The purpose of this project was to investigate the relevance of ATT after the introduction of GMP- and GLP-principles in the manufacturing of biological products. A great variability in the test performance became evident for the different test laboratories, involving the animal number as well as the vaccine dosage administration and test duration. The retrospective analysis of ATT results reveals reasons for the incompatibility of particular preparation groups, vaccine components or additives with the animal species used. There were highly significant differences between the manufacturers and the PEI regarding the frequency of deviating test results for identical test batches. Positive ATT"s never resulted from the insufficient quality of a batch. On the other hand vaccines causing adverse reactions in the target species were not identified by the ATT. For these reasons the abnormal toxicity test is unsuitable to detect harmful batches. The results of the analysis of data show that finally the ATT has always been passed, i.e. there was no retention by the vaccine manufacturers and no refusal by the controlling authorities due to the ATT-results. Considering the present animal model and the questionable transferability of the test results to the target species only a poor reliability is evident. Taking into account aspects of drug safety and animal welfare it is recommended to the DAB to omit the ATT.

  3. A novel diagnostic biosensor for distinguishing immunoglobulin mutated and unmutated types of chronic lymphocytic leukemia.

    PubMed

    Ensafi, Ali A; Amini, Maryam; Rezaei, Behzad; Talebi, Majid

    2016-03-15

    In chronic lymphocytic leukemia (CLL), the immunoglobulin heavy-chain variable (IgVH) region may be mutated (Ig-mutated CLL) or unmutated (Ig-unmutated CLL); and the presence or absence of mutations in this region of CLL cells distinguishes two clinically distinct forms. It is important for physicians to distinguish between patients with Ig-unmutated CLL, where typically have more indolent disease with median survivals close to 25 years, and Ig-mutated CLL, where have more aggressive disease with median survivals around eight years. In this work, a biosensor capable of diagnosis and distinguishing between these two types of CLL was reported. The biosensor was fabricated by modifying a gold electrode with gold nanoparticles (AuNPS) followed by coating of ZAP70 oligonucleotide probe on the surface to detect specific sequence of ZAP70 gene. ZAP70 could predict the IgVH mutation status and is a good marker for differentiating Ig-mutated and Ig-unmutated CLL and serve as prognostic marker. First, we focused on achieving hybridization between probe and its complementary sequence. Hybridization between probe and target was determined with electrochemical impedance spectroscopy (EIS). Then, our efforts turned to optimize the conditions for the detection of any point mutation and also to maximize the selectivity. Under optimal conditions, the biosensor has a good calibration range between 2.0 × 10(-14) and 1.0 × 10(-9)molL(-1), with ZAP70 DNA sequence detection limit of 4.0 × 10(-15)molL(-1). We successfully detect hybridization first in synthetic samples, and ultimately in blood samples from patients. Experimental results illustrated that the nanostructured biosensor clearly discriminates between mutated and non-mutated CLL and predict the IgVH mutation status, which it has been considered as the single most informative stage independent prognostic factor in CLL.

  4. Immunoglobulin and T Cell Receptor Genes: IMGT® and the Birth and Rise of Immunoinformatics

    PubMed Central

    Lefranc, Marie-Paule

    2014-01-01

    IMGT®, the international ImMunoGeneTics information system®1, (CNRS and Université Montpellier 2) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and proteins of the IgSF and MhSF superfamilies. IMGT® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences, and three-dimensional (3D) structures. The concepts include the IMGT® standardized keywords (concepts of identification), IMGT® standardized labels (concepts of description), IMGT® standardized nomenclature (concepts of classification), IMGT unique numbering, and IMGT Colliers de Perles (concepts of numerotation). IMGT® comprises seven databases, 15,000 pages of web resources, and 17 tools, and provides a high-quality and integrated system for the analysis of the genomic and expressed IG and TR repertoire of the adaptive immune responses. Tools and databases are used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma) and in antibody engineering and humanization. They include, for example IMGT/V-QUEST and IMGT/JunctionAnalysis for nucleotide sequence analysis and their high-throughput version IMGT/HighV-QUEST for next-generation sequencing (500,000 sequences per batch), IMGT/DomainGapAlign for amino acid sequence analysis of IG and TR variable and constant domains and of MH groove domains, IMGT/3Dstructure-DB for 3D structures, contact analysis and paratope/epitope interactions of IG/antigen and TR/peptide-MH complexes and IMGT/mAb-DB interface for therapeutic antibodies and fusion proteins for immune applications (FPIA). PMID:24600447

  5. The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins.

    PubMed

    Feige, Matthias J; Gräwert, Melissa A; Marcinowski, Moritz; Hennig, Janosch; Behnke, Julia; Ausländer, David; Herold, Eva M; Peschek, Jirka; Castro, Caitlin D; Flajnik, Martin; Hendershot, Linda M; Sattler, Michael; Groll, Michael; Buchner, Johannes

    2014-06-01

    Sharks and other cartilaginous fish are the phylogenetically oldest living organisms that rely on antibodies as part of their adaptive immune system. They produce the immunoglobulin new antigen receptor (IgNAR), a homodimeric heavy chain-only antibody, as a major part of their humoral adaptive immune response. Here, we report the atomic resolution structure of the IgNAR constant domains and a structural model of this heavy chain-only antibody. We find that despite low sequence conservation, the basic Ig fold of modern antibodies is already present in the evolutionary ancient shark IgNAR domains, highlighting key structural determinants of the ubiquitous Ig fold. In contrast, structural differences between human and shark antibody domains explain the high stability of several IgNAR domains and allowed us to engineer human antibodies for increased stability and secretion efficiency. We identified two constant domains, C1 and C3, that act as dimerization modules within IgNAR. Together with the individual domain structures and small-angle X-ray scattering, this allowed us to develop a structural model of the complete IgNAR molecule. Its constant region exhibits an elongated shape with flexibility and a characteristic kink in the middle. Despite the lack of a canonical hinge region, the variable domains are spaced appropriately wide for binding to multiple antigens. Thus, the shark IgNAR domains already display the well-known Ig fold, but apart from that, this heavy chain-only antibody employs unique ways for dimerization and positioning of functional modules.

  6. Estimating Copy Number and Allelic Variation at the Immunoglobulin Heavy Chain Locus Using Short Reads.

    PubMed

    Luo, Shishi; Yu, Jane A; Song, Yun S

    2016-09-01

    The study of genomic regions that contain gene copies and structural variation is a major challenge in modern genomics. Unlike variation involving single nucleotide changes, data on the variation of copy number is difficult to collect and few tools exist for analyzing the variation between individuals. The immunoglobulin heavy variable (IGHV) locus, which plays an integral role in the adaptive immune response, is an example of a complex genomic region that varies in gene copy number. Lack of standard methods to genotype this region prevents it from being included in association studies and is holding back the growing field of antibody repertoire analysis. Here we develop a method that takes short reads from high-throughput sequencing and outputs a genetic profile of the IGHV locus with the read coverage depth and a putative nucleotide sequence for each operationally defined gene cluster. Our operationally defined gene clusters aim to address a major challenge in studying the IGHV locus: the high sequence similarity between gene segments in different genomic locations. Tests on simulated data demonstrate that our approach can accurately determine the presence or absence of a gene cluster from reads as short as 70 bp. More detailed resolution on the copy number of gene clusters can be obtained from read coverage depth using longer reads (e.g., ≥ 100 bp). Detail at the nucleotide resolution of single copy genes (genes present in one copy per haplotype) can be determined with 250 bp reads. For IGHV genes with more than one copy, accurate nucleotide-resolution reconstruction is currently beyond the means of our approach. When applied to a family of European ancestry, our pipeline outputs genotypes that are consistent with the family pedigree, confirms existing multigene variants and suggests new copy number variants. This study paves the way for analyzing population-level patterns of variation in IGHV gene clusters in larger diverse datasets and for quantitatively

  7. Sensing the neuronal glycocalyx by glial sialic acid binding immunoglobulin-like lectins.

    PubMed

    Linnartz-Gerlach, B; Mathews, M; Neumann, H

    2014-09-01

    Sialic acid binding immunoglobulin-like lectins (Siglecs) are cell surface receptors of microglia and oligodendrocytes that recognize the sialic acid cap of healthy neurons and neighboring glial cells. Upon ligand binding, Siglecs typically signal through an immunoreceptor tyrosine-based inhibition motif (ITIM) to keep the cell in a homeostatic status and support healthy neighboring cells. Siglecs can be divided into two groups; the first, being conserved among different species. The conserved Siglec-4/myelin-associated glycoprotein is expressed on oligodendrocytes and Schwann cells. Siglec-4 protects neurons from acute toxicity via interaction with sialic acids bound to neuronal gangliosides. The second group of Siglecs, named CD33-related Siglecs, is almost exclusively expressed on immune cells and is highly variable among different species. Microglial expression of Siglec-11 is human lineage-specific and prevents neurotoxicity via interaction with α2.8-linked sialic acid oligomers exposed on the neuronal glycocalyx. Microglial Siglec-E is a mouse CD33-related Siglec member that prevents microglial phagocytosis and the associated oxidative burst. Mouse Siglec-E of microglia binds to α2.8- and α2.3-linked sialic acid residues of the healthy glycocalyx of neuronal and glial cells. Recently, polymorphisms of the human Siglec-3/CD33 were linked to late onset Alzheimer's disease by genome-wide association studies. Human Siglec-3 is expressed on microglia and produces inhibitory signaling that decreases uptake of particular molecules such as amyloid-β aggregates. Thus, glial ITIM-signaling Siglecs recognize the intact glycocalyx of neurons and are involved in the modulation of neuron-glia interaction in healthy and diseased brain.

  8. Estimating Copy Number and Allelic Variation at the Immunoglobulin Heavy Chain Locus Using Short Reads

    PubMed Central

    Luo, Shishi; Song, Yun S.

    2016-01-01

    The study of genomic regions that contain gene copies and structural variation is a major challenge in modern genomics. Unlike variation involving single nucleotide changes, data on the variation of copy number is difficult to collect and few tools exist for analyzing the variation between individuals. The immunoglobulin heavy variable (IGHV) locus, which plays an integral role in the adaptive immune response, is an example of a complex genomic region that varies in gene copy number. Lack of standard methods to genotype this region prevents it from being included in association studies and is holding back the growing field of antibody repertoire analysis. Here we develop a method that takes short reads from high-throughput sequencing and outputs a genetic profile of the IGHV locus with the read coverage depth and a putative nucleotide sequence for each operationally defined gene cluster. Our operationally defined gene clusters aim to address a major challenge in studying the IGHV locus: the high sequence similarity between gene segments in different genomic locations. Tests on simulated data demonstrate that our approach can accurately determine the presence or absence of a gene cluster from reads as short as 70 bp. More detailed resolution on the copy number of gene clusters can be obtained from read coverage depth using longer reads (e.g., ≥ 100 bp). Detail at the nucleotide resolution of single copy genes (genes present in one copy per haplotype) can be determined with 250 bp reads. For IGHV genes with more than one copy, accurate nucleotide-resolution reconstruction is currently beyond the means of our approach. When applied to a family of European ancestry, our pipeline outputs genotypes that are consistent with the family pedigree, confirms existing multigene variants and suggests new copy number variants. This study paves the way for analyzing population-level patterns of variation in IGHV gene clusters in larger diverse datasets and for quantitatively

  9. Antimicrobial activity of a novel hypervariable immunoglobulin domain-containing receptor Dscam in Cherax quadricarinatus.

    PubMed

    Li, Dan; Yu, Ai-Qing; Li, Xue-Jie; Zhu, You-Ting; Jin, Xing-Kun; Li, Wei-Wei; Wang, Qun

    2015-12-01

    Down syndrome cell adhesion molecule (Dscam) mediates innate immunity against pathogens in arthropods. Here, a novel Dscam from red claw crayfish Cherax quadricarinatus (CqDscam) was isolated. The CqDscam protein contains one signal peptide, ten immunoglobulin domains, six fibronectin type III domains, one transmembrane domain and cytoplasmic tail. CqDscam phylogenetically clustered with other invertebrate Dscams. Variable regions of CqDscam in N-terminal halves of Ig2 and Ig3 domains, complete Ig7 domain and TM domain can be reshuffled after transcription to produce a deluge of >37,620 potential alternative splice forms. CqDscam was detected in all tissues tested and abundantly expressed in immune system and nerve system. Upon lipopolysaccharides (LPS) and b-1, 3-glucans (Glu) challenged, the expression of CqDscam was up-regulated, while no response in expression occurred after injection with peptidoglycans (PG). Membrane-bound and secreted types of CqDscam were separated on the protein level, and were both extensively induced post LPS challenge. Membrane-bound CqDscam protein was not detected in the serum, but localized to the hemocyte surface by immuno-localization assay. In the antimicrobial assays, the recombinant LPS-induced isoform of CqDscam protein displayed bacterial binding and growth inhibitory activities, especially with Escherichia coli. These results suggested that CqDscam, as one of pattern-recognition receptors (PRRs), involved in innate immune recognition and defense mechanisms in C. quadricarinatus, possibly through alternative splicing. PMID:26497093

  10. The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma.

    PubMed

    Papanikolaou, X; Alapat, D; Rosenthal, A; Stein, C; Epstein, J; Owens, R; Yaccoby, S; Johnson, S; Bailey, C; Heuck, C; Tian, E; Joiner, A; van Rhee, F; Khan, R; Zangari, M; Jethava, Y; Waheed, S; Davies, F; Morgan, G; Barlogie, B

    2015-08-01

    As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ⩾65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein ⩾8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets. PMID:25753926

  11. The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma.

    PubMed

    Papanikolaou, X; Alapat, D; Rosenthal, A; Stein, C; Epstein, J; Owens, R; Yaccoby, S; Johnson, S; Bailey, C; Heuck, C; Tian, E; Joiner, A; van Rhee, F; Khan, R; Zangari, M; Jethava, Y; Waheed, S; Davies, F; Morgan, G; Barlogie, B

    2015-08-01

    As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ⩾65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein ⩾8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets.

  12. Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia.

    PubMed

    Teeling, J L; Jansen-Hendriks, T; Kuijpers, T W; de Haas, M; van de Winkel, J G; Hack, C E; Bleeker, W K

    2001-08-15

    The clinical benefit of intravenous immunoglobulin (IVIG) preparations in the treatment of immune thrombocytopenic purpura (ITP) is supposed to be mediated by blockade of Fc gamma receptor--bearing phagocytes. In 2 experimental models for ITP, it is shown that the therapeutic efficacy of IVIG preparations is related to the IgG dimer content present in these preparations. A rat monoclonal antibody (mAb; MWReg30) directed to the murine platelet-specific integrin alpha(IIb)beta(3) (gpIIb/IIIa) was administered intraperitoneally either as bolus injection or continuous infusion. With bolus injection, the circulating platelet count dropped to almost zero within 3 hours. Pretreatment with cobra venom factor did not affect platelet depletion, whereas pretreatment with anti-Fc gamma RII/III mAb 2.4G2 or IVIG greatly reduced platelet clearance. With continuous infusion, platelet numbers reached a steady state after 4 days, at approximately 25% of control. This reduction in platelets was, however, not observed in mice deficient for the FcR gamma-chain, lacking Fc gamma RI, Fc gamma RIII, and Fc gamma RIII(-/-) mice. Infusion of a single dose of IVIG with a high IgG dimer content on the 4th day--ie, mimicking therapeutic administration--resulted in a platelet increase for several days. IVIG predominantly consisting of monomeric IgG had no effect on platelet numbers. In conclusion, continuous infusion of MWReg30 induces thrombocytopenia in mice by enhancing Fc gamma receptor--mediated clearance of platelets. In this model, it is shown that IgG dimers present in IVIG preparations are responsible for the increase in platelet counts. (Blood. 2001;98:1095-1099)

  13. Jacalin interaction with human immunoglobulin A1 and bovine immunoglobulin G1: affinity constant determined by piezoelectric biosensoring.

