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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.

  2. Genomic variation in the porcine immunoglobulin lambda variable region.

    PubMed

    Guo, Xi; Schwartz, John C; Murtaugh, Michael P

    2016-04-01

    Production of a vast antibody repertoire is essential for the protection against pathogens. Variable region germline complexity contributes to repertoire diversity and is a standard feature of mammalian immunoglobulin loci, but functional V region genes are limited in swine. For example, the porcine lambda light chain locus is composed of 23 variable (V) genes and 4 joining (J) genes, but only 10 or 11 V and 2 J genes are functional. Allelic variation in V and J may increase overall diversity within a population, yet lead to repertoire holes in individuals lacking key alleles. Previous studies focused on heavy chain genetic variation, thus light chain allelic diversity is not known. We characterized allelic variation of the porcine immunoglobulin lambda variable (IGLV) region genes. All intact IGLV genes in 81 pigs were amplified, sequenced, and analyzed to determine their allelic variation and functionality. We observed mutational variation across the entire length of the IGLV genes, in both framework and complementarity determining regions (CDRs). Three recombination hotspot motifs were also identified suggesting that non-allelic homologous recombination is an evolutionarily alternative mechanism for generating germline antibody diversity. Functional alleles were greatest in the most highly expressed families, IGLV3 and IGLV8. At the population level, allelic variation appears to help maintain the potential for broad antibody repertoire diversity in spite of reduced gene segment choices and limited germline sequence modification. The trade-off may be a reduction in repertoire diversity within individuals that could result in an increased variation in immunity to infectious disease and response to vaccination.

  3. Genomic variation in the porcine immunoglobulin lambda variable region

    PubMed Central

    Guo, Xi; Schwartz, John C.; Murtaugh, Michael P.

    2016-01-01

    Production of a vast antibody repertoire is essential for protection against pathogens. Variable region germline complexity contributes to repertoire diversity and is a standard feature of mammalian immunoglobulin loci, but functional V region genes are limited in swine. For example, the porcine lambda light chain locus is composed of 23 variable (V) genes and 4 joining (J) genes, but only 10 or 11 V and 2 J genes are functional. Allelic variation in V and J may increase overall diversity within a population, yet lead to repertoire holes in individuals lacking key alleles. Previous studies focused on heavy chain genetic variation, thus light chain allelic diversity is not known. We characterized allelic variation of the porcine immunoglobulin lambda variable (IGLV) region genes. All intact IGLV genes in 81 pigs were amplified, sequenced, and analyzed to determine their allelic variation and functionality. We observed mutational variation across the entire length of the IGLV genes, in both framework and complementarity determining regions (CDRs). Three recombination hotspots were also identified, suggesting that non-allelic homologous recombination is an evolutionarily alternative mechanism for generating germline antibody diversity. Functional alleles were greatest in the most highly expressed families, IGLV3 and IGLV8. At the population level, allelic variation appears to help maintain the potential for broad antibody repertoire diversity in spite of reduced gene segment choices and limited germline sequence modification. The trade-off may be a reduction in repertoire diversity within individuals that could result in increased variation in immunity to infectious disease and response to vaccination. PMID:26791019

  4. Patterns of Somatic Mutations in Immunoglobulin Variable Genes

    PubMed Central

    Golding, G. Brian; Gearhart, Patricia J.; Glickman, Barry W.

    1987-01-01

    The mechanism responsible for somatic mutation in the variable genes of antibodies is unknown and may differ from previously described mechanisms that produce mutation in DNA. We have analyzed 421 somatic mutations from the rearranged immunoglobulin variable genes of mice to determine (1) if the nucleotide substitutions differ from those generated during meiosis and (2) if the presence of nearby direct and inverted repeated sequences could template mutations around the variable gene. The results reveal a difference in the pattern of substitutions obtained from somatic mutations vs. meiotic mutations. An increased frequency of T:A to C:G transitions and a decreased frequency of mutations involving a G in the somatic mutants compared to the meiotic mutants is indicated. This suggests that the mutational processes responsible for somatic mutation in antibody genes differs from that responsible for mutation during meiosis. An analysis of the local DNA sequences revealed many direct repeats and palindromic sequences that were capable of templating some of the known mutations. Although additional factors may be involved in targeting mutations to the variable gene, mistemplating by nearby repeats may provide a mechanism for the enhancement of somatic mutation. PMID:3557109

  5. Immunoglobulin variable region structure and B-cell malignancies.

    PubMed

    Kiyoi, H; Naoe, T

    2001-01-01

    The enormous diversity of immunoglobulin (Ig) variable (V) gene sequences encoding the antibody repertoire are formed by the somatic recombination of relatively few genetic elements. In B-lineage malignancies, Ig gene rearrangements have been widely used for determining clonality and cell origin. The recent development of rapid cloning and sequencing techniques has resulted in a substantial accumulation of IgV region sequences at various stages of B-cell development and has revealed stage-specific trends in the use of V, diversity, joining genes, the degree of noncoding nucleotide addition, and the rate of somatic mutations. Furthermore, sequences from B-lineage malignant cells nearly reflect the characteristics of the normal counterpart at each respective stage of development. Alternatively, from the IgV region structure of the malignant cells, it is possible to speculate at which stage of B-cell development the cells were transformed. As the complete nucleotide sequences of the human Ig heavy and Ig light V region loci have now been determined, the study of Ig genetics has entered into the super-information era.

  6. Thrombocytopenia in common variable immunodeficiency patients - clinical course, management, and effect of immunoglobulins.