    PubMed

    Pedroso, Mariele M; Pesquero, Naira C; Thomaz, Sandra M O; Roque-Barreira, Maria C; Faria, Ronaldo C; Bueno, Paulo R

    2012-03-01

    The affinity of the D-galactose-binding lectin from Artocarpus heterophyllus lectin, known as jacalin, with immonuglobulins (Igs) was determined by biofunctionalization of a piezoelectric transducer. This piezoelectric biofunctionalized transducer was used as a mass-sensitive analytical tool, allowing the real-time binding analysis of jacalin-human immunoglobulin A1 (IgA(1)) and jacalin-bovine IgG(1) interactions from which the apparent affinity constant was calculated. The strategy was centered in immobilizing jacalin on the gold electrode's surface of the piezoelectric crystal resonator using appropriate procedures based on self-assembling of 11-mercaptoundecanoic acid and 2-mercaptoethanol thiol's mixture, a particular immobilization strategy by which it was possible to avoid cross-interaction between the proteins over electrode's surface. The apparent affinity constants obtained between jacalin-human IgA(1) and jacalin-bovine IgG(1) differed by 1 order of magnitude [(8.0 ± 0.9) 10(5) vs (8.3 ± 0.1) 10(6) L mol(-1)]. On the other hand, the difference found between human IgA(1) and human IgA(2) interaction with jacalin, eight times higher for IgA(1), was attributed to the presence of O-linked glycans in the IgA(1) hinge region, which is absent in IgA(2). Specific interaction of jacalin with O-glycans, proved to be present in the human IgA(1) and hypothetically present in bovine IgG(1) structures, is discussed as responsible for the obtained affinity values.

  14. Amphibians have immunoglobulins similar to ancestral IgD and IgA from Amniotes.

    PubMed

    Estevez, Olivia; Garet, Elina; Olivieri, David; Gambón-Deza, Francisco

    2016-01-01

    We studied the immunoglobulin genes from either the genomes or RNAs of amphibians. In particular, we obtained data from one frog genome (Nanorana parkeri) and three transcriptomes of the Caudata order (Andrias davidianus, Notophthalmus viridescens and Cynops pyrrhogaster). Apart from the immunoglobulins IgM and IgY previously described, we identified several IgD related immunoglobulins. The species N. parkeri, N. viridescens and C. pyrrhogaster have two IgD genes, while Andrias davidianus has three such genes. The three Caudata species have long IgD immunoglobulins similar to IgD of reptiles, and could be an ancient relic from the common ancestor of IgD of all mammals and reptiles. We also found two IgA isotypes. The results suggest that one of the IgA may be the ancestor of IgA in crocodiles and birds, while the other could be the ancestor IgA found in mammals. These results provide information that could help understand the evolution of immunoglobulins in terrestrial vertebrates.

  15. Scintigraphic detection of bone and joint infections with indium-111-labeled nonspecific polyclonal human immunoglobulin G

    SciTech Connect

    Oyen, W.J.; Claessens, R.A.; van Horn, J.R.; van der Meer, J.W.; Corstens, F.H. )

    1990-04-01

    The utility of indium-111-({sup 111}In) labeled immunoglobulin G (IgG) to detect infection of bone and adjacent tissues was investigated. Proof of infection was obtained by cultures taken at surgery. All 32 patients showed focally increased uptake on the technetium-99m- (99mTc) methylene diphosphonate (MDP) skeletal scintigraphies. Labeled immunoglobulin correctly identified presence, location, extent and soft-tissue involvement of the suspected inflammatory site. In these patients, focally increasing accumulation was noted over 48 hr. Discrimination between infection and sterile inflammatory lesions was not possible. Two fractures, 6-mo-old, and an aseptic loosening of a total-hip prosthesis were not visualized. Side effects after the immunoglobulin administration were not observed. Radiolabeled immunoglobulin is a new and safe radiopharmaceutical for the investigation of infectious bone and joint disease. The sensitivity of this agent appears at least as high as that of labeled leukocytes. However, labeled immunoglobulin can easily be prepared in every nuclear medicine department.

  16. Immunoglobulin A nephropathy in horseshoe kidney: case reports and literature review.

    PubMed

    Hu, Panpan; Jin, Meiling; Xie, Yuansheng; Chen, Pu; Zhang, Xueguang; Yin, Zhong; Cai, Guangyan; Chen, Xiangmei

    2014-10-01

    Horseshoe kidney is the most common congenital renal fusion anomaly. Immunoglobulin A nephropathy is a common glomerulonephritis worldwide. However, the co-occurrence of these diseases had not been reported in the literature. We report the first two cases with the occurrence of immunoglobulin A nephropathy in horseshoe kidney. The first case was a 26-year-old male with hypertension and proteinuria (1.4 g/24 h), his pathological finding was primary immunoglobulin A nephropathy. The second case was a 15-year-old female who presented with recurrent peliosis on bilateral lower extremities, haematuria and proteinuria (1.7 g/24 h). Her renal biopsy finding was Henoch-Schonlein purpura nephritis (secondary immunoglobulin A nephropathy). In both cases, renal biopsy was performed by experienced doctors under ultrasonic guidance at the renal upper pole and no postoperative complications were observed. After they were treated based on the renal pathological findings for 6 months, urine protein excretion decreased significantly and blood pressure and serum creatinine stabilized. It is possible that immunoglobulin A nephropathy occurs in a horseshoe kidney patient. Renal biopsy may be valuable and viable for horseshoe kidney patients with heavy proteinuria to identify pathologic type of glomerulopathy and to guide treatment, if renal biopsy is performed by experienced doctors at the renal upper pole under renal ultrasonic guidance.

  17. A preliminary analysis of the immunoglobulin genes in the African elephant (Loxodonta africana).

    PubMed

    Guo, Yongchen; Bao, Yonghua; Wang, Hui; Hu, Xiaoxiang; Zhao, Zhihui; Li, Ning; Zhao, Yaofeng

    2011-02-25

    The genomic organization of the IgH (Immunoglobulin heavy chain), Igκ (Immunoglobulin kappa chain), and Igλ (Immunoglobulin lambda chain) loci in the African elephant (Loxodonta africana) was annotated using available genome data. The elephant IgH locus on scaffold 57 spans over 2,974 kb, and consists of at least 112 V(H) gene segments, 87 D(H) gene segments (the largest number in mammals examined so far), six J(H) gene segments, a single μ, a δ remnant, and eight γ genes (α and ε genes are missing, most likely due to sequence gaps). The Igκ locus, found on three scaffolds (202, 50 and 86), contains a total of 153 V(κ) gene segments, three J(κ) segments, and a single C(κ) gene. Two different transcriptional orientations were determined for these V(κ) gene segments. In contrast, the Igλ locus on scaffold 68 includes 15 V(λ) gene segments, all with the same transcriptional polarity as the downstream J(λ)-C(λ) cluster. These data suggest that the elephant immunoglobulin gene repertoire is highly diverse and complex. Our results provide insights into the immunoglobulin genes in a placental mammal that is evolutionarily distant from humans, mice, and domestic animals.

  18. Transient hypogammaglobulinemia and severe atopic dermatitis: Open-label treatment with immunoglobulin in a case series

    PubMed Central

    Lin, Joanna H.; Roberts, Robert; Lim, Kellie J.; Stiehm, E. Richard

    2016-01-01

    Background: We reported on six infants between 5 and 11 months old, with transient hypogammaglobulinemia of infancy and severe refractory atopic dermatitis, who were treated with open-label immunoglobulin (Ig) after conventional therapy failed. All six infants had an IgG level of <225 mg/dL, elevated eosinophil and IgE levels, and no urine or stool protein losses, but they did exhibit hypoalbuminemia. Objective: To evaluate the utility of open-label immunoglobulin in infants with severe atopic dermatitis for whom conventional therapy failed. We reviewed the clinical utility of intravenous immunoglobulin in the treatment of severe atopic dermatitis, the most recent research in the field, and suggested mechanisms for its benefit. Methods: The six infants were identified from a retrospective chart review at the University of California Los Angeles Allergy and Immunology outpatient pediatric clinic. Results: All six patients were treated with 400 mg/kg/month of intravenous immunoglobulin and had normalization of their IgG and albumin levels, and all but one had clinically improved atopic dermatitis. Conclusion: Infants with severe atopic dermatitis who did not respond to conventional therapy avoidance may benefit from intravenous immunoglobulin therapy. PMID:27470901

  19. [Intravenous immunoglobulin (IVIG) as treatment for recurrent pregnancy loss (RPL)].

    PubMed

    Sapir, Tal; Carp, Howard; Shoenfeld, Yehuda

    2005-06-01

    Miscarriages are the most common complication in human pregnancies. Recurrent pregnancy loss (RPL) could occur for several reasons, such as: immunological abnormalities of the pregnant women and chromosomal abnormalities of the embryo. There are several autoimmune characteristics for RPL, such as autoantibodies, and sometimes RPL are a symptom of an autoimmune disease. It is unclear whether the autoantibodies are the cause, the consequence or an artifact of the RPL. Intravenous immunoglobulin (IVIG) is a preparation made of purified plasma of thousands of healthy donors. Currently, IVIG is provided as a treatment for several autoimmune diseases. There are reports on a beneficial effect of IVIG for women with RPL of unknown reason. Some reports indicate a beneficial effect of IVIG independent of aspirin, as well as in artificial fertilization. Nevertheless, the efficacy of IVIG has yet to be established. Perhaps a certain sub-group should be defined of women who suffer from RPL and have greater odds for successful IVIG treatment. A sub-group analysis showed that, in secondary RPL, IVIG is more successful when provided after embryo implantation, whereas, in primary RPL, IVIG is better when provided prior to conceiving. Apart from the miscarriage type (secondary or primary) other factors that might influence the IVIG-treatment success were found: the number of previous miscarriages, the age of the pregnant women and the way IVIG is administrated. The mechanisms of action of IVIG in RPL are multiple, complex and not fully understood. IVIG therapy regulates the immune system in several mechanisms, in a way that might increase the survival rate of the embryo in the uterus and might decrease the odds of a miscarriage. For example, one of the main mechanisms of IVIG in RPL is down-regulation of natural killer cells (NK cells) activity and expression. This finding is of great importance because it has been reported that women who have never given birth and have high levels

  20. Comparison and Characterization of Immunoglobulin G Subclasses among Primate Species

    PubMed Central

    Shearer, Michael H.; Dark, Robyn D.; Chodosh, James; Kennedy, Ronald C.

    1999-01-01

    Little information is available on the immunoglobulin G (IgG) subclasses expressed in the sera of nonhuman primate species. To address this issue, we compared the IgG subclasses found in humans (IgG1, IgG2, IgG3, and IgG4) to those of nonhuman primates, such as baboons and macaques. Cross-reactive antihuman IgG subtype-specific reagents were identified and used to analyze purified IgG from sera by solid-phase enzyme-linked immunosorbent assay. Protein A-purified human IgG obtained from sera was composed of IgG1, IgG2, IgG3, and IgG4, whereas baboon and macaque IgG was composed of IgG1, IgG2, and IgG4. Protein G-purified human IgG was composed of IgG1, IgG2, IgG3, and IgG4, whereas baboon and macaque IgG was composed of IgG1, IgG2, and IgG4. To test the possibility that baboon and macaque IgG3 is actually present, but is outcompeted for binding to proteins A and G by the other more abundant IgG subclasses, we repurified the IgG from sera that did not bind either protein A or protein G. We found a baboon IgG3 population in the sera that did not bind protein A, but bound protein G. No IgG3 subtype was detectable in macaque sera. These data suggest that baboon sera, like human sera, contain four IgG subtypes, whereas macaque sera exhibit only three of the human subclass analogs. In addition, the IgG subtype-specific reagents were shown to be useful in determining the IgG subclass distribution following vaccination of baboons with hepatitis B surface antigen. PMID:10548592

  1. A second immunoglobulin light chain isotype in the rainbow trout.

    PubMed

    Partula, S; Schwager, J; Timmusk, S; Pilström, L; Charlemagne, J

    1996-01-01

    A novel immunoglobulin (Ig) light chain isotype, termed IgL2, has been isolated from trout lymphoid tissues both by reverse transcription - polymerase chain reaction (PCR) and screening of cDNA libraries. The CL domain of the new isotype shares only 29% residues with a recently cloned trout IgL isotype, termed IgL1, which has some similarities to Ckappa and Clambda isotype domains of several vertebrate species. Using anchored PCR, a VL element rearranged to CL2 was isolated. It is a member of a new VL family (VL2) of which four members were sequenced. These differ in the sequence of CDR1 and CDR2 but are remarkably similar in CDR3, i. e., at the junction between VL and JL segments. VL elements are rearranged to novel JL elements which differ from those described for VL1-CL1 rearrangements. Two cDNA clones contained JL-CL2 segments but no VL segments. The JL segments were preceded by typical rearrangements signal sequences [RSS, nonamer-23 base pair (bp) spacer-heptamer]. Further upstream of RSS were located two to three near identical 53 bp repeats, each of which included a 16 bp sequence similar to KI and KII sequences located at similar places in human and mouse Jk1 genes. These sequences are believed to act as binding sites for the protein KLP, which could be a transcriptional factor involved in the synthesis of germline Jk transcripts. Their phylogenic conservation in vertebrates suggests that they have an important role in B-cell differentiation. Remarkably, an RNA species of about 0.7 kilobase is the predominant IgL mRNA in trout spleen and coincides in size with JLCL2 transcripts. Genomic DNA blot analysis indicates that the trout L2 locus has a cluster-like organization similar to the trout L1 locus and the IgL locus of several teleost fish. A phylogenic analysis of VL2 and CL2 corroborates their low similarity to other vertebrate IgL chains and suggests an ancient diversification of the IgL locus. PMID:8881036

  2. Fc receptors for immunoglobulins and their appearance during vertebrate evolution.

    PubMed

    Akula, Srinivas; Mohammadamin, Sayran; Hellman, Lars

    2014-01-01

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR. PMID:24816777

  3. Enzyme-linked immunosorbent assay for measuring ileal symbiont intracellularis-specific immunoglobulin G response in sera of pigs.

    PubMed Central

    Holyoake, P K; Cutler, R S; Caple, I W; Monckton, R P

    1994-01-01

    Proliferative enteritis (PE) is a common intestinal disease on pig farms. The disease is caused by ileal symbiont (IS) intracellularis (Campylobacter-like organisms) bacteria. An enzyme-linked immunosorbent assay (ELISA) was developed to measure IS intracellularis-specific immunoglobulin G (IgG) response in the sera of pigs. The antigen used in the ELISA was filtered, percoll gradient-purified IS intracellularis extracted from the intestines of pigs affected with proliferative hemorrhagic enteropathy. The antibody responses of pigs challenged with intestinal homogenates from pigs affected with proliferative hemorrhagic enteropathy containing IS intracellularis or percoll-gradient purified IS intracellularis were low and variable. The low IgG titers measured in challenged pigs support previous findings that IgG plays a minor role in the immune response of pigs to IS intracellularis. On a farm in which infection was endemic, pigs seroconverted at between 7 and 24 weeks of age. High IgG titers, indicative of maternally acquired antibody, were present in 3-week-old pigs. The IgG titers in piglets were lowest at 6 weeks of age, which approximates the age of onset of clinical disease. These results suggest that IgG plays a role in determining the susceptibilities of pigs to natural infection. Measurements of seroconversion by the ELISA might aid in epidemiological investigations of PE in naturally infected herds. However, the variable antibody responses in experimentally challenged pigs would seem to limit its usefulness as an antemortem diagnostic test for PE. PMID:7989553

  4. Structural Characterization of the Partially Folded Intermediates of An Immunoglobulin Light Chain Leading to Amyloid Fibrillation And Amorphous Aggregation

    SciTech Connect

    Qin, Z.; Hu, D.; Zhu, M.; Fink, A.L.; /UC, Santa Cruz

    2007-07-12

    Immunoglobulin light chain deposition diseases involve various types of extracellular deposition of light chain variable domains, including amyloid fibrils and amorphous deposits. The decreased thermodynamic stability of the light chain is believed to be the major factor leading to fibrillation. However, the differences in the nature of the deposits among the light chain deposition diseases raise the question of whether the mechanisms leading to fibrillar or amorphous aggregation is different. In this study, we generated two partially folded intermediates of the light chain variable domain SMA in the presence of guanidine hydrochloride (GuHCl) and characterized their conformations. The more unfolded intermediate formed fibrils most rapidly, while the more native-like intermediate predominantly led to amorphous deposits. The results also show that the monomeric, rather than the dimeric state, was critical for fibrillation. The data also indicate that fibril elongation involves addition of a partially unfolded intermediate, rather than the native state. We postulate that a more highly unfolded intermediate is more suited to undergo the topological rearrangements necessary to form amyloid fibrils than a more structured one and that this also correlates with increased destabilization. In the case of light chain aggregation, it appears that more native-like intermediate conformations are more prone to form amorphous deposits.

  5. Clinical usefulness of oral immunoglobulins in lung transplant recipients with norovirus gastroenteritis: a case series.

    PubMed

    Gairard-Dory, A-C; Dégot, T; Hirschi, S; Schuller, A; Leclercq, A; Renaud-Picard, B; Gourieux, B; Kessler, R

    2014-12-01

    Viral gastroenteritis causing diarrhea is a common complication observed in lung transplant recipients. Differently from the mild and typically self-limited disease seen in immunocompetent subjects, immunocompromised patients frequently have a more severe course. Norovirus and rotavirus are among the leading causes of severe gastroenteritis in transplant recipients. Specific treatment is unavailable, although good supportive treatment can significantly reduce morbidity. Previous studies have suggested that oral immunoglobulins may be used for the treatment of acute viral gastroenteritis after solid-organ transplantation. Herein, we conducted a retrospective chart review of 12 lung transplant recipients with norovirus-induced gastroenteritis who were treated with oral immunoglobulins for 2 days. Eleven patients were successfully treated, whereas 1 subject was only mildly improved. Four patients had at least 1 recurrence. No significant adverse effects were observed. We conclude that oral immunoglobulins may be clinically useful for lung transplant recipients with norovirus-induced gastroenteritis.

  6. Segmental myofiber necrosis in myotonic dystrophy - An immunoperoxidase study of immunoglobulins in skeletal muscle.

    PubMed Central

    Silver, M. M.; Banerjee, D.; Hudson, A. J.

    1983-01-01

    Because serum immunoglobulin G levels are low in patients with myotonic dystrophy, it was hypothesized that it might be catabolized within abnormal muscle fibers. Accordingly, immunohistochemical stains for immunoglobulins were performed on muscle sections derived at biopsy or autopsy from patients with myotonic dystrophy, other forms of muscular dystrophy, nondystrophic muscle disease, or normal muscle. Positive staining for immunoglobulins was found only in necrotic segments of myofibers (in 7 of 19 dystrophic and 6 of 27 nondystrophic subjects), and it is believed that the staining was due to nonspecific diffusion. However, staining reactions distinguished between incipient necrosis and artifactual contraction bands and allowed us to study segmental myofiber necrosis, comparing its frequency in the various muscle diseases. Segmental myofiber necrosis was present in 4 of 16 cases of myotonic dystrophy. The relevance of this finding to the clinical and morphologic features of myotonic dystrophy is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:6351629

  7. The use of immunoglobulin light chain assays in the diagnosis of paraprotein-related kidney disease

    PubMed Central

    Yadav, Punit; Leung, Nelson; Sanders, Paul W.; Cockwell, Paul

    2016-01-01

    Kidney involvement is common in paraprotein-related diseases. A diversity of clinical presentations and histopathological features can occur secondary to tissue injury caused by precipitation or deposition of a clonal immunoglobulin, usually an immunoglobulin light chain. The paraprotein is either produced by multiple myeloma or by a clone of B-cell lineage that does not fulfill diagnostic criteria for multiple myeloma. The recent introduction of serum immunoglobulin free light chain assays, which accurately quantify both light chain isotypes to produce a ratio that indicates the presence or absence of a light chain paraprotein, is a major clinical development. However, as the interpretation of the assay can be challenging, the aim of this review is to clarify the role of serum and urinary light chain assays in the screening and diagnosis of paraprotein-related kidney disease. PMID:25296094

  8. Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta)

    NASA Technical Reports Server (NTRS)

    Stone, W. H.; Saphire, D. G.; Hackleman, S. M.; Braun, A. M.; Pennington, P.; Scheffler, J.; Wigle, J. C.; Cox, A. B.

    1994-01-01

    We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure to protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age.

  9. [Is intravenous immunoglobulin effective in toxic epidermal necrolysis and Stevens-Johnson syndrome?].

    PubMed

    Navajas, Lucas; Rada, Gabriel

    2014-10-17

    Toxic epidermal necrolysis and Stevens-Johnson syndrome are severe cutaneous adverse drug reactions. Intravenous immunoglobulin is described as a therapeutic option, however its use is still controversial. Using Epistemonikos database, which is maintained by screening over 20 databases, we identified six systematic reviews, including 39 primary studies. We combined the evidence using tables for summary of findings, following the GRADE approach, and concluded there is uncertainty about the effects of intravenous immunoglobulin because the certainty of the evidence is very low; it probably leads to important adverse effects; and has high cost. Intravenous immunoglobulin should not be used outside the context of a clinical trial, or only in cases where other treatments have failed and there are no resource constraints.

  10. Methylation patterns of immunoglobulin genes in lymphoid cells: correlation of expression and differentiation with undermethylation.

    PubMed

    Storb, U; Arp, B

    1983-11-01

    Different states of eukaryotic gene expression are often correlated with different levels of methylation of DNA sequences containing structural genes and their flanking regions. To assess the potential role of DNA methylation in the expression of immunoglobulin genes, which require complex rearrangements prior to expression, methylation patterns were examined in cell lines representing different stages of lymphocyte maturation. Methylation of the second cytosine in the sequence 5' C-C-G-G 3' was determined by using Hpa II/Msp I endonuclease digestion. Four CH genes (C mu, C delta, C gamma 2b, and C alpha), C kappa, V kappa, C lambda, and V lambda genes were analyzed. The results lead to the following conclusions: (i) transcribed immunoglobulin genes are undermethylated; (ii) the C gene allelic to an expressed C gene is always also undermethylated; and (iii) all immunoglobulin loci tend to become increasingly undermethylated as B cells mature.

  11. Quarter variation and correlations of colostrum albumin, immunoglobulin G1 and G2 in dairy cows.

    PubMed

    Samarütel, Jaak; Baumrucker, Craig R; Gross, Josef J; Dechow, Chad D; Bruckmaier, Rupert M

    2016-05-01

    A high variation in immunoglobulin G1 (IgG1) concentration in first milked quarter colostrum has been reported, but BSA quarter colostrum variation is not known. The occurrence of serum albumin in milk has been attributed to increased blood-milk barrier penetration. Reports of serum albumin binding to the Fc Receptor of the neonate, the receptor thought to be responsible for IgG1 transcytosis, suggested that a correlation with the appearance of IgG1 in colostrum of dairy cows was likely. The objective of the study was to establish the quarter colostrum concentration and mass of immunoglobulins and serum albumin. First colostrum was quarter collected within 4 h of parturition from healthy udders of 31 multiparous dairy cows. Individual quarter colostrum weight was determined and a sample of each was frozen for subsequent analysis. Concentrations of immunoglobulin G1, G2, and BSA were measured by ELISA and total mass of components was calculated. In addition, colostrum was also analysed for L-lactate dehydrogenase activity. Analysis of concentration and mass of BSA, immunoglobulin G1, G2 established that the quarter variations were different by cow, quarter and quarter within cow. Partial correlations corrected for colostrum weight indicated that BSA and IgG2 concentration and mass are closely correlated while that of BSA and IgG1 concentration and mass exhibited no correlation suggesting that BSA and IgG1 may have different transport mechanisms. Interestingly, immunoglobulin G1 and G2 concentration and mass exhibited strong correlations suggesting that also some unknown mechanism of immunoglobulin G2 appearance in colostrum is occurring. Finally, no measured protein exhibited any correlation with the activity of lactate dehydrogenase in colostrum.

  12. Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire.

    PubMed

    Glanville, Jacob; Zhai, Wenwu; Berka, Jan; Telman, Dilduz; Huerta, Gabriella; Mehta, Gautam R; Ni, Irene; Mei, Li; Sundar, Purnima D; Day, Giles M R; Cox, David; Rajpal, Arvind; Pons, Jaume

    2009-12-01

    Antibody repertoire diversity, potentially as high as 10(11) unique molecules in a single individual, confounds characterization by conventional sequence analyses. In this study, we present a general method for assessing human antibody sequence diversity displayed on phage using massively parallel pyrosequencing, a novel application of Kabat column-labeled profile Hidden Markov Models, and translated complementarity determining region (CDR) capture-recapture analysis. Pyrosequencing of domain amplicon and RCA PCR products generated 1.5 x 10(6) reads, including more than 1.9 x 10(5) high quality, full-length sequences of antibody variable fragment (Fv) variable domains. Novel methods for germline and CDR classification and fine characterization of sequence diversity in the 6 CDRs are presented. Diverse germline contributions to the repertoire with random heavy and light chain pairing are observed. All germline families were found to be represented in 1.7 x 10(4) sequences obtained from repeated panning of the library. While the most variable CDR (CDR-H3) presents significant length and sequence variability, we find a substantial contribution to total diversity from somatically mutated germline encoded CDRs 1 and 2. Using a capture-recapture method, the total diversity of the antibody library obtained from a human donor Immunoglobulin M (IgM) pool was determined to be at least 3.5 x 10(10). The results provide insights into the role of IgM diversification, display library construction, and productive germline usages in antibody libraries and the humoral repertoire. PMID:19875695

  13. Ig Constant Region Effects on Variable Region Structure and Function

    PubMed Central

    Janda, Alena; Bowen, Anthony; Greenspan, Neil S.; Casadevall, Arturo

    2016-01-01

    The adaptive humoral immune response is responsible for the generation of antimicrobial proteins known as immunoglobulin molecules or antibodies. Immunoglobulins provide a defense system against pathogenic microbes and toxins by targeting them for removal and/or destruction. Historically, antibodies have been thought to be composed of distinct structural domains known as the variable and constant regions that are responsible for antigen binding and mediating effector functions such as opsonization and complement activation, respectively. These domains were thought to be structurally and functionally independent. Recent work has revealed however, that in some families of antibodies, the two regions can influence each other. We will discuss the body of work that led to these observations, as well as the mechanisms that have been proposed to explain how these two different antibody regions may interact in the function of antigen binding. PMID:26870003

  14. [The effect of blood serum polyreactive immunoglobulins on serum antibody affinity determination].

    PubMed

    Bobrovnik, S A; Demchenko, M A; Komisarenko, S V

    2010-01-01

    The presence of polyreactive immunoglobulins in sera may substantially influence on the accuracy of antibody affinity determination. In order to obtain precise values of antibody affinity one should apply one of two following ways. First, one should block polyreactive immunoglobulins with high concentration of Twin 20 and high concentration of any antigen which does not interact with studying antibody. After this antibody affinity may be determined by traditional methods. Another way is the application of the method suggested by us earlier, which allow determining affinity of two antibodies in a mixture and the relation of their concentrations.

  15. Effects of Ovarian Steroids on Immunoglobulin-Secreting Cell Function in Healthy Women

    PubMed Central

    Lü, Fabien X.; Ma, Zhongmin; Moser, Susie; Evans, Thomas G.; Miller, Christopher J.

    2003-01-01

    To determine the effect of the ovarian hormone cycle on immunity, immunoglobulin-secreting cell (ISC) frequency and lymphocyte subsets were examined in the blood of healthy women. We found that immunoglobulin A (IgA)-secreting cells (IgA-ISC) were fourfold more frequent than IgG-ISC in peripheral blood mononuclear cells (PBMC). Further, the ISC frequency in PBMC was highest (P < 0.05) during the periovulatory stage of the menstrual cycle. Thus, endogenous ovarian steroids regulate the ISC frequency and this may explain why women are more resistant to viral infections and tend to have more immune-mediated diseases than men do. PMID:12965931

  16. Glomerular disease with idiopathic linear immunoglobulin deposition: a rose by any other name would be atypical.

    PubMed

    Rosales, Ivy A; Colvin, Robert B

    2016-04-01

    Nasr et al. (2016) report 20 cases of "atypical anti-GBM disease," characterized by bright, linear glomerular basement membrane (GBM) immunoglobulin deposition in patients who lacked anti-GBM antibodies by conventional testing and who had a relatively benign course. Half had light chain restriction. The term "idiopathic linear immunoglobulin deposition" may be preferable until anti-GBM activity is demonstrable, since there are alternative mechanisms of linear deposition in the GBM, including physicochemical affinity for GBM components and alterations of the GBM itself.

  17. Functional Role of Carbohydrate Residues in Human Immunoglobulin G and Therapeutic Monoclonal Antibodies.

    PubMed

    Dorokhov, Y L; Sheshukova, E V; Kosobokova, E N; Shindyapina, A V; Kosorukov, V S; Komarova, T V

    2016-08-01

    Therapeutic monoclonal antibodies (TMA) provide an important means for treating diseases that were previously considered untreatable. Currently more than 40 full-size TMAs created primarily based on immunoglobulin G1 are widely used for treating various illnesses. Glycosylation of TMA is among other numerous factors that affect their biological activity, effector functions, immunogenicity, and half-life in the patient's serum. The importance of carbohydrate residues for activity of human serum immunoglobulin and TMA produced in animal cells is considered in this review, with emphasis given to N-glycosylation of the Fc fragment of the antibody. PMID:27677552

  18. Estimation of serum, salivary immunoglobulin G, immunoglobulin A levels and total protein, hemoglobin in smokeless tobacco chewers and oral submucous fibrosis patients

    PubMed Central

    Balakrishnan, Chandrakanth; Aswath, Nalini

    2015-01-01

    Background: Oral submucous fibrosis (OSMF) is a debilitating, potentially cancerous oral condition. Although areca nut is the most important causative agent, it is also considered that the disease is immunologically mediated. Aim of the Study: To establish that autoimmunity and nutritional deficiency play a role in the etiopathogenesis of OSMF. Objectives of the Study: To show that serum immunoglobulin markers (immunoglobulin-G [IgG], immunoglobulin-A [IgA]) and nutritional parameters such as total serum protein (TSP), Hemoglobin (Hb) play a role in causing OSMF and also to correlate serum, salivary IgG, IgA levels in OSMF patients. Settings and Design: A case-control study was done with 50 patients (25 patients who were provisionally diagnosed as OSMF - Group I, and 25 patients who were chronic smokeless tobacco chewers and who did not have any intraoral lesion - Group II). Materials and Methods: Five milliliters of blood and saliva were collected from both the groups. Quantitative analysis of serum, and salivary IgG, IgA was done by turbidometric immunoassay. TSP and Hemoglobin (Hb) were estimated by spectrophotometry. Statistical Analysis: Results were analyzed by independent samples t-test and one-way analysis of variance (ANOVA). Results: All patients of OSMF showed significant (P < 0.01) increase in serum IgG, IgA, and salivary IgG levels as compared to smokeless tobacco chewers. The salivary IgA levels showed a significant decrease in OSMF patients (P < 0.05). TSP and Hb levels showed significant (P < 0.01) decrease in OSMF patients as compared to smokeless tobacco chewers. Conclusion: The elevation of immunoglobulin levels supports the concept of autoimmunity. The decrease in TSP and Hb suggests that nutritional deficiency plays a defined role in the occurrence as well as a further progression of OSMF. PMID:26604567

  19. Calculating the Dose of Subcutaneous Immunoglobulin for Primary Immunodeficiency Disease in Patients Switched From Intravenous to Subcutaneous Immunoglobulin Without the Use of a Dose-Adjustment Coefficient

    PubMed Central

    Fadeyi, Michael; Tran, Tin

    2013-01-01

    Primary immunodeficiency disease (PIDD) is an inherited disorder characterized by an inadequate immune system. The most common type of PIDD is antibody deficiency. Patients with this disorder lack the ability to make functional immunoglobulin G (IgG) and require lifelong IgG replacement therapy to prevent serious bacterial infections. The current standard therapy for PIDD is intravenous immunoglobulin (IVIG) infusions, but IVIG might not be appropriate for all patients. For this reason, subcutaneous immunoglobulin (SCIG) has emerged as an alternative to IVIG. A concern for physicians is the precise SCIG dose that should be prescribed, because there are pharmacokinetic differences between IVIG and SCIG. Manufacturers of SCIG 10% and 20% liquid (immune globulin subcutaneous [human]) recommend a dose-adjustment coefficient (DAC). Both strengths are currently approved by the FDA. This DAC is to be used when patients are switched from IVIG to SCIG. In this article, we propose another dosing method that uses a higher ratio of IVIG to SCIG and an incremental adjustment based on clinical status, body weight, and the presence of concurrent diseases. PMID:24391400

  20. An inherited immunoglobulin class-switch recombination deficiency associated with a defect in the INO80 chromatin remodeling complex

    PubMed Central

    Kracker, Sven; Di Virgilio, Michela; Schwartzentruber, Jeremy; Cuenin, Cyrille; Forveille, Monique; Deau, Marie-Céline; McBride, Kevin M.; Majewski, Jacek; Gazumyan, Anna; Seneviratne, Suranjith; Grimbacher, Bodo; Kutukculer, Necil; Herceg, Zdenko; Cavazzana, Marina; Jabado, Nada; Nussenzweig, Michel C.; Fischer, Alain; Durandy, Anne

    2015-01-01

    Background Immunoglobulin class-switch recombination defects (CSR-D) are rare primary immunodeficiencies characterized by impaired production of switched immunoglobulin isotypes and normal or elevated IgM levels. They are caused by impaired T:B cooperation or intrinsic B cell defects. However, many immunoglobulin CSR-Ds are still undefined at the molecular level. Objective This study's objective was to delineate new causes of immunoglobulin CSR-Ds and thus gain further insights into the process of immunoglobulin class-switch recombination (CSR). Methods Exome sequencing in 2 immunoglobulin CSR-D patients identified variations in the INO80 gene. Functional experiments were performed to assess the function of INO80 on immunoglobulin CSR. Results We identified recessive, nonsynonymous coding variations in the INO80 gene in 2 patients affected by defective immunoglobulin CSR. Expression of wild-type INO80 in patients' fibroblastic cells corrected their hypersensitivity to high doses of γ-irradiation. In murine CH12-F3 cells, the INO80 complex accumulates at Sα and Eμ regions of the IgH locus, and downregulation of INO80 as well as its partners Reptin and Pontin impaired CSR. In addition, Reptin and Pontin were shown to interact with activation-induced cytidine deaminase. Finally, an abnormal separation of sister chromatids was observed upon INO80 downregulation in CH12-F3 cells, pinpointing its role in cohesin activity. Conclusion INO80 deficiency appears to be associated with defective immunoglobulin CSR. We propose that the INO80 complex modulates cohesin function that may be required during immunoglobulin switch region synapsis. PMID:25312759

  1. Controlling variability.

    PubMed

    Sanger, Terence D

    2010-11-01

    In human motor control, there is uncertainty in both estimation of initial sensory state and prediction of the outcome of motor commands. With practice, increasing precision can often be achieved, but such precision incurs costs in time, effort, and neural resources. Therefore, motor planning must account for variability, uncertainty, and noise, not just at the endpoint of movement but throughout the movement. The author presents a mathematical basis for understanding the time course of uncertainty during movement. He shows that it is possible to achieve accurate control of the endpoint of a movement even with highly inaccurate and variable controllers. The results provide a first step toward a theory of optimal control for variable, uncertain, and noisy systems that must nevertheless accomplish real-world tasks reliably.