    PubMed

    Pituch-Noworolska, Anna; Siedlar, Maciej; Kowalczyk, Danuta; Szaflarska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2015-01-01

    Common variable immunodeficiency (CVID) is a primary immunodeficiency of humoral immunity with heterogeneous clinical features. Diagnosis of CVID is based on hypogammaglobulinaemia, low production of specific antibodies, and disorders of cellular immunity. The standard therapy includes replacement of specific antibodies with human immunoglobulin, prophylaxis, and symptomatic therapy of infections. High prevalence of autoimmunity is characteristic for CVID, most commonly: thrombocytopaenia and neutropaenia, celiac disease, and systemic autoimmune diseases. The study included seven children diagnosed with CVID and treated with immunoglobulin substitution from 2 to 12 years. Thrombocytopenia was diagnosed prior to CVID in four children, developed during immunoglobulin substitution in three children. In one boy with CVID and thrombocytopaenia, haemolytic anaemia occurred, so a diagnosis of Evans syndrome was established. Therapy of thrombocytopaenia previous to CVID included steroids and/or immunoglobulins in high dose, and azathioprine. In children with CVID on regular immunoglobulin substitution, episodes of acute thrombocytopaenia were associated with infections and were treated with high doses of immunoglobulins and steroids. In two patients only chronic thrombocytopaenia was noted. Splenectomy was necessary in one patient because of severe course of thrombocytopaenia. The results of the study indicated a supportive role of regular immunoglobulin substitution in patients with CVID and chronic thrombocytopaenia. However, regular substitution of immunoglobulins in CVID patients did not prevent the occurrence of autoimmune thrombocytopaenia episodes or exacerbations of chronic form. In episodes of acute thrombocytopaenia or exacerbations of chronic thrombocytopaenia, infusions of immunoglobulins in high dose are effective, despite previous regular substitution in the replacing dose.

  7. Immunoglobulin V/J recombination is accompanied by deletion of joining site and variable region segments.

    PubMed Central

    Seidman, J G; Nau, M M; Norman, B; Kwan, S P; Scharff, M; Leder, P

    1980-01-01

    A site-specific recombination event is responsible for the somatic activation of immunoglobulin genes and for generating a major share of immunoglobulin gene diversity. Although several possible mechanisms can be proposed to account for this process, recombinatio accompanied by deletion is a particularly attractive mechanism because it might utilize inverted repeat sequences noted on the 3' side of all variable regions and on the 5' side of all joining site segments thus far studied. Testing this model is complicated by the fact that antibody cells are at least diploid and gene segments on the inactive chromosome can obscure deletions occurring within the active gene. Accordingly, we have screened several immunoglobulin-producing plasmacytoma lines to select those in which both chromosomes are rearranged. By using appropriate cell lines and variable and joining region probes in in situ hybridization experiments, we show that recombination is accompanied by the deletion of both variable and joining region genes. These experiments also allow us to map the site of V/J recombination of several active immunoglobulin genes and suggest an order and orientation for variable, joining, and constant region sequences. Images PMID:6777777

  8. Immunoglobulin heavy chain variable gene usage and (super)-antigen drive in chronic lymphocytic leukemia.

    PubMed

    Bühler, Andreas; Zenz, Thorsten; Stilgenbauer, Stephan

    2010-01-15

    Increasing evidence supports the prognostic relevance of specific immunoglobulin heavy chain variable (IGHV) genes or stereotyped B-cell receptors (BCR) in chronic lymphocytic leukemia (CLL). The clonotypic BCRs differ in their specificity and affinity toward classical antigens and/or superantigens. The BCR-triggered mechanisms are distinct but could explain in part the different clinical behavior among CLL subgroups.

  9. Subcutaneous immunoglobulin therapy in a patient with myopathic dropped head syndrome and common variable immunodeficiency.

    PubMed

    Rosato, E; Molinaro, I; Pisarri, S; Salsano, F

    2011-01-01

    Prominent neck extension weakness is an uncommon clinical entity, also termed dropped-head syndrome, that may be part of a generalized neuromuscular disorder. We report here the case of a woman with dropped-head syndrome and pulmonary arterial hypertension secondary to systemic sclerosis. Subsequently, she developed common variable immunodeficiency and subcutaneous immunoglobulin therapy was started. After two months from the start of therapy we did not observe any improvement in the degree of flexion of the head, although the clinical examination shows an improvement in neck extensor muscle strength. Subcutaneous immunoglobulin therapy could be a possible therapeutic option for the treatment of myopathic neck extensor weakness.

  10. Coding strategy differences between constant and variable segments of immunoglobulin genes.

    PubMed Central

    Perrin, P

    1984-01-01

    Vertebrate immunoglobulin (Ig) mRNAs reveal intraspecies variation in codon usage distinct from that seen with yeast or bacterial genes. Comparison of all available Ig gene sequences shows that %(G + C) in codon position III is consistently lower in variable (V) segments than in constant (C) segments. I find an even lower %(G + C) in the hypervariable domains of V segments. This analysis suggests that base substitution in Ig genes correlates positively with local A + T content. PMID:6462913

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

    PubMed

    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.

  12. Lymphocytic interstitial pneumonia associated with common variable immunodeficiency resolved with intravenous immunoglobulins.

    PubMed

    Arish, N; Eldor, R; Fellig, Y; Bogot, N; Laxer, U; Izhar, U; Rokach, A

    2006-12-01

    Lymphocytic interstitial pneumonia (LIP) is a rare form of interstitial lung disease. A few case reports have described an association with common variable immunodeficiency (CVID). Corticosteroids are usually used to treat symptomatic patients but their efficacy has never been studied in a controlled trial. We describe a patient with LIP and CVID who was treated monthly with intravenous immunoglobulins (IVIG) without steroids. The patient improved dramatically. We believe that, in selected cases of LIP and immunodeficiency, IVIG given monthly should be considered as the only treatment without adding steroids.

  13. SUBGROUPS OF AMINO ACID SEQUENCES IN THE VARIABLE REGIONS OF IMMUNOGLOBULIN HEAVY CHAINS*

    PubMed Central

    Cunningham, Bruce A.; Pflumm, Mollie N.; User, Urs Rutisha; Edelman, Gerald M.

    1969-01-01

    The amino acid sequence of the first 133 residues of the heavy (γ) chain from a human γG immunoglobulin (He) has been determined. This γ-chain is identical in Gm type to that of protein Eu, the complete sequence of which has been reported. Comparison of the two sequences substantiates the previous suggestion that there are subgroups of variable regions of heavy chains. The variable region of Eu has been assigned to subgroup I and that of He to subgroup II; on the other hand, the constant regions of the two proteins appear to be identical. Comparison of the sequence of the heavy chain of He with the heavy chain sequences determined in other laboratories suggests that the variable region of subgroup II is at least 118 residues long. The nature and distribution of amino acid variations in this heavy chain subgroup resemble those observed in light chain subgroups. These studies provide evidence that the translocation hypothesis applies to heavy as well as to light chains, viz., genes for variable regions (V) are somatically translocated to genes for constant regions (C) to form complete VC structural genes. Images PMID:5264153

  14. Complementarity-determining region 2 is implicated in the binding of staphylococcal protein A to human immunoglobulin VHIII variable regions.