  2. The breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis.

    PubMed

    Baer, R; Heppell, A; Taylor, A M; Rabbitts, P H; Boullier, B; Rabbitts, T H

    1987-12-01

    T-cell tumors are characterized by inversions or translocations of chromosome 14. The breakpoints of these karyotypic abnormalities occur in chromosome bands 14q11 and 14q32--the same bands in which the T-cell receptor (TCR) alpha-chain and immunoglobulin heavy chain genes have been mapped, respectively. Patients with ataxia-telangiectasia are particularly prone to development of T-cell chronic lymphocytic leukemia with such chromosomal abnormalities. We now describe DNA rearrangements of the TCR alpha-chain gene in an ataxia-telangiectasia-associated leukemia containing both a normal and an inverted chromosome 14. The normal chromosome 14 has undergone a productive join of TCR alpha-chain variable (V alpha) and joining (J alpha) gene segments. The other allele of the TCR alpha-chain gene features a DNA rearrangement, about 50 kilobases from the TCR alpha-chain constant (C alpha) gene, that represents the breakpoint of the chromosome 14 inversion; this breakpoint is comprised of a TCR J alpha segment (from 14q11) fused to sequences derived from 14q32 but on the centromeric side of C mu. These results imply that 14q32 sequences located at an undetermined distance downstream of the immunoglobulin C mu locus can contribute to the development of T-cell tumors.

  3. Biochemical parameters in the blood of Holstein calves given immunoglobulin Y-supplemented colostrums

    PubMed Central

    2014-01-01

    Background In any calf rearing system it is desirable to obtain healthy animals, and reduce morbidity, mortality, and economic losses. Bovine syndesmochorial placentation prevents the direct transfer of bovine immunoglobulins to the fetus, and calves are born hypogammaglobulinemic. These calves therefore require colostrum immediately after birth. Colostrum is rich in immunoglobulins (Ig) and its consumption results in the transfer of passive immunity to calves. The Ig absorption occurs within the first 12 h after birth. Immunoglobulin Y (IgY), derived from chicken egg yolk, has been used in the prevention and control of diseases affecting calves because it is very similar in structure and function to immunoglobulin G (IgG). In the current study, we sought to establish whether administration routes of colostrum supplemented with avian IgY affected passive immunity in calves. Results No significant differences were observed with respect to route of administration for colostrum. However, we did observe some differences in certain interactions between the various treatments. Calves fed colostrum containing egg yolk had higher levels of TP, ALB, and IgG, along with increased GGT activity. Conclusions Our results suggest that supplementing colostrum with egg yolk has a beneficial effect when given to calves, regardless of administration route. PMID:25022282

  4. High-level production of a functional immunoglobulin heterodimer in a baculovirus expression system.

    PubMed Central

    Hasemann, C A; Capra, J D

    1990-01-01

    A murine immunoglobulin heterodimer has been expressed in a baculovirus expression system. This was achieved by using both double infection of insect cells with separate heavy- and light-chain-expressing viruses and infection with a double-recombinant virus containing both the immunoglobulin heavy- and light-chain cDNAs. In both cases, the polypeptide chains were correctly processed, glycosylated, and assembled into normal H2L2 (H = heavy, L = light) immunoglobulin monomers. These molecules bound antigen and expressed both polyclonal idiotype and monoclonal idiotopes. Furthermore, the transfer vectors described have been modified to contain the F1 origin of replication for the production of single-stranded DNA, which facilitates site-specific mutations of either the polyhedrin promoter or the inserted foreign gene. Use of this system should significantly advance the analysis of the structural bases for both idiotype expression and antigen binding by immunoglobulin. More importantly, it provides a generic method for the high-level expression of antibodies of diverse interest. Images PMID:2111022

  5. Intravenous Immunoglobulin with Enhanced Polyspecificity Improves Survival in Experimental Sepsis and Aseptic Systemic Inflammatory Response Syndromes

    PubMed Central

    Djoumerska-Alexieva, Iglika; Roumenina, Lubka; Pashov, Anastas; Dimitrov, Jordan; Hadzhieva, Maya; Lindig, Sandro; Voynova, Elisaveta; Dimitrova, Petya; Ivanovska, Nina; Bockmeyer, Clemens; Stefanova, Zvetanka; Fitting, Catherine; Bläss, Markus; Claus, Ralf; von Gunten, Stephan; Kaveri, Srini; Cavaillon, Jean-Marc; Bauer, Michael; Vassilev, Tchavdar

    2015-01-01

    Sepsis is a major cause for death worldwide. Numerous interventional trials with agents neutralizing single proinflammatory mediators have failed to improve survival in sepsis and aseptic systemic inflammatory response syndromes. This failure could be explained by the widespread gene expression dysregulation known as “genomic storm” in these patients. A multifunctional polyspecific therapeutic agent might be needed to thwart the effects of this storm. Licensed pooled intravenous immunoglobulin preparations seemed to be a promising candidate, but they have also failed in their present form to prevent sepsis-related death. We report here the protective effect of a single dose of intravenous immunoglobulin preparations with additionally enhanced polyspecificity in three models of sepsis and aseptic systemic inflammation. The modification of the pooled immunoglobulin G molecules by exposure to ferrous ions resulted in their newly acquired ability to bind some proinflammatory molecules, complement components and endogenous “danger” signals. The improved survival in endotoxemia was associated with serum levels of proinflammatory cytokines, diminished complement consumption and normalization of the coagulation time. We suggest that intravenous immunoglobulin preparations with additionally enhanced polyspecificity have a clinical potential in sepsis and related systemic inflammatory syndromes. PMID:26701312

  6. Reversible and irreversible cross-linking of immunoglobulin heavy chains through their carbohydrate residues.

    PubMed Central

    Heimgartner, U; Kozulić, B; Mosbach, K

    1990-01-01

    After periodate oxidation and incubation with a dihydrazide, cross-linking of the two heavy chains of immunoglobulins G from several species proceeds specifically through their oligosaccharides. We have used malonic acid dihydrazide, adipic acid dihydrazide and dithiodipropionic acid dihydrazide. The last compound is introduced in this work as a cleavable-carbohydrate-specific cross-linker. It was found that in rabbit and human immunoglobulins the degree of cross-linking was strongly dependent on the oxidation conditions but only very weakly dependent on the concentration and size of the dihydrazides. Papain cleavage of the cross-linked rabbit IgG indicated that the cross-linking occurred predominantly, if not exclusively, in the Fc region, probably through the two glycans linked to Asn-297 in the CH2 domain of each of the two heavy chains. The immunoglobulins from sheep, pig, goat and guinea pig show a comparable cross-linking pattern, indicating that the sugar chains from these immunoglobulins have a spatial structure closely related to that of rabbit and human IgG. When dithiodipropionic acid dihydrazide was used as the cross-linker, the cross-link could be cleaved by mercaptoethanol. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:2111130

  7. Brief Report: Immunoglobulin A Deficiency in a Subset of Autistic Subjects.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1997-01-01

    A study of 40 individuals (ages 5-31) with autism investigated immune deficiency. Results found the subjects had significantly lower serum immunoglobulin A (IgA) levels than that of age- and sex-matched controls. Seventeen subjects had one of three haplotypes associated with IgA deficiency and seven of these had decreased IgA levels. (CR)

  8. Raised immunoglobulin concentrations in bronchoalveolar lavage fluid of healthy granite workers.

    PubMed

    Calhoun, W J; Christman, J W; Ershler, W B; Graham, W G; Davis, G S

    1986-04-01

    Immunoglobulin concentrations and lymphocyte counts were determined in bronchoalveolar fluid obtained from nine symptomless, healthy, non-smoking granite workers (mean age 45.6, range 22-56 years) and nine normal, non-smoking, non industrial controls (mean age 22.8, range 21-32 years). The proteins were measured in unconcentrated lavage fluid by means of a solid phase, enzyme linked immunosorbent assay. IgG and IgA concentrations were three times greater in lavage fluid from granite workers than the samples from non-industrial controls (p less than 0.02). Eight of nine normal volunteers (89%) had no detectable IgM (less than 30 ng/ml) in the lavage fluid whereas eight of nine (89%) granite workers had detectable IgM (chi 2 = 8, p less than 0.01). Lymphocyte counts in lavage fluid from the workers were significantly greater (15.5%) than control counts (5.6%; p less than 0.05). The normal albumin concentration suggests that differences in permeability do not account for all of the increased immunoglobulin concentrations found in granite workers' lavage fluid and that some immunoglobulin is locally synthesised. It is concluded that occupational exposure to granite dust is associated with an increased proportion of lymphocytes and an increased concentration of immunoglobulin in lavage fluid that may reflect a subclinical immune inflammatory response.

  9. The determination of the rate of conjugation immunoglobuline with bifunctional chelator

    NASA Astrophysics Data System (ADS)

    Málek, Z.; Miler, V.; Budský, F.

    2006-01-01

    The work was performed under the GACR project: "Technology of preparation of radionuclides and their labelled compounds for nuclear medicine and pharmacy with the use of the reactor LVR-15" reg. no. 104/03/0499. Imaging of cell’s antigens with the use of labelled immunoglobulines allows imaging of specific receptors on cell membrane and specific tumours. It is necessary to carry out the labelling of the immunoglobulines with radionuclides of suitable physical properties, which form cations (e.g., 111In, 90Y, 177Lu) that form very strong chelates of sufficiently high stability constant preventing the dissociation of complexes or the radionuclide under “in-vivo” conditions. The immunoglobuline must be conjugated with the bifunctional chelator (BCH), which contains both chelating unit and reactive group for binding to the immunoglobuline. In our laboratory we have conjugated human IgG and monoclonal antibody CD20 with diethylenetriamine pentaacetic acid dianhydride (cDTPAA). Radionuclides 90Y and 177Lu prepared on the LVR-15 reactor in NRI Rez were used for labelling. After conjugation and labelling the yields in relation to the amount of isotopic carrier have been determined.

  10. Teaching the Structure of Immunoglobulins by Molecular Visualization and SDS-PAGE Analysis

    ERIC Educational Resources Information Center

    Rižner, Tea Lanišnik

    2014-01-01

    This laboratory class combines molecular visualization and laboratory experimentation to teach the structure of the immunoglobulins (Ig). In the first part of the class, the three-dimensional structures of the human IgG and IgM molecules available through the RCSB PDB database are visualized using freely available software. In the second part, IgG…

  11. Transfection of an immunoglobulin kappa gene into mature human B lymphocytes

    SciTech Connect

    Bich-Thuy, L.T.; Queen, C.

    1988-01-01

    The authors show in this report that the transcription induced by interleukin-2 or pokeweed mitogens of the kappa MOPC 41 immunoglobulin light-chain gene transfected into primary human or murine B lymphocytes initiates from a previously unobserved start site about 26 base pairs upstream of the start site used in myeloma cell lines.

  12. No evidence of asymptomatic variant CJD infection in immunodeficiency patients treated with UK-sourced immunoglobulin.

    PubMed

    Helbert, M R; Bangs, C; Bishop, M; Molesworth, A; Ironside, J

    2016-04-01

    Surveillance of 75 immunodeficiency patients exposed to UK-sourced immunoglobulin, including batches derived from donors who went on to develop vCJD, has not detected any clinical cases of vCJD, or of asymptomatic infection in 15 patients with available tissue samples of sufficient quality for testing. PMID:26529032

  13. Immunoperoxidase staining of surface and intracellular immunoglobulin in human neoplastic lymphoid cells.

    PubMed Central

    Mason, D Y; Leonard, R C; Laurent, G; Gourdin, M F

    1980-01-01

    An immunoperoxidase technique for the optical microscopic detection of cellular immunoglobulin has been used to stain fixed smears of human neoplastic B lymphoid cells. Only four out of 28 cases of chronic lymphatic leukaemia (CLL) showed membrane labelling by this technique. In contrast, when 14 samples from other types of B lymphoproliferative disorder (including hairy cell leukaemia, non-Hodgkin's lymphoma, and prolymphocytic leukaemia) were studied, all samples showed membrane immunoglobulin labelling (confirmed by capping experiments). This discrepancy was attributed to the greater density of surface immunoglobulin present on neoplastic cells in the latter group of disorders compared to CLL. This immunoperoxidase technique is therefore less sensitive than immunofluorescent staining of cells in suspension for the demonstration of neoplastic cell surface immunoglobulin. However, it offers a number of advantages (eg, excellent visualisation of cell morphology, permanence of stained preparations, and applicability to stored samples) which recommend it as the method of choice in certain clinical haematological contexts. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:7000833

  14. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptom.

    PubMed

    Kon, Tetsuo; Nakagawa, Naoki; Yoshikawa, Fumitsugu; Haba, Kazunao; Kitagawa, Nagako; Izumi, Michihiro; Kumazaki, Setsuo; Ishida, Satoshi; Aikawa, Ryuichi

    2016-08-01

    Immunoglobulin light-chain (AL) amyloidosis is characterized by the deposition of insoluble fibrils composed of immunoglobulin light chains secreted by monoclonal plasma cells. Given the recent advances in the therapy of AL amyloidosis, it is important to diagnose this disease as early as possible. Herein, we describe the case of a 62-year-old man with hepatitis C virus (HCV)-related cirrhosis presenting with hematochezia. Colonoscopy showed multiple submucosal hematomas within the region ranging from the transverse colon to the sigmoid colon. Kappa immunoglobulin light-chain amyloid deposition was also detected. Bone marrow examination revealed a monoclonal abnormal plasma cell population. Thus, the patient was diagnosed with systemic immunoglobulin light-chain amyloidosis. The hematochezia was conservatively managed. However, because of liver failure caused by liver cirrhosis, the patient developed massive pleural effusion and died of respiratory failure. Postmortem examination revealed amyloid deposition in the esophagus, stomach, duodenum, ileum, descending colon, pancreas, heart, and lung. In these organs, amyloid deposition was limited to the vascular wall. We concluded that AL amyloidosis can present hematochezia arising from submucosal hematoma in the large colon before other systemic symptoms appear.

  15. Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies

    PubMed Central

    Beauté, J; Levy, P; Millet, V; Debré, M; Dudoit, Y; Le Mignot, L; Tajahmady, A; Thomas, C; Suarez, F; Pellier, I; Hermine, O; Aladjidi, N; Mahlaoui, N; Fischer, A

    2010-01-01

    Lifelong immunoglobulin replacement is the standard, expensive therapy for severe primary antibody deficiencies. This treatment can be administrated either by intravenous immunoglobulin (IVIG) or subcutaneous infusions (SCIG) and delivered at home or in an out-patient setting. This study aims to determine whether SCIG is cost-effective compared with IVIG from a French social insurance perspective. Because both methods of administration provide similar efficacies, a cost-minimization analysis was performed. First, costs were calculated through a simulation testing different hypothesis on costs drivers. Secondly, costs were estimated on the basis of field data collected by a questionnaire completed by a population of patients suffering from agammaglobulinaemia and hyper-immunoglobulin (Ig)M syndrome. Patients' satisfaction was also documented. Results of the simulation showed that direct medical costs ranged from €19 484 for home-based IVIG to €25 583 for hospital-based IVIG, with home-based SCIG in between at €24 952 per year. Estimations made from field data were found to be different, with significantly higher costs for IVIG. This result was explained mainly by a higher immunoglobulin mean dose prescribed for IVIG. While the theoretical model showed very little difference between SCIG and hospital-based IVIG costs, SCIG appears to be 25% less expensive with field data because of lower doses used in SCIG patients. The reality of the dose difference between both routes of administration needs to be confirmed by further and more specific studies. PMID:20041884

  16. [The protective activity of 2 normal immunoglobulin preparations for intravenous administration in experimental Pseudomonas aeruginosa infection].

    PubMed

    Vasilev, Ch L; Veleva, K V; Tekelieva, R Kh; Pencheva, P I

    1991-02-01

    The antibody levels in 18 batches of the preparations of human immunoglobulin, Immunovenin and Immunovenin-Intact, for intravenous injection were determined in the enzyme immunoassay with the use of the mixture of P. aeruginosa lipopolysaccharide antigens of seven immunotypes. The average antibody titers in these preparations were identical. The preparations were found to have protective action against P. aeruginosa experimental infection in mice.

  17. Systemic immunoglobulin light-chain amyloidosis presenting hematochezia as the initial symptom.

    PubMed

    Kon, Tetsuo; Nakagawa, Naoki; Yoshikawa, Fumitsugu; Haba, Kazunao; Kitagawa, Nagako; Izumi, Michihiro; Kumazaki, Setsuo; Ishida, Satoshi; Aikawa, Ryuichi

    2016-08-01

    Immunoglobulin light-chain (AL) amyloidosis is characterized by the deposition of insoluble fibrils composed of immunoglobulin light chains secreted by monoclonal plasma cells. Given the recent advances in the therapy of AL amyloidosis, it is important to diagnose this disease as early as possible. Herein, we describe the case of a 62-year-old man with hepatitis C virus (HCV)-related cirrhosis presenting with hematochezia. Colonoscopy showed multiple submucosal hematomas within the region ranging from the transverse colon to the sigmoid colon. Kappa immunoglobulin light-chain amyloid deposition was also detected. Bone marrow examination revealed a monoclonal abnormal plasma cell population. Thus, the patient was diagnosed with systemic immunoglobulin light-chain amyloidosis. The hematochezia was conservatively managed. However, because of liver failure caused by liver cirrhosis, the patient developed massive pleural effusion and died of respiratory failure. Postmortem examination revealed amyloid deposition in the esophagus, stomach, duodenum, ileum, descending colon, pancreas, heart, and lung. In these organs, amyloid deposition was limited to the vascular wall. We concluded that AL amyloidosis can present hematochezia arising from submucosal hematoma in the large colon before other systemic symptoms appear. PMID:27318996

  18. Dysphagia secondary to dermatomyositis treated successfully with intravenous immunoglobulin: a case report

    PubMed Central

    Joshi, Deepak; Mahmood, Rizwan; Williams, Peter; Kitchen, Paul

    2008-01-01

    A 46 year old woman presented with a one month history of rash and mylagia. The history, clinical findings and blood tests all supported a diagnosis of dermatomyositis. The patient later developed dysphagia and was successfully treated with intravenous immunoglobulin. Investigations and treatment of dysphagia in the context of dermatomyositis are discussed. PMID:18651969

  19. Analysis of rearranged immunoglobulin genes indicating a process of clonal evolution in chronic lymphocytic leukaemia.

    PubMed

    Hakim, I; Rechavi, G; Brok-Simoni, F; Grossman, Z; Amariglio, N; Mandel, M; Ramot, B; Ben-Bassat, I; Katzir, N

    1993-07-01

    Chronic lymphocytic leukaemia (CLL) is known to be a stable monoclonal neoplasm. In contrast to early studies demonstrating no more than two hybridizing immunoglobulin heavy chain bands corresponding to the two expected alleles, we have demonstrated an unexpected multiband pattern when the HindIII-digested DNA samples from 38 CLL patients were analysed by Southern blot hybridization using JH and C mu gene probes. In order to characterize the genetic basis for the multiband pattern, we molecularly cloned the immunoglobulin heavy chain genes of one of the patients whose leukaemic DNA sample demonstrated three hybridizing JH bands and a loss of the germline band. The cloned rearranged immunoglobulin genes could be divided, based on the restriction mapping and the hybridization with the various probes, into two basic patterns representing two alleles. In one of the cloned rearranged immunoglobulin genes a secondary rearrangement occurred that resulted in the addition of 300 base-pair long sequence into the switch region, and the creation of a HindIII restriction site. The results of the study suggest that clonal evolution occurs in some CLL, and that many of these neoplasms are indeed oligoclonal due to the accumulation of secondary genetic changes.

  20. Comparison of five commercial anti-tetanus toxoid immunoglobulin G enzyme-linked immunosorbent assays.

    PubMed

    Perry, A L; Hayes, A J; Cox, H A; Alcock, F; Parker, A R

    2009-12-01

    Five commercially available enzyme-linked immunosorbent assays for the measurement of anti-tetanus toxoid immunoglobulin G (IgG) antibodies were evaluated for performance. The data suggest that there are manufacturer-dependent differences in sensitivity and accuracy for the determination of tetanus toxoid IgG antibodies that could result in different diagnostic interpretations.

  1. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Immunoglobulin G (Fc fragment specific) immunological test system. 866.5530 Section 866.5530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... abnormalities, e.g., gamma heavy chain disease. (b) Classification. Class I (general controls). The device...

  2. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulin G (Fc fragment specific) immunological test system. 866.5530 Section 866.5530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... abnormalities, e.g., gamma heavy chain disease. (b) Classification. Class I (general controls). The device...

  3. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Immunoglobulin G (Fc fragment specific) immunological test system. 866.5530 Section 866.5530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... abnormalities, e.g., gamma heavy chain disease. (b) Classification. Class I (general controls). The device...

  4. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Immunoglobulin G (Fc fragment specific) immunological test system. 866.5530 Section 866.5530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... abnormalities, e.g., gamma heavy chain disease. (b) Classification. Class I (general controls). The device...

  5. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... test system. 866.5510 Section 866.5510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a)...

  6. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) immunological test system. 866.5520 Section 866.5520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system....

  7. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... test system. 866.5510 Section 866.5510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a)...

  8. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) immunological test system. 866.5520 Section 866.5520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5520 Immunoglobulin G (Fab fragment specific) immunological test system....

  9. Immunoglobulin E antibodies against a reactive dye--a case report.

    PubMed

    Hagmar, L; Welinder, H; Dahlquist, I

    1986-06-01

    The presence of specific IgE (immunoglobulin E) antibodies against a conjugate between human serum albumin and a reactive azo dye (Levafix Goldgelb E-3GA, Reactive Orange 67) was demonstrated by the radioallergosorbent test (RAST), RAST inhibition, and skin prick tests in an occupationally exposed subject with symptoms of mainly rhinoconjunctivitis.

  10. Which variability?

    PubMed

    Toraldo, Alessio; Luzzatti, Claudio

    2006-02-01

    Drai and Grodzinsky provide a valuable analysis that offers a way of disentangling the effects of Movement and Mood in agrammatic comprehension. However, their mathematical implementation (Beta model) hides theoretically relevant information, i.e., qualitative heterogeneities of performance within the patient sample. This heterogeneity is crucial in the variability debate.

  11. The role of CTCF binding sites in the 3' immunoglobulin heavy chain regulatory region.

    PubMed

    Birshtein, Barbara K

    2012-01-01

    The immunoglobulin heavy chain locus undergoes a series of DNA rearrangements and modifications to achieve the construction and expression of individual antibody heavy chain genes in B cells. These events affect variable regions, through VDJ joining and subsequent somatic hypermutation, and constant regions through class switch recombination (CSR). Levels of IgH expression are also regulated during B cell development, resulting in high levels of secreted antibodies from fully differentiated plasma cells. Regulation of these events has been attributed primarily to two cis-elements that work from long distances on their target sequences, i.e., an ∼1 kb intronic enhancer, Eμ, located between the V region segments and the most 5' constant region gene, Cμ; and an ∼40 kb 3' regulatory region (3' RR) that is located downstream of the most 3' C(H) gene, Cα. The 3' RR is a candidate for an "end" of B cell-specific regulation of the Igh locus. The 3' RR contains several B cell-specific enhancers associated with DNase I hypersensitive sites (hs1-4), which are essential for CSR and for high levels of IgH expression in plasma cells. Downstream of this enhancer-containing region is a region of high-density CTCF binding sites, which extends through hs5, 6, and 7 and further downstream. CTCF, with its enhancer-blocking activities, has been associated with all mammalian insulators and implicated in multiple chromosomal interactions. Here we address the 3' RR CTCF-binding region as a potential insulator of the Igh locus, an independent regulatory element and a predicted modulator of the activity of 3' RR enhancers. Using chromosome conformation capture technology, chromatin immunoprecipitation, and genetic approaches, we have found that the 3' RR with its CTCF-binding region interacts with target sequences in the V(H), Eμ, and C(H) regions through DNA looping as regulated by protein binding. This region impacts on B cell-specific Igh processes at different stages of B cell

  12. The physiological effects of human immunoglobulin on severe bronchiolitis patients before and after treatment.

    PubMed

    Shan, Yan-Hua; Zhang, Yong-Gang; Zhang, Jian-Hua; Wang, Dong; Li, Xiao-Xia; Zhang, Jie; Wang, Xi-Mei; Luo, Song-Yuan

    2015-01-01

    The goal of the present study is to explore the physiological effects of injected human immunoglobulin on patients with severe bronchiolitis before and after treatment. 86 young children with severe bronchiolitis were randomly divided into the observation group (43 cases) and the treatment group (43 cases). On the basis of conventional therapy, the children in the treatment group were given human immunoglobulin (400 mg/kg, 1-3 times) via intravenous injection. 60 healthy young children, as determined by a physical examination given at the Zhumadian Central Hospital, were enrolled as the control group. The T lymphocytes, cytokines, IgA, IgG, and IgM immunoglobulins in the peripheral blood of all 3 groups were measured. The clinical efficacy of the immunoglobulins to mitigate the effects of bronchiolitis and the amount of time for the reduction of symptoms to occur were observed. The serum Ca, Fe, and Zn levels of children with severe bronchiolitis were significantly lower than those of the healthy control group (p < 0.05). As such, the CD8, IgA, IgG, IgM and IFN-γ levels were also significantly lower in the children with severe bronchiolitis than in the children in the healthy control group (p < 0.05). Furthermore, the CD4, IgE, IL-4, and IL-4/IFN-γ levels and CD4/CD8 ratio were dramatically higher than in the healthy control group (p < 0.05). Serum levels of the aforementioned indicators either increased or decreased after IVIG treatment. The amount of time required for coughing, wheezing, and pulmonary rales to seize, and the duration of illness for the children with the severe bronchiolitis children was significantly shorter for those in the treatment group than for those in the observation group. Human immunoglobulin via intravenous injection showed active therapeutical effects on trace elements, T lymphocytes, and cytokines in patients with severe bronchiolitis.

  13. Antiglycolipid antibodies, immunoglobulins and paraproteins in motor neuron disease: a population based case-control study.

    PubMed

    Willison, H J; Chancellor, A M; Paterson, G; Veitch, J; Singh, S; Whitelaw, J; Kennedy, P G; Warlow, C P

    1993-02-01

    The role of humoral autoimmune factors in the pathogenesis of motor neuron disease (MND) is currently under considerable scrutiny. In particular, there have been many reports of abnormal serum immunoglobulin patterns and elevated titres of anti-ganglioside antibodies in patients with MND. However, many of these studies may be biased by the selection criteria for patients and controls. In order to carefully address this issue we obtained 82 blood samples from consecutive MND patients identified through a national MND register in combination with 82 community controls matched for age, sex and geographical area. We used these samples to determine the frequency of monoclonal immunoglobulins (mIgs) and measure the levels of serum immunoglobulins and anti-GM1 ganglioside antibodies in sporadic cases of MND in comparison with normal controls. Serum mIgs detected using high resolution and immunofixation agarose electrophoresis were present in 1.2% of MND patients and 2.4% of controls. Using a highly sensitive isoelectric focusing and immunoblotting method, monoclonal or oligoclonal immunoglobulins were found in 28% of MND patients and 27% of controls. Anti-GM1 antibodies were present in 26% of MND patients and 18% of controls (odds ratio = 1.5, 95%, CI 0.7-3.6) with no significant differences in titres between the 2 groups. Mean immunoglobulin G, A and M levels were equal in 2 groups. Thus, although alterations in these parameters were identified, we were unable to demonstrate any significant difference between MND patients and controls. We conclude that the majority of sporadic cases of MND are unlikely to have an autoimmune basis as judged by the lack of abnormalities in these parameters.

  14. Phylogenetic origins of antibody structure. II. Immunoglobulins in the primary immune response of the bullfrog, Rana catesbiana.

    PubMed

    Marchalonis, J; Edelman, G M

    1966-11-01

    The anuran amphibian, Rana catesbiana, has been found to possess at least two kinds of immunoglobulins corresponding to gammaG- and gammaM-classes. These classes have the same chain structures as those of their counterparts in higher animal species. Light chains of both immunoglobulins had molecular weights of 20,000. Heavy chains of the gammaM-class had molecular weights of 72,100; those of the gammaG-class had molecular weights of 53,600. The carbohydrate content of the gammaG-immunoglobulin was 2.1%, and that of the gammaM-protein was 10.8%. The amino acid compositions of the immunoglobulins were generally similar to those of mammalian immunoglobulins. After a single injection of phage antigen (f2), the order of appearance of phage-neutralizing activity in the frog immunoglobulin classes was (a) gammaM-antibodies, and (b) gammaG-antibodies. The results of this and previous studies suggest that the gammaG-immunoglobulins emerged at some point in evolution between the elasmobranchs and the anuran amphibians. PMID:4162734

  15. Immunoblot analysis of serum immunoglobulin G response to surface proteins of Clostridium difficile in patients with antibiotic-associated diarrhea.

    PubMed Central

    Pantosti, A; Cerquetti, M; Viti, F; Ortisi, G; Mastrantonio, P

    1989-01-01

    We examined by immunoblot analysis the serum immunoglobulin G antibody response to EDTA-extracted surface proteins of Clostridium difficile in 16 patients with antibiotic-associated diarrhea. For each patient, paired serum samples were tested against proteins of the infecting strain and of a collection strain (C253) known to belong to the electrophoretic group 2 pattern. Eight patients, all harboring group 2 C. difficile strains, exhibited responses to the proteins of the infecting strain; six patients showed increases in the level of antibodies between acute-phase and convalescent-phase sera. A great variability in the antigens recognized was found; however, seven patients possessed antibodies directed against an antigen of about 35 kilodaltons, corresponding to the major protein of group 2 strains. The sera of these seven patients cross-reacted also with the 35-kilodalton and other proteins of strain C253. Our data show that C. difficile proteins other than toxins can elicit an immune response in patients with C. difficile-associated disease; in this group of patients, the major surface protein of the group 2 strains was the antigen most often recognized. Images PMID:2808681

  16. p21 is dispensable for AID-mediated class switch recombination and mutagenesis of immunoglobulin genes during somatic hypermutation.

    PubMed

    Shansab, Maryam; Selsing, Erik

    2011-03-01

    In B cells, activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM) at rearranged immunoglobulin (Ig) variable (V) regions. Previous studies have shown that both monoubiquitination of proliferating cell nuclear antigen (PCNA) and translesional DNA polymerase activity are important for inducing mutagenesis during SHM. Regulation of PCNA ubiquitination by p21, also known as Cdkn1a and p21(Cip1/Waf1), is an important mechanism that controls mutation loads in mammalian cells. In this study, we have assessed whether p21 has an in vivo function in regulating mutagenesis in B cells by analyzing SHM frequency in p21-deficient mice. Our results show that p21 is dispensable for SHM. This suggests that, during SHM of Ig genes, p21 does not act to regulate mutagenesis load. We also show that p21 transcript levels are the same in both wildtype and AID-deficient B cells during B cell activation, and that AID-mediated class switch recombination (CSR) is not affected by p21 deficiency; thereby indicating that p21 regulation in B cells is not altered by AID-induced DNA damage and that p21 has no affect on AID-dependent Ig gene diversification. Our results suggest that regulation of p21 in activated B cells is probably more important for maintaining proper cell cycle progression as opposed to promoting SHM of Ig genes.