    PubMed

    Randen, I; Potter, K N; Li, Y; Thompson, K M; Pascual, V; Førre, O; Natvig, J B; Capra, J D

    1993-10-01

    Staphylococcal protein A (SPA) has two distinct binding sites on human immunoglobulins. In addition to binding to the Fc region of most IgG molecules, an "alternative" binding site has been localized to the Fab region of human immunoglobulins encoded by heavy chain variable gene segments belonging to the VHIII family. Comparison of amino acid sequences of closely related SPA-binding and -non-binding proteins suggested that VHIII-specific residues in the second complementarity-determining region (CDR2) were likely responsible for SPA binding activity. Site-directed mutagenesis of a single amino acid residue in CDR2 converted an IgM rheumatoid factor which did not bind SPA to an SPA binder. These findings, therefore, locate a critical site involved in SPA binding to the CDR2 of human immunoglobulins encoded by VHIII family gene segments.

  15. 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.

  16. 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

  17. Immunoglobulin variable-region gene mutational lineage tree analysis: application to autoimmune diseases.

    PubMed

    Steiman-Shimony, Avital; Edelman, Hanna; Barak, Michal; Shahaf, Gitit; Dunn-Walters, Deborah; Stott, David I; Abraham, Roshini S; Mehr, Ramit

    2006-04-01

    Lineage trees have frequently been drawn to illustrate diversification, via somatic hypermutation (SHM), of immunoglobulin variable-region (IGV) genes. In order to extract more information from IGV sequences, we developed a novel mathematical method for analyzing the graphical properties of IgV gene lineage trees, allowing quantification of the differences between the dynamics of SHM and antigen-driven selection in different lymphoid tissues, species, and disease situations. Here, we investigated trees generated from published IGV sequence data from B cell clones participating in autoimmune responses in patients with Myasthenia Gravis (MG), Rheumatoid Arthritis (RA), and Sjögren's Syndrome (SS). At present, as no standards exist for cell sampling and sequence extraction methods, data obtained by different research groups from two studies of the same disease often vary considerably. Nevertheless, based on comparisons of data groups within individual studies, we show here that lineage trees from different individual patients are often similar and can be grouped together, as can trees from two different tissues in the same patient, and even from IgG- and IgA-expressing B cell clones. Additionally, lineage trees from most studies reflect the chronic character of autoimmune diseases.

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

    PubMed

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

    1992-08-15

    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.

  19. Levodopa therapy: consequences of the nonphysiologic replacement of dopamine.

    PubMed

    Chase, T N

    1998-05-01

    Normal motor function is dependent on the highly regulated synthesis and release of the transmitter dopamine by neurons projecting from the substantia nigra to the corpus striatum. Parkinson's disease involves the progressive degeneration of these neurons. Its core symptoms are a direct consequence of a striatal insufficiency of intrasynaptic dopamine. Levodopa, the standard of care for the treatment of PD, acts after its conversion to dopamine by restoring striatal dopaminergic transmission. However, there are significant differences between the normally functioning dopamine system and the restoration of function provided by standard levodopa treatment. Increasing clinical and preclinical evidence suggests that the intermittent stimulation of dopamine receptors resulting from current therapeutic regimens contributes to the response complications that ultimately affect most parkinsonian patients. It now appears that chronic nonphysiologic stimulation of dopaminergic receptors on striatal GABAergic neurons activates characteristic signaling pathways, leading to a potentiation of the synaptic efficacy of adjacent glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype. As a result, function of these GABAergic efferent neurons changes in ways that favor the appearance of motor complications. Conceivably, use of dopaminomimetic replacement strategies that provide more continuous dopamine receptor stimulation will act to prevent or alleviate these disabling complications. A number of promising approaches to achieving this goal are now under development.

  20. Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency.

    PubMed

    Borte, Stephan; Pan-Hammarström, Qiang; Liu, Chonghai; Sack, Ulrich; Borte, Michael; Wagner, Ulf; Graf, Dagmar; Hammarström, Lennart

    2009-11-05

    Interleukin-21 (IL-21) is an important promoter for differentiation of human B cells into immunoglobulin (Ig)-secreting cells. The objective of this study was to evaluate an IL-21-based approach to induce immunoglobulin production in B cells from patients with common variable immunodeficiency (CVID) or selective IgA deficiency (IgAD). We show that a combination of IL-21, IL-4, and anti-CD40 stimulation induces class-switch recombination to IgG and IgA and differentiation of Ig-secreting cells, consisting of both surface IgG(+) (sIgG(+)) and sIgA(+) B cells and CD138(+) plasma cells, in patients with CVID or IgAD. Stimulation with IL-21 was far more effective than stimulation with IL-4 or IL-10. Moreover, spontaneous apoptosis of CD19(+) B cells from patients with CVID or IgAD was prevented by a combination of IL-21, IL-4, and anti-CD40 stimulation. Analysis of IL-21 and IL-21 receptor (IL-21R) mRNA expression upon anti-CD3 stimulation of T cells, however, showed no evidence for defective IL-21 expression in CVID patients and sequencing of the coding regions of the IL21 gene did not reveal any mutations, suggesting a regulatory defect. Thus, our work provides an initial basis for a potential therapeutic role of IL-21 to reconstitute immunoglobulin production in CVID and IgAD.

  1. Identification of anti-ErbB2 dual variable domain immunoglobulin (DVD-Ig™) proteins with unique activities.

    PubMed

    Gu, Jinming; Yang, Jinsong; Chang, Qing; Lu, Xiaoqing; Wang, Jieyi; Chen, Mingjiu; Ghayur, Tariq; Gu, Jijie

    2014-01-01

    Inhibiting ErbB2 signaling with monoclonal antibodies (mAbs) or small molecules is an established therapeutic strategy in oncology. We have developed anti-ErbB2 Dual Variable Domain Immunoglobulin (DVD-Ig) proteins that capture the function of a combination of two anti-ErbB2 antibodies. In addition, some of the anti-ErbB2 DVD-Ig proteins gain the new functions of enhancing ErbB2 signaling and cell proliferation in N87 cells. We further found that two DVD-Ig proteins, DVD687 and DVD688, have two distinct mechanisms of actions in Calu-3 and N87 cells. DVD687 enhances cell cycle progression while DVD688 induces apoptosis in N87 cells. Using a half DVD687, we found that avidity may play a key role in the agonist activity of DVD687 in N87 cells.