  17. Development of human-murine chimeric immunoglobulin G for use in the serological detection of human flavivirus and alphavirus antibodies.

    PubMed

    Thibodeaux, Brett A; Panella, Amanda N; Roehrig, John T

    2010-10-01

    Diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the indirect IgG ELISA. Broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, West Nile, yellow fever, Japanese encephalitis, Saint Louis encephalitis, and Powassan viruses), or alphaviruses (e.g., Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis, and chikungunya viruses) that can cause human disease. We have created human-murine chimeric monoclonal antibodies (cMAbs) by combining the variable regions of flavivirus (6B6C-1) or alphavirus (1A4B-6) broadly cross-reactive murine MAbs (mMAbs) with the constant region of human IgG1. These cMAbs may be used as standardized reagents capable of replacing human infection-immune-positive control sera in indirect IgG ELISA for diagnosis of all human flaviviral or alphaviral infections. The IgG cMAbs secreted from plasmid-transformed Sp2/0-Ag14 cells had serological activity identical to that of the parent mMAbs, as measured by ELISA using multiple flaviviruses or alphaviruses.

  18. Interaction of Artocarpus lectins with human IgA does not involve asparagine-linked oligosaccharide of the immunoglobulin.

    PubMed

    Hashim, O H; Kobayashi, K; Taniguchi, N

    1992-07-01

    In view of the controversy with respect to the interaction of jacalin with human IgA2, a study was undertaken to assess the reactivity of the Artocarpus heterophyllus lectin, as well as the lectin from Artocarpus integer (lectin C), with subclasses of human immunoglobulin A by ELISA. Our data is consistent with the view that Artocarpus lectins have no affinity for the IgA2 immunoglobulins. In further support of the findings, we have established that N-linked oligosaccharide moieties of IgA have no significant bearing in the lectin-immunoglobulin binding. Interaction was also not affected in the presence of 1% (w/v) BSA.

  19. [Analyses of the rearrangement of T-cell receptor- and immunoglobulin genes in the diagnosis of lymphoproliferative disorders].

    PubMed

    Griesser, D H

    1995-01-01

    Rearrangements are developmentally regulated genetic recombinations in T and B cells which generate functional T cell receptor (TcR) and immunoglobulin genes, respectively. Different variable, sometimes diversity, and joining gene segments which are discontinuously spread out within their chromosomal location in germline configuration, are randomly assembled in individual lymphocytes. These rearrangements can be detected by Southern Blot analysis if more than 5% of a total lymphocyte population in a biopsy specimen carries the same clonal rearrangement. We analyzed DNA from 324 snap-frozen biopsy specimens from lympho-proliferative disorders. None of the 20 reactive lesions and four malignant myelomonocytic tumors had a clonal antigen receptor gene rearrangement. All 117 malignant B cell lymphomas of different subtypes and 95 of 97 malignant T cell lymphomas showed a clonal gene rearrangement. Only two angioimmunoblastic lymphadenopathy(AILD)-type T cell lymphomas did not have immune receptor gene rearrangements. They were morphologically indistinguishable from the other 47 T/AILD lymphomas with clonal rearrangement patterns. In most cases TcR beta and immunoglobulin heavy chain (IgH) gene probes were sufficient for lineage assignment of the clonal T or B lymphocyte population. In 18% of B lymphomas, however, a cross-lineage rearrangement of TcR beta genes, and in 20% of the T cell lymphomas a clonal IgH gene rearrangement was detected. After exclusion of centrocytic, large cell anaplastic lymphomas (LCAL) of B-type, and T/AILD lymphomas which are overrepresented in our study, only 10% of the remaining 147 T and B cell lymphomas had aberrant rearrangements. TcR rearrangements other than those of the beta chain genes were extremely rare in B cell lymphomas, as were Ig kappa rearrangements in T lymphomas. Only two T/AILD lymphomas had IgH and Ig kappa rearrangement in addition to their clonal T cell receptor gene rearrangements. Both samples likely contain a clonal B

  20. Comparison of serum free light chain and urine electrophoresis for the detection of the light chain component of monoclonal immunoglobulins in light chain and intact immunoglobulin multiple myeloma.

    PubMed

    Dejoie, Thomas; Attal, Michel; Moreau, Philippe; Harousseau, Jean-Luc; Avet-Loiseau, Herve

    2016-03-01

    Response criteria for multiple myeloma are based upon changes in monoclonal protein levels quantified using serum and/or urine protein electrophoresis. The latter lacks sensitivity at low monoclonal protein levels and since 2001, the serum free light chain test has been available and its clinical utility proven, yet guidelines have not recommended it as a replacement for urine assessment. Herein we evaluated responses using serum free light chain measurements and serum and urine electrophoresis after 2 and 4 cycles of therapy and after stem cell transplantation in 25 light chain and 157 intact immunoglobulin myeloma patients enrolled in the IFM 2007-02 MM trial. All 25 light chain patients had measurable disease by serum free light chain and urine methods at presentation. By contrast 98 out of 157 intact immunoglobulin patients had measurable disease by serum free light chain compared to 55 out of 157 by urine electrophoresis. In all patients there was substantial agreement between predicate (serum/urine protein electrophoresis) and test (serum protein electrophoresis and serum free light chain) methods for response assessment (Weighted Kappa=0.83). Urine immunofixation became negative in 47% light chain and 43% intact immunoglobulin patients after 2 cycles of therapy. At this time the serum free light chain ratio normalised in only 11% and 27% patients, respectively. In summary we found good agreement between methods for response assessment, but the serum free light chain test provided greater sensitivity than urine electrophoresis for monitoring. To our knowledge this is the first report comparing both methods for response assignment based on the International Myeloma Working Group guidelines. (Clinical Trials Register.eu identifier: 2007-005204-40).

  1. Laser-based microdissection of single cells from tissue sections and PCR analysis of rearranged immunoglobulin genes from isolated normal and malignant human B cells.

    PubMed

    Küppers, Ralf; Schneider, Markus; Hansmann, Martin-Leo

    2013-01-01

    Normal and malignant B cells carry rearranged immunoglobulin (Ig) variable region genes, which due to their practically limitless diversity represent ideal clonal markers for these cells. We describe here an approach to isolate single cells from frozen tissue sections by microdissection using a laser-based method. From the isolated cells rearranged IgH and Igκ genes are amplified in a semi-nested PCR approach, using a collection of V gene family-specific primers recognizing nearly all V gene segments together with primers for the J gene segments. By sequence analysis of V genes from distinct cells, the clonal relationship of the B lineage cells can unequivocally be determined and related to the histological distribution of the cells. The approach is also useful to determine V, D, and J gene usage. Moreover, the presence and pattern of somatic Ig V gene mutations give valuable insight into the stage of differentiation of the B cells.

  2. Association between common variable immunodeficiency and collagenous infiltrative disorders of the gastrointestinal tract: A series of four patients.

    PubMed

    Mandaliya, Rohan; Burkart, Ashlie L; DiMarino, Anthony J; Rattan, Satish; Cohen, Sidney

    2016-03-01

    Hypogammaglobulinemia/common variable immunodeficiency (CVID) may lead to disruption of the gut mucosal immune barrier. Collagenous infiltrative disorders of the intestinal tract (colitis, gastritis, sprue) constitute a relatively new spectrum of gastrointestinal disorders. Our aims were (1) to determine the association between immunoglobulin deficiency state like CVID and collagenous infiltrative disorders of the gut and (2) to study the clinic-pathologic characteristics and treatment outcomes in these patients. A retrospective search was conducted to identify cases with concurrence of these two conditions at an academic center from 2007 to 2013. Four such patients were identified from our database: three with collagenous colitis and one with collagenous gastritis. All patients with collagenous colitis had normal colonic mucosa while the patient with collagenous gastritis had nodular gastric mucosa. Only one patient out of four had decreased plasma cells in the submucosa as expected in low immunoglobulin states. All patients had improvement in their symptoms on immunoglobulin therapy with considerable remission on budesonide. Literature search revealed reporting of four similar patients. In conclusion, (1) the association between collagenous infiltrative disorders of the gut and CVID and its prompt response to immunoglobulins with effective maintenance with budesonide are novel findings. Our study also shows that the presence of plasma cells should not rule out the possibility of CVID. (2) In patients with chronic diarrhea, hypogammaglobulinemia and collagenous colitis/sprue should be considered for the available effective treatments such as immunoglobulins and budesonide. PMID:27053352

  3. Marsupial and monotreme serum immunoglobulin binding by proteins A, G and L and anti-kangaroo antibody.

    PubMed

    Vaz, Paola K; Hartley, Carol A; Browning, Glenn F; Devlin, Joanne M

    2015-12-01

    Serological studies are often conducted to examine exposure to infectious agents in wildlife populations. However, specific immunological reagents for wildlife species are seldom available and can limit the study of infectious diseases in these animals. This study examined the ability of four commercially available immunoglobulin-binding reagents to bind serum immunoglobulins from 17 species within the Marsupialia and Monotremata. Serum samples were assessed for binding, using immunoblots and ELISAs (Enzyme-linked immunosorbent assays), to three microbially-derived proteins - staphylococcal protein A, streptococcal protein G and peptostreptococcal protein L. Additionally, an anti-kangaroo antibody was included for comparison. The inter- and intra-familial binding patterns of the reagents to serum immunoglobulins varied and evolutionary distance between animal species was not an accurate predictor of the ability of reagents to bind immunoglobulins. Results from this study can be used to inform the selection of appropriate immunological reagents in future serological studies in these clades.

  4. Marsupial and monotreme serum immunoglobulin binding by proteins A, G and L and anti-kangaroo antibody.

    PubMed

    Vaz, Paola K; Hartley, Carol A; Browning, Glenn F; Devlin, Joanne M

    2015-12-01

    Serological studies are often conducted to examine exposure to infectious agents in wildlife populations. However, specific immunological reagents for wildlife species are seldom available and can limit the study of infectious diseases in these animals. This study examined the ability of four commercially available immunoglobulin-binding reagents to bind serum immunoglobulins from 17 species within the Marsupialia and Monotremata. Serum samples were assessed for binding, using immunoblots and ELISAs (Enzyme-linked immunosorbent assays), to three microbially-derived proteins - staphylococcal protein A, streptococcal protein G and peptostreptococcal protein L. Additionally, an anti-kangaroo antibody was included for comparison. The inter- and intra-familial binding patterns of the reagents to serum immunoglobulins varied and evolutionary distance between animal species was not an accurate predictor of the ability of reagents to bind immunoglobulins. Results from this study can be used to inform the selection of appropriate immunological reagents in future serological studies in these clades. PMID:26523413

  5. Studies on immunoglobulin gene rearrangement in formalin-fixed, paraffin-embedded pathology specimens.

    PubMed

    Dubeau, L; Weinberg, K; Jones, P A; Nichols, P W

    1988-03-01

    Studies on immunoglobulin gene rearrangement in lymphoid lesions are an increasingly important application of molecular biology in diagnostic medicine. The authors have therefore examined the possibility of detecting such rearrangements in formalin-fixed, paraffin-embedded pathology specimens. Southern blots of DNA obtained from optimally fixed tissues were very similar to blots of unfixed material, except that the electrophoretic mobility of the fixed DNA fragments was sometimes slightly reduced. High-molecular-weight DNA was not recovered from suboptimally fixed partially autolysed samples. Increasing the time of exposure to formalin resulted in loss of hybridizable DNA. Monoclonal rearrangements of heavy and light chain immunoglobulin genes could be detected in formalin-fixed specimens provided that these fixation artifacts were taken into consideration. This technique expands the pool of material available for studies on gene rearrangement and should facilitate the use of such studies in clinical medicine.

  6. High-Dose Subcutaneous Immunoglobulins for the Treatment of Severe Treatment-Resistant Polymyositis

    PubMed Central

    Patrick, Cherin; Jean-Christophe, Delain; Jean-Charles, Crave; Odile, Cartry

    2014-01-01

    Polymyositis is a rare debilitating condition characterized by chronic inflammation and muscle weakness. Standard treatments include corticosteroids and immunosuppressants; however, resistance to these regimens may develop. Intravenous immunoglobulins (IVIg) are thus recommended for patients with drug-resistant polymyositis. The patient presented a resistant polymyositis with severe muscle weakness, increasing dysphagia, and significant loss in weight. Subcutaneous immunoglobulins (SCIg) were initiated after failure of steroids and immunosuppressive drugs. SCIg was given twice per week (2 then 1.3 g/kg/month). Clinical recovery was observed within 2 months after the SCIg initiation. After several injections, the patient showed a progressive improvement in muscle strength. Serum creatine kinase activity decreased to normal levels, and dysphagia was resolved. The SC injections were generally well tolerated and good patient satisfaction was reported. This promising observation suggests that SCIg may be useful in active and refractory polymyositis. PMID:25140268

  7. Induction of Regulatory T Cells by Intravenous Immunoglobulin: A Bridge between Adaptive and Innate Immunity

    PubMed Central

    Kaufman, Gabriel N.; Massoud, Amir H.; Dembele, Marieme; Yona, Madelaine; Piccirillo, Ciriaco A.; Mazer, Bruce D.

    2015-01-01

    Intravenous immunoglobulin (IVIg) is a polyclonal immunoglobulin G preparation with potent immunomodulatory properties. The mode of action of IVIg has been investigated in multiple disease states, with various mechanisms described to account for its benefits. Recent data indicate that IVIg increases both the number and the suppressive capacity of regulatory T cells, a subpopulation of T cells that are essential for immune homeostasis. IVIg alters dendritic cell function, cytokine and chemokine networks, and T lymphocytes, leading to development of regulatory T cells. The ability of IVIg to influence Treg induction has been shown both in animal models and in human diseases. In this review, we discuss data on the potential mechanisms contributing to the interaction between IVIg and the regulatory T-cell compartment. PMID:26441974

  8. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    PubMed Central

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark

    2016-01-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  9. Serum immunoglobulins G, A and M in White and Black adults on the Witwatersrand.

    PubMed

    Shulman, G; Gilich, G C; Andrew, M J

    1975-07-12

    Blood donors and hospital inpatients of the same sex and race group showed similar concentrations of serum immunoglobulins G and M. Serum IgA levels were significantly higher in three of four hospital patient groups as compared with blood donor groups matched for sex and race. Age was shown to be responsible for this difference, since on average the blood donors were younger and analysis of all subjects in age groups showed a progressive rise in IgA with increasing age. Lower IgA levels occurred in women than in men of comparable age and race group. A sex difference with higher IgM levels in women was confirmed. All values in Black adults were much higher than in Whites. It is therefore of importance to consider the ranges of values for any individual's age, sex and race when interpreting results of serum immunoglobulin assay.

  10. Primary immunoglobulin response of herons to infection with Venezuelan encephalitis virus.

    PubMed

    Powers, C D; Dickerman, R W

    1975-02-01

    Seven to nine days after inoculation with a replicating antigen, Venezuelan encephalitis virus, hemagglutination-inhibiting antibodies were present in plasma of 18 to 20 black-crowned night herons (BCNH), 14 of 15 great egrets (ge) , and 7 of 7 snowy egrets (SE). 19S (immunoglobulin M) precedes 7S (immunoglobulin G) antibodies in all but one bird of six GE, six SE, and six BCNH. 19S antibodies were detected for only 2 to 4 weeks post-inoculation. The induction period for both types of antibody was prolonged by 2 to 6 days as compared with earlier studies in gallinaceous birds using nonreplicating antigens. A marked delay in reaching peak titer of 7S antibodies was also observed. Hemagglutination inhibition tests were nearly as sensitive as neutralization tests for detecting 19S and early 7S antibodies. Size of virus inoculum did not measurably affect time of induction or titer of antibodies.

  11. Immunoglobulin transfer and weight gains in suckled beef calves force-fed stored colostrum.

    PubMed

    Bradley, J A; Niilo, L

    1985-04-01

    Concentrations of immunoglobulins and total proteins in second-day post-partum serum samples of 62 beef calves from multiparous dams were measured by zinc sulphate turbidity, electrophoresis, radial immunodiffusion and refractometry. These results, together with health records and weight gains, were used to evaluate the practice of routinely force-feeding 1 L of stored colostrum to suckled beef calves immediately after birth. There was no apparent benefit from such force-feeding. It did not result in greater 48-hour serum immunoglobulin levels, nor did it improve weight gains at 42 days. None of the calves required treatment for neonatal disease, but one force-fed calf died from inhalation of regurgitated colostrum.

  12. Immunoglobulin and complement in tissues of mice infected with Nocardia brasiliensis.

    PubMed Central

    Conde, C; Mancilla, R; Fresan, M; Ortiz-Ortiz, L

    1983-01-01

    Two weeks after mice had been infected in the footpad with cells of Nocardia brasiliensis, immunoglobulin and C3 deposits were observed in tissue from the inoculation site. Both immunoglobulin and C3 were found in the actinomycotic granules that characterize the mycetoma and in the surrounding inflammatory zones, in which plasma cells were also present. Although anti-N. brasiliensis specificity was evidenced at 14 days postinfection in an eluate of infected tissue by an immunoenzymatic assay, no such antibody was found in the serum until 45 days postinfection. Immune complexes in the lesions, as indicated by the presence of C3, may also contribute to the pathology of the disease. Images PMID:6852920

  13. Single-mode tapered optical fiber loop immunosensor II: assay of anti-cholera toxin immunoglobulins

    NASA Astrophysics Data System (ADS)

    Marks, Robert S.; Hale, Zoe M.; Levine, Myron M.; Lowe, C. R.; Payne, Frank P.

    1994-07-01

    An evanescent wave immunoassay for cholera antitoxin immunoglobulins was performed using a single mode tapered optical fiber loop sensor. The transducer was silanized with 3- glycidoxypropyltrimethoxysilane and chemically modified to link covalently either cholera toxin B subunit or a synthetic peptide derived from it, CTP3. The sensor was exposed to seral fluids, obtained from human volunteers having been exposed to live virulent Vibrio cholerae 01 and shown to produce rice-water stools. Other toxins of interest, such as Clostridium botulinum toxin A, have been tested on similar systems. The bound unlabelled immunoglobulins were then exposed to a mixture of FITC-anti-IgG and TRITC-anti-IgA, without requirement for a separation step. The emanating fluorescent emissions of fluorescein and rhodamine, excited by the input laser light, were coupled back into the guided mode of the tapered fiber, and used to determine the concentrations of the complementary antigens.

  14. Immunoglobulin heavy chain/light chain pairs (HLC, Hevylite™) assays for diagnosing and monitoring monoclonal gammopathies.

    PubMed

    Kraj, Maria

    2014-01-01

    Immunofixation (IFE) is a standard method for detecting monoclonal immunoglobulins and characterizing its isotype. Recently clonality can also be determined by using immunoglobulin (Ig) heavy chain/light chain immunoassays - HLC, HevyliteTM. HLC separately measures in pairs light chain types of each intact Ig class generating ratios of monoclonal Ig/uninvolved polyclonal Ig concentrations. Studies have shown that HLC and IFE are complementary methods. HLC assays quantify monoclonal proteins and identify monoclonality. It is possible to predict prognosis in multiple myeloma and to monitor response to treatment using HLC ratio. HLC ratio may serve as a parameter for myeloma induced immunoparesis and serve as a new marker for validating remission depth and relapse probabilities.

  15. Construction of recombinant plasmids containing Xenopus immunoglobulin heavy chain DNA sequences.

    PubMed Central

    Brown, R D; Armentrout, R W; Cochran, M D; Cappello, J; Langemeier, S O

    1981-01-01

    A recombinant cDNA plasmid containing Xenopus immunoglobulin heavy chain sequence has been constructed from Xenopus spleen poly(A)-containing RNA. The plasmid was identified by colony hybridization and a hybridization-translation assay and its identity was confirmed by DNA sequence analysis. The portion of the heavy chain sequence contained in the plasmid is 35% homologous to mammalian mu and gamma sequences. The mRNA corresponding to this plasmid is 2.5 kilobases, in close agreement with the size of mouse mu mRNA. RNA sequences complementary to the cloned sequence appear in embryos about 24 hr after fertilization, which corresponds to 24 hr before the first detectable immunoglobulin. Images PMID:6112748

  16. Identification of a DNA binding protein that recognizes the nonamer recombinational signal sequence of immunoglobulin genes.

    PubMed

    Halligan, B D; Desiderio, S V

    1987-10-01

    Extracts of nuclei from B- and T-lymphoid cells contain a protein that binds specifically to the conserved nonamer DNA sequence within the recombinational signals of immunoglobulin genes. Complexes with DNA fragments from four kappa light-chain joining (J) segments have the same electrophoretic mobility. Nonamer-containing DNA fragments from heavy-chain and light-chain genes compete for binding. Within the 5'-flanking DNA of the J kappa 4 gene segment, the binding site has been localized to a 27-base-pair interval spanning the nonamer region. The binding activity is recovered as a single peak after ion-exchange chromatography. The site of binding of the protein and its presence in nuclei of lymphoid cells suggest that it may function in the assembly of immunoglobulin genes.

  17. When conventional treatment fails: the role of intravenous immunoglobulin in recurrent pregnancy loss secondary to antiphospholipid syndrome

    PubMed Central

    Chay, Jacklyn; Lust, Karin; Kubler, Paul; Callaway, Leonie

    2013-01-01

    Recurrent pregnancy loss (RPL) is a well-recognized complication of antiphospholipid syndrome (APS). First line therapy consists of low dose aspirin and heparin. Despite conventional therapy some women fail to achieve a successful pregnancy outcome. We describe the case of a patient who had two live births following intravenous immunoglobulin therapy despite previous failure with conventional therapy for RPL in the setting of APS. We will summarize the available literature on intravenous immunoglobulin for this indication.

  18. Protection of monkeys against Machupo virus by the passive administration of Bolivian haemorrhagic fever immunoglobulin (human origin).

    PubMed

    Eddy, G A; Wagner, F S; Scott, S K; Mahlandt, B J

    1975-01-01

    Bolivian haemorrhagic fever immunoglobulin of human origin, given either prior to or shortly after experimental infection with Machupo virus, protected rhesus and cynomolgus monkeys against initial clinical illness. Some survivors developed severe neurological signs 30-47 days after virus inoculation and died 4-6 days later. Results from one of the experiments suggested that the development of neurological signs was associated more frequently with high doses of immunoglobulin than with intermediate or low doses.

  19. Quantitative assessment of hemadsorption by myxoviruses: anti-immunoglobulin G hemadsorption-inhibition test.

    PubMed

    Hahon, N; Stewart, J D; Eckert, H L

    1973-04-01

    A quantitative hemadsorption-inhibition test was developed to estimate myxovirus serum antibodies within 24 h by determining the serum dilution inhibiting hemadsorption in 50% of the infected cells. The test depends on the interactions of virus-infected cell monolayers with antiviral serum and of the resultant complexes with antiimmunoglobulin G serum. The incorporation of species-specific anti-immunoglobulin G serum into the test significantly increased sensitivity. PMID:4349249

  20. Onset of immune senescence defined by unbiased pyrosequencing of human immunoglobulin mRNA repertoires.

    PubMed

    Rubelt, Florian; Sievert, Volker; Knaust, Florian; Diener, Christian; Lim, Theam Soon; Skriner, Karl; Klipp, Edda; Reinhardt, Richard; Lehrach, Hans; Konthur, Zoltán

    2012-01-01

    The immune system protects us from foreign substances or pathogens by generating specific antibodies. The variety of immunoglobulin (Ig) paratopes for antigen recognition is a result of the V(D)J rearrangement mechanism, while a fast and efficient immune response is mediated by specific immunoglobulin isotypes obtained through class switch recombination (CSR). To get a better understanding on how antibody-based immune protection works and how it changes with age, the interdependency between these two parameters need to be addressed. Here, we have performed an in depth analysis of antibody repertoires of 14 healthy donors representing different gender and age groups. For this task, we developed a unique pyrosequencing approach, which is able to monitor the expression levels of all immunoglobulin V(D)J recombinations of all isotypes including subtypes in an unbiased and quantitative manner. Our results show that donors have individual immunoglobulin repertoires and cannot be clustered according to V(D)J recombination patterns, neither by age nor gender. However, after incorporating isotype-specific analysis and considering CSR information into hierarchical clustering the situation changes. For the first time the donors cluster according to age and separate into young adults and elderly donors (>50). As a direct consequence, this clustering defines the onset of immune senescence at the age of fifty and beyond. The observed age-dependent reduction of CSR ability proposes a feasible explanation why reduced efficacy of vaccination is seen in the elderly and implies that novel vaccine strategies for the elderly should include the "Golden Agers". PMID:23226220

  1. Immunoglobulin fragments, F(ab')2, that are cytotoxic to enzyme-treated cells.

    PubMed

    Holtgrewe, E M; Killion, J J

    1984-07-01

    Bivalent immunoglobulin fragments of IgG, F(ab')2, prepared from normal murine sera were found to be cytotoxic to neuraminidase-treated cells. The fragments were cytotoxic to both allogenic and syngeneic targets (with respect to the source of the sera), suggesting that the antigen bound by the F(ab')2 is not related to the major histocompatibility locus of mice (H-2).

  2. Mannosylerythritol lipid, a yeast extracellular glycolipid, shows high binding affinity towards human immunoglobulin G

    PubMed Central

    Im, Jae Hong; Nakane, Takashi; Yanagishita, Hiroshi; Ikegami, Toru; Kitamoto, Dai

    2001-01-01

    Background There have been many attempts to develop new materials with stability and high affinity towards immunoglobulins. Some of glycolipids such as gangliosides exhibit a high affinity toward immunoglobulins. However, it is considerably difficult to develop these glycolipids into the practical separation ligand due to their limited amounts. We thus focused our attention on the feasible use of "mannosylerythritol lipid A", a yeast glycolipid biosurfactant, as an alternative ligand for immunoglobulins, and undertook the investigation on the binding between mannosylerythritol lipid A (MEL-A) and human immunoglobulin G (HIgG). Results In ELISA assay, MEL-A showed nearly the same binding affinity towards HIgG as that of bovine ganglioside GM1. Fab of human IgG was considered to play a more important role than Fc in the binding of HIgG by MEL-A. The bound amount of HIgG increased depending on the attached amount of MEL-A onto poly (2-hydroxyethyl methacrylate) (polyHEMA) beads, whereas the amount of human serum albumin slightly decreased. Binding-amount and -selectivity of HIgG towards MEL-A were influenced by salt species, salt concentration and pH in the buffer solution. The composite of MEL-A and polyHEMA, exhibited a significant binding constant of 1.43 × 106 (M-1) for HIgG, which is approximately 4-fold greater than that of protein A reported. Conclusions MEL-A shows high binding-affinity towards HIgG, and this is considered to be due to "multivalent effect" based on the binding molar ratio. This is the first report on the binding of a natural human antibody towards a yeast glycolipid. PMID:11604104

  3. Increased immunoglobulin G production by short term cultured duodenal biopsy samples from HIV infected patients

    PubMed Central

    Schneider, T; Zippel, T; Schmidt, W; Pauli, G; Wahnschaffe, U; Chakravarti, S; Heise, W; Riecken, E; Zeitz, M; Ullrich, R

    1998-01-01

    Background—Secretory immunity is a major defence mechanism against infections at mucosal surfaces which are common in HIV infected patients. 
Aims—To analyse intestinal immunoglobulin production in HIV infection in comparison with that in saliva and serum. 
Patients and methods—Immunoglobulin G (IgG), A (IgA), and M (IgM) concentrations were determined in supernatants of short term cultured duodenal biopsy samples, serum, and saliva from HIV infected patients (n = 28) and controls (n = 14) by radial immunodiffusion. 
Results—IgG was increased in the supernatants of short term cultured biopsy samples and saliva from HIV infected patients compared with controls (p<0.01), but IgA and IgM levels were normal. In contrast, both IgG and IgA concentrations in serum were higher in HIV infected patients than in controls (p<0.002). No correlation was found between IgA produced by duodenal biopsy specimens and serum IgA. 
Conclusion—Abnormalities in mucosal immunoglobulin production in HIV infection were suprisingly small, indicating that specific secretory immunity rather than quantitative immunoglobulin production may be impaired. However, increased production of IgG could contribute to mucosal inflammation by complement activation. Our findings of normal mucosal IgA production and the lack of correlation between serum and mucosal IgA argues against an intestinal origin for the increased serum IgA levels in HIV infected patients. 

 Keywords: mucosal immunity; HIV infection; intestinal antibodies PMID:9577341

  4. Examination of Glycan Profiles from IgG-Depleted Human Immunoglobulins Facilitated by Microscale Affinity Chromatography

    PubMed Central

    Svoboda, Martin; Mann, Benjamin F.; Goetz, John A.; Novotny, Milos V.

    2012-01-01

    Among the most important proteins involved in the disease and healing processes are the immunoglobulins (Igs). Although many of the Igs have been studied through proteomics, aside from IgG, immunoglobulin carbohydrates have not been extensively characterized in different states of health. It seems valuable to develop techniques that permit us to understand changes in the structures and abundances of Ig glycans in the context of disease onset and progression. We have devised a strategy for characterization of the glycans for the Ig classes other than IgG (i.e. A, D, E, and M) that contain kappa light chains, while using only a few microliters of biological material. First, we designed a microcolumn containing the recombinant Protein L that was immobilized on macroporous silica particles. A similarly designed Protein G microcolumn was utilized to first perform an on-line depletion of the IgG from the sample, human blood serum, and thereby facilitate enrichment of the other Igs. While only 3 μL of serum were used in these analyses, we were able to recover a significantly-enriched fraction of non-IgG immunoglobulins. The enrichment properties of the Protein L column were characterized using a highly sensitive label-free quantitative proteomics LC-MS/MS approach, and the glycomic profiles of enriched immunoglobulins were measured by MALDI-TOF-MS. As a proof-of-principle, a comparative study was conducted using blood serum from a small group of lung cancer patients and a group of age-matched cancer-free individuals to demonstrate that the method is suitable for investigation of glycosylation changes in disease. The results were in agreement with a glycomic investigation of whole blood serum from a much larger lung cancer cohort. PMID:22360417

  5. Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice

    NASA Astrophysics Data System (ADS)

    Brinster, Ralph L.; Ritchie, Kindred A.; Hammer, Robert E.; O'Brien, Rebecca L.; Arp, Benjamin; Storb, Ursula

    1983-11-01

    Transgenic mice were produced by microinjection of a rearranged, functional immunoglobulin κ gene into fertilized mouse eggs and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were mated and the DNA, RNA and serum κ chains of their offspring were analysed. The data from offspring of three different transgenic mice indicate that the microinjected gene is expressed in the spleen, but not the liver of mice which inherited the injected gene.

  6. Humoral immunoglobulins of the white sturgeon, Acipenser transmontanus: partial characterization of and recognition with monoclonal antibodies.

    PubMed

    Adkison, M A; Basurco, B; Hedrick, R P

    1996-01-01

    White sturgeon (Acipenser transmontanus) immunoglobulin (Ig) was purified from serum by two methods, ion-exchange chromatography and gel filtration and precipitation of the euglobulin fraction. The purity of these immunoglobulin preparations was confirmed by gel electrophoresis. Sequence analysis of the N-terminal amino acids confirmed that the purified protein was immunoglobulin. The major portion of the immunoglobulin preparation consisted of two proteins with estimated molecular weights (m.w.) of 870 and 170 kDa. The m.w. of the H- and L-chains of the purified Ig were 73 and 27-30 kDa, respectively, as determined by SDS-PAGE. Ion-exchange purified Ig was used to immunize mice for the production of monoclonal antibodies. This resulted in the production of six stable hybrids that recognized sturgeon Ig, two specific for heavy chain and four specific for light chain. The two anti-H-chain mabs were highly specific for white sturgeon Ig while all four anti-L-chain mabs cross reacted with Ig from green sturgeon (A. medirostris), Atlantic sturgeon (A. oxyrhynchus oxyrhynchus), shovelnose sturgeon (Scaphirhynchus platorynchus), and paddlefish (Polyodon spathula), (all Chondrosteans), but not with channel catfish (Ictalurus punctatus), rainbow trout (Oncorhynchus mykiss) or striped bass (Morone saxatilis). The mabs were used to enumerate the percentage of sIg+ lymphocytes in the peripheral blood of white sturgeon by flow cytometry. The percentage of cells positively stained with the mabs ranged from 12 to 28%. In a comparison of mabs with polyclonal rabbit anti-sturgeon Ig serum by ELISA the mabs produced a larger signal and less background than the polyclonal serum.

  7. Sequence of the dog immunoglobulin alpha and epsilon constant region genes

    SciTech Connect

    Patel, M.; Selinger, D.; Mark, G.E.; Hollis, G.F.; Hickey, G.J.

    1995-03-01

    The immunoglobulin alpha (IGHAC) and epsilon (IGHEC) germline constant region genes were isolated from a dog liver genomic DNA library. Sequence analysis indicates that the dog IGHEC gene is encoded by four exons spread out over 1.7 kilobases (kb). The IGHAC sequence encompasses 1.5 kb and includes all three constant region coding exons. The complete exon/intron sequence of these genes is described. 28 refs., 2 figs., 2 tabs.