  2. [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.

  3. A large section of the gene locus encoding human immunoglobulin variable regions of the kappa type is duplicated.

    PubMed

    Pech, M; Smola, H; Pohlenz, H D; Straubinger, B; Gerl, R; Zachau, H G

    1985-06-05

    The structure of a new segment of the gene locus encoding the variable regions of human immunoglobulins of the Kappa type (VK) has been elucidated. This segment (cluster B) encompasses six VK sequences, which belong to three different subgroups and which are arranged in the same transcriptional orientation. Part of cluster B was found to be very similar to another region of the VK gene locus, which was cloned previously (cluster A). Sequence differences between the homologous region of clusters A and B range from 0.2% to 3.7% depending on the position of the VK sequences. The divergence is in the same range for genes and pseudogenes. Hybridization experiments with DNAs from different individuals clearly demonstrate that the two segments are located at different positions within the VK locus and do not represent allelic variants. The sequence homology between clusters A and B is higher than the homology of both clusters to an allelic variant, which is represented by a DNA segment that had been isolated from another individual. These results, together with a report in the literature of two other homologous regions in the VK locus, make it very likely that a major part of even the whole locus is duplicated. In this case, VK gene numbers would be higher than previously estimated on the basis of hybridization studies. An inverse orientation of VK gene clusters would explain published data on rearrangement products in B-cells if an inversion-deletion mechanism is assumed.

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

    PubMed

    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; Jumaa, Hassan

    2015-05-21

    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.

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

    PubMed

    Raut, Ashlesha S; Kalonia, Devendra S

    2016-03-07

    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.

  6. Immunoglobulin variable region hypermutation is associated with a DNA repair deficit

    SciTech Connect

    Valles-Ayoub, Y.; Govan, H.L. III; Braun, J. )

    1991-03-11

    The molecular mechanism of Ig variable region hypermutation is unknown, but has been hypothesized to involve an error-prone DNA repair process. In this study, the authors used a novel PCR-based assay to compare repair of UV-induced DNA damage in mantle zone versus germinal center B lymphocytes. They observed that DNA repair activity within rearranged VDJ loci was sluggish in germinal center B lymphocytes compared to repair activity monitored in mantle zone B lymphocytes. In contrast, DNA repair times within the germline V{sub H}5 gene family, the variable region J{sub H}{endash}C{sub H} intron, and the N-ras gene was rapid and similar in both germinal center and mantle zone B cells. These results reflect a DNA repair deficit which, as expected for hypermutation, is selective for rearranged Ig VDG in germinal center cells. To directly measure the fidelity of DNA repair, the repaired PCR-amplified gene segments were analyzed for sequence changes by restriction enzyme digestion. In experiments thus far, repair of germline V{sub H}5 was error-free in both germinal center and mantle zone B cells. However, while rearranged V{sub H}5 segments were also error-free in mantle zone cells, they were highly mutated in germinal center cells. These findings provide direct biochemical evidence for the role of a sequence- and stage-specific error-prone DNA repair pathway in Ig V gene hypermutation.

  7. Tetrahydromethanopterin-dependent methanogenesis from non-physiological C1 donors in Methanobacterium thermoautotrophicum.

    PubMed Central

    Escalante-Semerena, J C; Wolfe, R S

    1985-01-01

    Methanogenesis from the non-physiological C1 donors thioproline, thiazolidine, hexamethylenetetramine, formaldehyde (HCHO), and HOCH2-S-coenzyme M (CoM) was catalyzed by cell extracts of Methanobacterium thermoautotrophicum under a hydrogen atmosphere. Tetrahydromethanopterin (H4MPT) and HS-CoM were required in the reaction mixture. The non-physiological compounds were found to be in chemical equilibrium with HCHO, which has been shown to react spontaneously with H4MPT to form methylene-H4MPT, an intermediate of the methanogenic pathway at the formaldehyde level of oxidation. Highfield (360 MHZ) 1H and 13C nuclear magnetic resonance studies performed on the interaction between HCHO and HS-CoM showed that these compounds are in equilibrium with HOCH2-S-CoM and that the equilibrium is pH dependent. When methanogenesis from the non-physiological donors was followed under a nitrogen atmosphere, the C1 moiety from each compound underwent a disproportionation, forming methenyl-H4MPT+ and methane. The compounds tested served as substrates for the enzymatic synthesis of methenyl-H4MPT+. PMID:3838170

  8. [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

  9. Gene Expression Profiling in Peripheral Blood Mononuclear Cells of Patients with Common Variable Immunodeficiency: Modulation of Adaptive Immune Response following Intravenous Immunoglobulin Therapy

    PubMed Central

    Barbieri, Alessandro; Tinazzi, Elisa; Rizzi, Monica; Beri, Ruggero; Argentino, Giuseppe; Ottria, Andrea; Lunardi, Claudio; Puccetti, Antonio

    2014-01-01

    Background Regular intravenous immunoglobulin treatment is used to replace antibody deficiency in primary immunodeficiency diseases; however the therapeutic effect seems to be related not only to antibody replacement but also to an active role in the modulation of the immune response. Common variable immunodeficiency is the most frequent primary immunodeficiency seen in clinical practice. Methods We have studied the effect of intravenous immunoglobulin replacement in patients with common variable immunodeficiency by evaluating the gene-expression profiles from Affimetrix HG-U133A. Some of the gene array results were validated by real time RT-PCR and by the measurement of circulating cytokines and chemokines by ELISA. Moreover we performed FACS analysis of blood mononuclear cells from the patients enrolled in the study. Results A series of genes involved in innate and acquired immune responses were markedly up- or down-modulated before therapy. Such genes included CD14, CD36, LEPR, IRF-5, RGS-1, CD38, TNFRSF25, IL-4, CXCR4, CCR3, IL-8. Most of these modulated genes showed an expression similar to that of normal controls after immunoglobulin replacement. Real time RT-PCR of selected genes and serum levels of IL-4, CXCR4 before and after therapy changed accordingly to gene array results. Interestingly, serum levels of IL-8 remained unchanged, as the corresponding gene, before and after treatment. FACS analysis showed a marked decrease of CD8+T cells and an increase of CD4+T cells following treatment. Moreover we observed a marked increase of CD23−CD27−IgM−IgG− B cells (centrocytes). Conclusions Our results are in accordance with previous reports and provide further support to the hypothesis that the benefits of intravenous immunoglobulin therapy are not only related to antibody replacement but also to its ability to modulate the immune response in common variable immunodeficiency. PMID:24831519

  10. 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.

  11. Quantification of Peptides from Immunoglobulin Constant and Variable Regions by Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry for Assessment of Multiple Myeloma Patients

    PubMed Central

    Remily-Wood, Elizabeth R.; Benson, Kaaron; Baz, Rachid C.; Chen, Y. Ann; Hussein, Mohamad; Hartley-Brown, Monique A.; Sprung, Robert W.; Perez, Brianna; Liu, Richard Z.; Yoder, Sean; Teer, Jamie; Eschrich, Steven A.; Koomen, John M.

    2014-01-01

    Purpose Quantitative mass spectrometry assays for immunoglobulins (Igs) are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, e.g. multiple myeloma. Experimental design Using LC-MS/MS data, Ig constant region peptides and transitions were selected for liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM). Quantitative assays were used to assess Igs in serum from 83 patients. Results LC-MRM assays quantify serum levels of Igs and their isoforms (IgG1–4, IgA1–2, IgM, IgD, and IgE, as well as kappa(κ) and lambda(λ) light chains). LC-MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof-of-concept data for defining and monitoring variable region peptides are provided using the H929 multiple myeloma cell line and two MM patients. Conclusions and Clinical Relevance LC-MRM assays targeting constant region peptides determine the type and isoform of the involved immunoglobulin and quantify its expression; the LC-MRM approach has improved sensitivity compared with the current clinical method, but slightly higher interassay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques. PMID:24723328

  12. High rate of somatic point mutation in vitro in and near the variable-region segment of an immunoglobulin heavy chain gene.

    PubMed Central

    Meyer, J; Jäck, H M; Ellis, N; Wabl, M

    1986-01-01

    The "silent" allele at the immunoglobulin heavy-chain locus in the pre-B-lymphocyte line 18-81 contains a correctly assembled gene. However, an amber termination codon within the variable-region gene segment prematurely terminates translation into complete heavy chain. Revertants that do produce heavy chain are generated at a high rate, which is termed hypermutation. By DNA sequencing of subclones, we have confirmed that whenever mu chain is produced by the usually silent allele, a true reversion is found in the DNA. Mutations are not confined to the position of the amber termination codon but are also found at other sites in and near the variable-region gene segment. Images PMID:3092221

  13. Fish Immunoglobulins

    PubMed Central

    Mashoof, Sara; Criscitiello, Michael F.

    2016-01-01

    The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural studies. Work from major aquatic model organisms and less studied comparative species are both included to define what is the rule for an immunoglobulin isotype or taxonomic group and what exemplifies an exception. PMID:27879632

  14. The influence of IgM-enriched immunoglobulin therapy on neonatal mortality and hematological variables in newborn infants with blood culture-proven sepsis.

    PubMed

    Abbasoğlu, Aslıhan; Ecevit, Ayşe; Tuğcu, Ali Ulaş; Yapakçı, Ece; Tekindal, Mustafa Agah; Tarcan, Aylin; Ecevit, Zafer

    2014-01-01

    The aim of this study was to determine the effects of adjuvant immunoglobulin M (IgM)-enriched intravenous immunoglobulin (IVIG) therapy on mortality rate, hematological variables and length of hospital stay in newborn infants with blood culture-proven sepsis. Demographic and clinical features and outcome measures of 63 newborn infants with blood culture-proven sepsis were documented retrospectively from the medical records. The patients were divided into two groups according to their treatment history. The patients in Group 1 received antibiotic therapy only and the patients in Group 2 received both antibiotic and adjuvant IgMenriched IVIG. The study revealed that mortality rates were 28.1% and 12.9% in Group 1 and Group 2, respectively. The mortality rate was lower in Group 2, but the difference between the two groups was not statistically significant (p=0.21). Coagulase-negative Staphylococcus was the most common type of bacteria isolated from the blood culture in both groups. When changing laboratory results were compared between the two groups, hemoglobin, leukocyte count and C-reactive protein levels were different during the first three days of antibiotic treatment. Our study revealed that if diagnosed at an early stage and treated aggressively with appropriate and effective antibiotics, adjuvant IgM-enriched IVIG treatment has no additional benefits in neonatal sepsis.

  15. A reappraisal of immunoglobulin variable gene primers and its impact on assessing clonal relationships between PB B cells and BM plasma cells in AL amyloidosis.

    PubMed

    Katoh, Nagaaki; Poshusta, Tanya L; Manske, Michelle K; Dispenzieri, Angela; Gertz, Morie A; Abraham, Roshini S; Ramirez-Alvarado, Marina

    2011-12-01

    Monoclonal tumor plasma cells as well as non-terminally differentiated B cells having a clonal relationship to the tumor cells have been detected in the peripheral blood (PB) of some multiple myeloma (MM) patients but rarely in light chain (primary systemic) amyloidosis (AL) patients. Previously, our group found these peripheral clonotypic B cells in three AL patients. Here, we report detailed analysis of a larger cohort of AL patients to validate the prior findings and to investigate the effect of this cell population on clinical outcome. Fourteen AL patients were selected from a clinical prospective trial, and the relationship between immunoglobulin light chain variable gene (V(L)) representation in PB B cells and the clonal population in the bone marrow (BM) was investigated. A clonal relationship was not detected, and the present study provides important insights into the disparity with the earlier data, including clinical history of the patients and methodological analysis.

  16. The Florida manatee (Trichechus manatus latirostris) immunoglobulin heavy chain suggests the importance of clan III variable segments in repertoire diversity.