  8. Generation and characterization of polyclonal antibody against part of immunoglobulin constant heavy υ chain of goose.

    PubMed

    Zhao, Panpan; Guo, Yongli; Ma, Bo; Xing, Mingwei; Wang, Junwei

    2014-08-01

    Immunoglobulin Y (abbreviated as IgY) is a type of immunoglobulin that is the major antibody in bird, reptile, and lungfish blood. IgY consists of two light (λ) and two heavy (υ) chains. In the present study, polyclonal antibody against IgYFc was generated and evaluated. rIgYCυ3/Cυ4 was expressed in Escherichia coli, purified and utilized to raise polyclonal antibody in rabbit. High affinity antisera were obtained, which successfully detected the antigen at a dilution of 1:204,800 for ELISA assay. The antibody can specifically recognize both rIgYCυ3/Cυ4 and native IgY by Western bolt analysis. Furthermore, the serum of Grus japonensis or immunoglobulin of chicken, duck, turkey, and silkie samples and dynamic changes of serum GoIgY after immunogenicity with GPV-VP3-virus-like particles (GPV-VP3-VLPs) can be detected with the anti-GoIgYFc polyclonal antibody. These results suggested that the antibody is valuable for the investigation of biochemical properties and biological functions of GoIgY.

  9. Production of immunoglobulins in gingival tissue explant cultures from juvenile periodontitis patients

    SciTech Connect

    Hall, E.R.; Falkler, W.A. Jr.; Suzuki, J.B. )

    1990-10-01

    B lymphocytes and plasma cells are histologically observed in granulomatous periodontal tissues of juvenile periodontitis (JP) patients. Local immune processes may participate in protective or immunopathologic roles in the pathogenesis of this disease. An in vitro explant culture system was utilized to demonstrate the production of immunoglobulins by diseased JP tissues. Immunodiffusion studies using goat anti-human gamma, alpha, or mu chain serum revealed IgG to be the major immunoglobulin present in 92% of the day 1 supernatant fluids (SF) of the 47 JP gingival tissue explant cultures. IgA was present in 15% of the SF; however, no IgM was detected. Staph Protein A isolated 14C-labeled IgG from the SF, when allowed to react with goat anti-human gamma chain serum, formed lines of precipitation. Positive autoradiographs confirmed the biosynthesis of IgG by the explant cultures. The in vitro gingival tissue explant culture system described provides a useful model for the study of localized immunoglobulins produced by diseased tissues of JP patients.

  10. Immunoglobulin Transporting Receptors Are Potential Targets for the Immunity Enhancement and Generation of Mammary Gland Bioreactor

    PubMed Central

    Jiang, Xuemei; Hu, Jianjun; Thirumalai, Diraviyam; Zhang, Xiaoying

    2016-01-01

    The functions of immunoglobulin transporting receptors (Ig transporting receptors) in immune system encompass from passive immunity to adaptive immunity by transporting immunoglobulins (Igs) and prolonging their half-life as well as enhancing immunosurveillance. Prior to the weaning, Ig transportations from mother to offspring confer the immediate passive immunity for neonates. After the weaning, FcRn and polymeric immunoglobulin receptor on infant intestinal epithelial cells retrieve Ig in intestinal lamina propria into the gut lumen for preventing pathogen invasion. This is not only improving the pathological consequences of infection but also helping the neonates for developing their own immune response; besides it would be the guidance for designing novel vaccines. Moreover, the investigations on Ig transporting receptors over-expressed transgenic animals have been carried out to improve Ig concentrations in serum and milk; thus, it would be a sustainable method to produce antibody-enriched milk-derived colostrum replacer for neonates. In order to generate mammary gland bioreactor, a series of methods have been developed for enhanced regulation of Ig transporting receptors expression and Ig transportation. PMID:27375616

  11. Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta)

    SciTech Connect

    Stone, W.H.; Hackleman, S.M.; Braun, A.M.; Pennington, P.; Saphire, D.G.; Scheffler, J.; Wigle, J.C.; Cox, A.B.

    1994-06-01

    We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure of protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age. 48 refs., 2 figs., 4 tabs.

  12. Immunoglobulin G response to subgingival gram-negative bacteria in human subjects.

    PubMed Central

    Naito, Y; Okuda, K; Takazoe, I

    1984-01-01

    Serum and gingival crevicular fluid from normal healthy adults and patients with periodontitis were screened for immunoglobulin G antibodies to antigens from Bacteroides gingivalis 381, Bacteroides intermedius 24, Bacteroides loescheii ATCC 15930, Fusobacterium nucleatum ATCC 25586, Eikenella corrodens 1073, Actinobacillus actinomycetemcomitans ATCC 29522, and Capnocytophaga sp. strain M-12. Immunoglobulin G antibody titers to the antigens were measured by an enzyme-linked immunosorbent assay. The antibody levels to B. gingivalis in serum and gingival crevicular fluid were significantly higher in the samples from patients with periodontitis than in samples from healthy individuals. Although there were individual differences within patient groups, a positive correlation (P less than 0.01) was found between the serum immunoglobulin G levels to B. gingivalis and the development of periodontitis. The antibodies to F. nucleatum (P less than 0.05), E. corrodens (P less than 0.05), and A. actinomycetemcomitans were slightly higher in patients with periodontitis than in normal subjects. There were no remarkable differences between the two groups in titers to B. intermedius, B. loescheii, and Capnocytophaga sp. PMID:6735473

  13. Phage Display Based Cloning of Proteins Interacting with the Cytoplasmic Tail of Membrane Immunoglobulins

    PubMed Central

    Geisberger, Roland; Prlic, Martin; Achatz-Straussberger, Gertrude; Oberndorfer, Iris; Luger, Elke; Lamers, Marinus; Crameri, Reto; Appenzeller, Ulrich; Wienands, Jürgen; Breitenbach, Michael; Ferreira, Fatima; Achatz, Gernot

    2002-01-01

    The reduced quantity and quality of serum immunoglobulins (sIgs) in mutant mice expressing truncated cytoplasmic tails of IgE and IgG1 indicate an active role for the cytoplasmic domains of mIgG1 and mIgE. We used phage display technology to identify candidate proteins able to interact with the cytoplasmic tail of mIgE. Using a murine cDNA B cell library displayed on the surface of phage as prey and the 28 amino acid long cytoplasmic tail of IgE as bait, we isolated phage encoding the murine hematopoietic progenitor kinase 1 (HPK1). Surface plasmon resonance analysis measurements confirmed affinity of HPK1 to the mIgE cytoplasmic tail and revealed association to other immunoglobulin isotypes as well. Immunoprecipitation experiments, using lysates from two B cell lines expressing nitrophenyl (NP) specific mIgE molecules showed co-precipitation of IgE and HPK1. The interaction of HPK1 with the cytoplasmic domains of membrane immunoglobulins indicate an active role of the tails as part of an isotype specific signal transduction, independent from the Igα/Igβ heterodimers, and may represent a missing link to upstream regulatory elements of HPK1 activation. PMID:12885153

  14. Limited number of immunoglobulin VH regions expressed in the mutant rabbit "Alicia".

    PubMed

    DiPietro, L A; Short, J A; Zhai, S K; Kelus, A S; Meier, D; Knight, K L

    1990-06-01

    A unique feature of rabbit Ig is the presence of VH region allotypic specificities. In normal rabbits, more than 80% of circulating immunoglobulin molecules bear the VHa allotypic specificities, al, a2 or a3; the remaining 10% to 20% of immunoglobulin molecules lack VHa allotypic specificities and are designated VHa-. A mutant rabbit designated Alicia, in contrast, has predominantly serum immunoglobulin molecules that lack the VHa allotypic specificities (Kelus and Weiss, Proc. Natl. Acad. Sci. USA 1986. 83: 4883). To study the nature and molecular complexity of VHa- molecules, we cloned and determined the nucleotide sequence of seven cDNA prepared from splenic RNA of an Alicia rabbit. Six of the clones appeared to encode VHa- molecules; the framework regions encoded by these clones were remarkably similar to each other, each having an unusual insertion of four amino acids at position 10. This insertion of four amino acids has been seen in only 2 of 54 sequenced rabbit VH genes. The similarity of the sequences of the six VHa- clones to each other and their dissimilarity to most other VH genes leads us to suggest that the VHa- molecules in Alicia rabbits are derived predominantly from one or a small number of very similar VH genes. Such preferential utilization of a small number of VH genes may explain the allelic inheritance of VH allotypes.

  15. Immunoglobulin Transporting Receptors Are Potential Targets for the Immunity Enhancement and Generation of Mammary Gland Bioreactor.

    PubMed

    Jiang, Xuemei; Hu, Jianjun; Thirumalai, Diraviyam; Zhang, Xiaoying

    2016-01-01

    The functions of immunoglobulin transporting receptors (Ig transporting receptors) in immune system encompass from passive immunity to adaptive immunity by transporting immunoglobulins (Igs) and prolonging their half-life as well as enhancing immunosurveillance. Prior to the weaning, Ig transportations from mother to offspring confer the immediate passive immunity for neonates. After the weaning, FcRn and polymeric immunoglobulin receptor on infant intestinal epithelial cells retrieve Ig in intestinal lamina propria into the gut lumen for preventing pathogen invasion. This is not only improving the pathological consequences of infection but also helping the neonates for developing their own immune response; besides it would be the guidance for designing novel vaccines. Moreover, the investigations on Ig transporting receptors over-expressed transgenic animals have been carried out to improve Ig concentrations in serum and milk; thus, it would be a sustainable method to produce antibody-enriched milk-derived colostrum replacer for neonates. In order to generate mammary gland bioreactor, a series of methods have been developed for enhanced regulation of Ig transporting receptors expression and Ig transportation. PMID:27375616

  16. A human follicular lymphoma B cell line hypermutates its functional immunoglobulin genes in vitro.

    PubMed

    Wu, H; Pelkonen, E; Knuutila, S; Kaartinen, M

    1995-12-01

    The functional immunoglobulin (Ig) genes of B lymphocytes undergo somatic mutations during immune responses. These mutations modify the antigen binding site of the immunoglobulins, thereby enhancing the average affinity of the antibodies produced. The molecular mechanism underlying these B cell hypermutations remains unresolved, partly because it is difficult to grow normal B cells in long-term cell cultures and because there is no suitable transformed or malignant B cell line which generates mutations in its immunoglobulin genes in vitro. Here, we show that the recently established follicular lymphoma line HF-1.3.4 generates somatic hypermutations in vitro at a high frequency of 0.7 x 10(-6) mutations per base pair per generation in standard cell cultures (RPMI 1640 + 5% fetal calf serum). This shows for the first time that B cell hypermutation can occur without T cells or T cell factors. The mutation frequency increased approximately tenfold to 1 x 10(-5) mutations/base pair/generation with B cell-specific growth factors (interleukins-2 and -4 and three antibodies stimulatory to HF-1.3.4 cells). This HF-1.3.4 lymphoma line may help to elucidate the molecular mechanism of Ig gene hypermutation.

  17. Importance of killer immunoglobulin-like receptors in allogeneic hematopoietic stem cell transplantation

    PubMed Central

    Franceschi, Danilo Santana Alessio; de Souza, Cármino Antonio; Aranha, Francisco José Penteado; Cardozo, Daniela Maira; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

    2011-01-01

    Hematopoietic stem cell transplantation is the treatment of choice for many hematologic diseases, such as multiple myeloma, bone marrow aplasia and leukemia. Human leukocyte antigen (HLA) compatibility is an important tool to prevent post-transplant complications such as graft rejection and graft-versus-host disease, but the high rates of relapse limit the survival of transplant patients. Natural Killer cells, a type of lymphocyte that is a key element in the defense against tumor cells, cells infected with viruses and intracellular microbes, have different receptors on their surfaces that regulate their cytotoxicity. Killer immunoglobulin-like receptors are the most important, interacting consistently with human leukocyte antigen class I molecules present in other cells and thus controlling the activation of natural killer cells. Several studies have shown that certain combinations of killer immunoglobulin-like receptors and human leukocyte antigens (in both donors and recipients) can affect the chances of survival of transplant patients, particularly in relation to the graft-versusleukemia effect, which may be associated to decreased relapse rates in certain groups. This review aims to shed light on the mechanisms and effects of killer immunoglobulin-like receptors - human leukocyte antigen associations and their implications following hematopoietic stem cell transplantation, and to critically analyze the results obtained by the studies presented herein. PMID:23284260

  18. Uniform detection of immunoglobulin-gene rearrangement in benign lymphoepithelial lesions.

    PubMed

    Fishleder, A; Tubbs, R; Hesse, B; Levine, H

    1987-04-30

    The term "benign lymphoepithelial lesion" is used to describe the salivary-gland lymphocytic infiltration and epithelial changes typically found in association with Sjögren's syndrome. We used Southern blot hybridization techniques to examine the immunoglobulin genes in salivary-gland tissue derived from eight patients with benign lymphoepithelial lesions. Three of these patients had intrasalivary non-Hodgkin's lymphoma complicating the lesions, whereas the lesions in the remaining five were all histologically benign. Ten samples from the eight patients all revealed rearrangement of both the heavy-chain and light-chain immunoglobulin genes. In one of the patients in whom non-Hodgkin's lymphoma involved both the salivary-gland lesion and an ipsilateral lymph node, the rearrangements of the heavy-chain and light-chain immunoglobulin genes detected at the two sites were identical. One other patient had two distinct benign lymphoepithelial lesions removed two years apart. The rearrangements of the heavy-chain as well as the kappa light-chain genes detected in these two lesions were entirely different. These data suggest that B-cell clonal expansion has an integral role in the pathophysiology of the benign lymphoepithelial lesion and may explain the increased incidence of lymphoma noted in association with this disorder.

  19. Uptake and localization of /sup 131/I-labeled anti-calcitonin immunoglobulins in rat medullary thyroid carcinoma tissue

    SciTech Connect

    Gautvik, K.M.; Svindahl, K.; Skretting, A.; Stenberg, B.; Myhre, L.; Ekeland, A.; Johannesen, J.V.

    1982-09-15

    A medullary carcinoma of the thyroid gland (MCT) which has been transplanted repeatedly under the kidney capsule of Wag/Rij rats secretes calcitonin (CT) spontaneously. From 10--20 weeks after transplantation, immunoreactive serum calcitonin (iCT) is abnormally elevated and continues to rise parallel to tumor growth. The immunoglobulin fraction of the rabbit anti-CT antiserum raised against intact synthetic hormone, was purified and iodinated electrolytically. Specific activities of /sup 131/I-labeled immunoglobulin of 0.008--0.014 mCi/microgram protein were obtained with 80% preservation of CT binding activity. Wag/Rig rats with MCT tumor and increased serum iCT concentrations received intravenous injections of /sup 131/I-labeled immunoglobulins (0.054--0.811 mCi). The distribution of radioactivity in the rats was followed for 14 days using external scintigraphy in combination with radioactivity measurements of blood and different organs at the end of the observation period. The distribution of /sup 113/mIn was used as a marker for blood distribution. When the radioactivity ratios (/sup 131/I//sup 113/mIn) in tumor and different organs were related to that of blood which was set equal to unity, tumor tissue contained 3--6 times higher activity. Nonhyperimmune rabbit immunoglobulins or rabbit antirat prolactin immunoglobulins were not concentrated in MCT tissue, nor did anti-CT immunoglobulins localize in rat prolactin adenomas.

  20. Identification of secreted and membrane-bound bat immunoglobulin using a Microchiropteran-specific mouse monoclonal antibody.

    PubMed

    Lee, William T; Jones, Derek D; Yates, Jennifer L; Winslow, Gary M; Davis, April D; Rudd, Robert J; Barron, Christopher T; Cowan, Cailyn

    2016-12-01

    Bat immunity has received increasing attention because some bat species are being decimated by the fungal disease, White Nose Syndrome, while other species are potential reservoirs of zoonotic viruses. Identifying specific immune processes requires new specific tools and reagents. In this study, we describe a new mouse monoclonal antibody (mAb) reactive with Eptesicus fuscus immunoglobulins. The epitope recognized by mAb BT1-4F10 was localized to immunoglobulin light (lambda) chains; hence, the mAb recognized serum immunoglobulins and B lymphocytes. The BT1-4F10 epitope appeared to be restricted to Microchiropteran immunoglobulins and absent from Megachiropteran immunoglobulins. Analyses of sera and other E. fuscus fluids showed that most, if not all, secreted immunoglobulins utilized lambda light chains. Finally, mAb BT1-4F10 permitted the identification of B cell follicles in splenic white pulp. This Microchiropteran-specific mAb has potential utility in seroassays; hence, this reagent may have both basic and practical applications for studying immune process. PMID:27377583