    PubMed

    Breaux, Breanna; Deiss, Thaddeus C; Chen, Patricia L; Cruz-Schneider, Maria Paula; Sena, Leonardo; Hunter, Margaret E; Bonde, Robert K; Criscitiello, Michael F

    2017-01-25

    Manatees are a vulnerable, charismatic sentinel species from the evolutionarily divergent Afrotheria. Manatee health and resistance to infectious disease is of great concern to conservation groups, but little is known about their immune system. To develop manatee-specific tools for monitoring health, we first must have a general knowledge of how the immunoglobulin heavy (IgH) chain locus is organized and transcriptionally expressed. Using the genomic scaffolds of the Florida manatee (Trichechus manatus latirostris), we characterized the potential IgH segmental diversity and constant region isotypic diversity and performed the first Afrotherian repertoire analysis. The Florida manatee has low V(D)J combinatorial diversity (3744 potential combinations) and few constant region isotypes. They also lack clan III V segments, which may have caused reduced VH segment numbers. However, we found productive somatic hypermutation concentrated in the complementarity determining regions. In conclusion, manatees have limited IGHV clan and combinatorial diversity. This suggests that clan III V segments are essential for maintaining IgH locus diversity.

  17. Interaction of 5-fluoro-5'-deoxyuridine with human serum albumin under physiological and non-physiological condition: a biophysical investigation.

    PubMed

    Ishtikhar, Mohd; Rabbani, Gulam; Khan, Rizwan Hasan

    2014-11-01

    Uridine analogs 5'dFUrd (a cytotoxic metabolite of a prodrug capecitabine that enzymatically converted into 5'dFUrd) commonly used in the treatment of advanced human cancers, especially gastrointestinal tract, ovary, colorectal, breast cancers etc. Drugs/metabolites are transported in the blood by transporter proteins like human serum albumin (HSA). Here we investigate the interaction of 5'dFUrd to HSA by spectroscopic and calorimetric techniques at physiological (pH 7.4) and non-physiological (pH 9.0) conditions. The binding constant (Kb), enthalpy change (ΔH°), entropy change (ΔS°) and Gibbs free energy change (ΔG°) were also calculated under both conditions. The secondary structure of HSA showed greater alteration in helicity at physiological pH. ITC measurement reveals that HSA have high binding affinity at physiological pH as compares to non-physiological conditions. The thermostability of HSA alone as well of the HSA-drug complex was found to be higher at physiological pH. The binding study was also explored through molecular docking studies which revealed that 5'dFUrd was bound to subdomain IIA of Sudlow's site I through multiple mode of interaction. These results suggest that 5'dFUrd have high binding affinity at physiological condition or "N" isoform so lower drug concentrations are required in compare to non-physiological or "B" isoform of HSA to completely occupied the binding site of the protein.

  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. Clonal immunoglobulin gene rearrangement in nodular lymphoid hyperplasia of the gastrointestinal tract associated with common variable immunodeficiency.

    PubMed

    Laszewski, M J; Kemp, J D; Goeken, J A; Mitros, F A; Platz, C E; Dick, F R

    1990-09-01

    The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed.

  20. [Cloning and expression of a single human immunoglobulin heavy-chain variable domain with vascular endothelial growth factor binding activity].

    PubMed

    Liu, Heng; Liu, Siguo; Wu, Yi; Zili, M; Liu, Yu; Zhang, Aimin; Chen, Jianquan; Cheng, Guoxiang

    2010-11-01

    In the application of therapeutic antibodies, large molecular weight of antibodies is always a problem that prevents them from penetrating into tissues or binding to antigenic determinants. To overcome this problem, we investigated the function of the heavy chain variable domain of a monoclonal anti-VEGF human IgM antibody derived from the Five-Feature Translocus Mice. We cloned the cDNA of the heavy chain variable domain, which was then inserted into pET28a vector and expressed in Escherichia coli. After purification and renaturation of the denatured recombinant protein, we obtained a 16 kDa antibody fragment, which is named as rhVVH. By immunoassaying its VEGF-binding capability in vitro, we proved that rhVVH retains this activity as the complete IgM. Importantly, rhVVH is shown to inhibit the HUVEC cell proliferation in a concentration-dependent manner. Our results indicate that the single heavy chain variable domain might inherit part of the biological function of the complete IgM antibody, which provided a valuable potential in further research on antibody miniaturisation.

  1. 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

    2015-09-08

    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.

  2. Rapid amplification of cDNA ends (RACE) improves the PCR-based isolation of immunoglobulin variable region genes from murine and human lymphoma cells and cell lines.

    PubMed

    Doenecke, A; Winnacker, E L; Hallek, M

    1997-10-01

    The isolation of rearranged immunoglobulin (Ig) variable region (V) genes is usually performed by PCR with consensus primers binding to conserved regions within the V sequences. However, the isolation of Ig genes by this method is hampered in 15-35% by technical difficulties, mostly mismatches of oligonucleotide primers to V sequences. In order to obtain DNA sequences from V heavy chain (VH) genes which could not be amplified with consensus primers, we used a modified PCR technique, the rapid amplification of cDNA ends (RACE) PCR in combination with new heavy chain constant region primers for the isolation of human and murine VH genes. In comparison, consensus primer PCR with different sets of previously published oligonucleotide primers was used. Both methods were applied to isolate VH genes from murine B cell lymphoma (A20 and BCL1), myeloma (NS1) and hybridoma (SP6) cell lines and from freshly isolated human chronic lymphocytic leukemia and lymphoma cells. RACE PCR allowed the amplification and subsequent cloning of the complete VH gene in all cases. In contrast, consensus primer PCR failed to isolate the VH sequence of the murine A20 cell line; this was explained by a mismatch of consensus primers with VH sequences. When both PCR methods amplified VH sequences, the DNA sequences obtained were identical. Taken together, RACE PCR represents a reliable and versatile method for the isolation of VH genes from human and murine lymphoma cells, in particular if consensus primer PCR fails.

  3. Atypical Antigen Recognition Mode of a Shark Immunoglobulin New Antigen Receptor (IgNAR) Variable Domain Characterized by Humanization and Structural Analysis

    PubMed Central

    Kovalenko, Oleg V.; Olland, Andrea; Piché-Nicholas, Nicole; Godbole, Adarsh; King, Daniel; Svenson, Kristine; Calabro, Valerie; Müller, Mischa R.; Barelle, Caroline J.; Somers, William; Gill, Davinder S.; Mosyak, Lidia; Tchistiakova, Lioudmila

    2013-01-01

    The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable, and specific high affinity monomeric binding proteins of ∼12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, that binds specifically and with high affinity to human, mouse, and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-complementarity-determining region residues to those of a human germ line Vκ1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1) in complex with human serum albumin (HSA) were determined at 3- and 2.3-Å resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to complementarity-determining regions that has not been seen previously in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs. PMID:23632026

  4. Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis.

    PubMed

    Kovalenko, Oleg V; Olland, Andrea; Piché-Nicholas, Nicole; Godbole, Adarsh; King, Daniel; Svenson, Kristine; Calabro, Valerie; Müller, Mischa R; Barelle, Caroline J; Somers, William; Gill, Davinder S; Mosyak, Lidia; Tchistiakova, Lioudmila

    2013-06-14

    The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable, and specific high affinity monomeric binding proteins of ∼12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, that binds specifically and with high affinity to human, mouse, and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-complementarity-determining region residues to those of a human germ line Vκ1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1) in complex with human serum albumin (HSA) were determined at 3- and 2.3-Å resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to complementarity-determining regions that has not been seen previously in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs.

  5. Restricted immunoglobulin variable region gene usage by normal Ly-1 (CD5+) B cells that recognize phosphatidyl choline

    PubMed Central

    1989-01-01

    5-15% of lymphocytes in the peritoneums of normal adult B10.H-2aH- 4bp/Wts (2a4b) mice are CD5+ (Ly-1) B cells that recognize phosphatidyl choline (PtC), a phospholipid component of all mammalian cells. We produced a set of IgM-secreting hybridomas from the peritoneal cells of normal, adult 2a4b mice. We found that this set of hybridomas shows a similarly high frequency of antibodies specific for PtC (21 of 86) that also react with bromelain-treated mouse erythrocytes. Restriction fragment analysis of Ig gene rearrangements and analysis of expressed Ig idiotypes reveal that these cells use a restricted set of variable region genes to generate the PtC-specific antibodies. The Ig genes used by the PtC-specific hybridomas appear to be the same as those found in the PtC-specific Ly-1 B cell lymphomas, CH27 and CH34. PMID:2499651

  6. Conformational flexibility of a human immunoglobulin light chain variable domain by relaxation dispersion nuclear magnetic resonance spectroscopy: implications for protein misfolding and amyloid assembly.

    PubMed

    Mukherjee, Sujoy; Pondaven, Simon P; Jaroniec, Christopher P

    2011-07-05

    The conformational flexibility of a human immunoglobulin κIV light-chain variable domain, LEN, which can undergo conversion to amyloid under destabilizing conditions, was investigated at physiological and acidic pH on a residue-specific basis by multidimensional solution-state nuclear magnetic resonance (NMR) methods. Measurements of backbone chemical shifts and amide (15)N longitudinal and transverse spin relaxation rates and steady-state nuclear Overhauser enhancements indicate that, on the whole, LEN retains its native three-dimensional fold and dimeric state at pH 2 and that the protein backbone exhibits limited fast motions on the picosecond to nanosecond time scale. On the other hand, (15)N Carr--Purcell--Meiboom--Gill (CPMG) relaxation dispersion NMR data show that LEN experiences considerable slower, millisecond time scale dynamics, confined primarily to three contiguous segments of about 5-20 residues and encompassing the N-terminal β-strand and complementarity determining loop regions 2 and 3 in the vicinity of the dimer interface. Quantitative analysis of the CPMG relaxation dispersion data reveals that at physiological pH these slow backbone motions are associated with relatively low excited-state protein conformer populations, in the ~2-4% range. Upon acidification, the minor conformer populations increase significantly, to ~10-15%, with most residues involved in stabilizing interactions across the dimer interface displaying increased flexibility. These findings provide molecular-level insights about partial protein unfolding at low pH and point to the LEN dimer dissociation, initiated by increased conformational flexibility in several well-defined regions, as being one of the important early events leading to amyloid assembly.

  7. Recombination events near the immunoglobulin Cmu gene join variable and constant region genes, switch heavy-chain expression, or inactivate the locus.

    PubMed

    Cory, S; Webb, E; Gough, J; Adams, J M

    1981-04-28

    Immunoglobulin heavy-chain expression is initiated by recombination between a variable region (VH) gene and one of several joining region (JH) genes located near the mu constant region (Cmu) gene, and the active VH gene can subsequently switch to another CH gene. That the general mechanism for CH switching involves recombination between sites within the JH-Cmu intervening sequence and the 5' flanking region of another CH gene is supported here by Southern blot hybridization analysis of eight IgG- and IgA-secreting plasmacytomas. An alternative model requiring successive VH linkage to similar JH clusters near each CH gene is shown to be very unlikely since the mouse genome appears to contain only one complement of the JH locus and no JH gene was detectable within large cloned sequences flanking germline C gamma 3 and C gamma 1 genes. Thus, VH-JH joining and CH switching are mediated by separate regions of "the joining-switch" or J-S element. In each plasmacytoma examined, the J-S element had undergone recombination within both the JH locus and the switch region and was shown to be linked to the functional CH gene in an IgG3, and IgG1, and three IgA secretors. Both JH joining and CH switching occurred by deletion of DNA. Switch recombination occurred at more than one site within the J-S element in different lines, even for recombination with the same CH gene. Significantly, although heavy-chain expression is restricted to one allele ("allelic exclusion"), all rearranged in each plasmacytoma. Some rearrangements were aberrant, involving, for example, deletion of all JH genes from the allele. Hence, an error-prone recombination machinery may account for allelic exclusion in many plasmacytomas.

  8. Characterization of antibodies directed against the immunoglobulin light kappa chain variable chain region (VK) of hepatitis C virus-related type-II mixed cryoglobulinemia and B-cell proliferations.

    PubMed

    de Re, Valli; Simula, Maria Paola; Pavan, Alessandro; Garziera, Marica; Marin, Dolores; Dolcetti, Riccardo; de Vita, Salvatore; Sansonno, Domenico; Geremia, Silvano; Toffoli, Giuseppe

    2009-09-01

    Autoimmune type-II cryoglobulinemia (II-MC) is sustained by hepatitis C virus (HCV) infection and B-cell (oligo)clones. This is the reason why the disease may be considered an "indolent B-cell lymphoma (NHL)." B clones show a restricted use of immunoglobulin variable genes (BCR), in particular in the use of the variable kappa (VK)3-20/15 light chain, and show a homology between their BCR functional regions and those of autoimmune rheumatoid factors. We underlined the BCR unique repertoire with frequent rheumatoid factor activity also observed in other autoimmune disorders associated with NHL. The immunoglobulin idiotype is a clonal B-cell marker and an ideal target for immunotherapy. Five monoclonal antibodies were produced in our laboratory toward the VK3-20 of a subject with HCV infection and a II-MC-associated NHL. Epitope determination was performed using the epitope excision approach. Monoclonal antibody reactivity was tested in vitro in ELISA, Western blot, and cytofluorimetry. Data confirmed that a panel of antibodies, reactive against shared idiotypes, can be produced from patients with HCV-associated B-cell lymphoproliferative diseases, thus obviating the need to produce an anti-idiotype antibody for each patient.

  9. Quantitative immunoglobulins in adulthood.

    PubMed

    Crisp, Howard C; Quinn, James M

    2009-01-01

    Although age-related changes in serum immunoglobulins are well described in childhood, alterations in immunoglobulins in the elderly are less well described and published. This study was designed to better define expected immunoglobulin ranges and differences in adults of differing decades of life. Sera from 404 patients, aged 20-89 years old were analyzed for quantitative immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA). The patients with diagnoses or medications known to affect immunoglobulin levels were identified while blinded to their immunoglobulin levels. A two-factor ANOVA was performed using decade of life and gender on both the entire sample population as well as the subset without any disease or medication expected to alter immunoglobulin levels. A literature review was also performed on all English language articles evaluating quantitative immunoglobulin levels in adults >60 years old. For the entire population, IgM was found to be higher in women when compared with men (p < 0.001) and lower in the oldest sample population compared with the youngest population (p < 0.001). For the population without diseases known to affect immunoglobulin levels, the differences in IgM with gender and age were maintained (p < or = 0.001) and IgA levels were generally higher in the older population when compared with the younger population (p = 0.009). Elderly patients without disease known to affect immunoglobulin levels have higher serum IgA levels and lower serum IgM levels. Women have higher IgM levels than men throughout life. IgG levels are not significantly altered in an older population.

  10. 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

  11. Thermodynamic stability contributes to immunoglobulin specificity.

    PubMed

    Dimitrov, Jordan D; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien

    2014-05-01

    Antigen-binding specificity of immunoglobulins is important for their function in immune defense. However, immune repertoires contain a considerable fraction of immunoglobulins with promiscuous binding behavior, the physicochemical basis of which is not well understood. Evolution of immunoglobulin specificity occurs through iterative processes of mutation and selection, referred to as affinity maturation. Recent studies reveal that some somatic mutations could compromise the thermodynamic stability of the variable regions of immunoglobulins. By integrating this observation with the wealth of data on the evolution of novel enzyme activities, we propose that antibody specificity is linked to the thermodynamic stability of the antigen-binding regions, which provides a quantitative distinction between highly specific and promiscuous antibodies.

  12. 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.

  13. 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.

  14. Immunoglobulin treatment in primary antibody deficiency.

    PubMed

    Maarschalk-Ellerbroek, L J; Hoepelman, I M; Ellerbroek, P M

    2011-05-01

    The primary antibody deficiency syndromes are characterised by recurrent respiratory tract infections and the inability to produce effective immunoglobulin (Ig) responses. The best-known primary antibody deficiencies are common variable immunodeficiency (CVID), X-linked agammaglobulinaemia (XLA), immunoglobulin G (IgG) subclass deficiency, and selective antibody deficiency with normal immunoglobulins (SADNI). Therapy in these patients consists of prophylactic antibiotics and/or Ig replacement therapy. Diagnostic delay remains common owing to limited awareness of the presenting features and may result in increased morbidity and mortality. Replacement therapy with immunoglobulins increases life expectancy and reduces the frequency and severity of infections, but the effect on end-organ damage is still unknown. Both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) treatment appear to be safe, with comparable efficacy. A starting dose of 300-400 mg/kg/month in IVIg and 100 mg/week for SCIg is recommended. IgG trough levels should be >5 g/L for patients with agammaglobulinaemia and 3 g/L greater than the initial IgG level for patients with CVID; however, the clinical response should be foremost in choosing the dose and trough level. Infusion-related adverse reactions are generally mild owing to improved manufacturing processes. In this paper, aspects of Ig replacement therapy in primary antibody-deficient patients will be addressed.

  15. 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

  16. 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.

  17. 6th International Immunoglobulin Symposium: poster presentations.

    PubMed

    Fernandez-Cruz, E; Kaveri, S V; Peter, H-H; Durandy, A; Cantoni, N; Quinti, I; Sorensen, R; Bussel, J B; Danieli, M G; Winkelmann, A; Bayry, J; Käsermann, F; Späth, P; Helbert, M; Salama, A; van Schaik, I N; Yuki, N

    2009-12-01

    The posters presented at the 6th International Immunoglobulin Symposium covered a wide range of fields and included both basic science and clinical research. From the abstracts accepted for poster presentation, 12 abstracts were selected for oral presentations in three parallel sessions on immunodeficiencies, autoimmunity and basic research. The immunodeficiency presentations dealt with novel, rare class-switch recombination (CSR) deficiencies, attenuation of adverse events following IVIg treatment, association of immunoglobulin (Ig)G trough levels and protection against acute infection in patients with X-linked agammaglobulinaemia (XLA) and common variable immunodeficiency (CVID), and the reduction of class-switched memory B cells in patients with specific antibody deficiency (SAD). The impact of intravenous immunoglobulin on fetal alloimmune thrombocytopenia, pregnancy and postpartum-related relapses in multiple sclerosis and refractory myositis, as well as experiences with subcutaneous immunoglobulin in patients with multi-focal motor neuropathy, were the topics presented in the autoimmunity session. The interaction of dendritic cell (DC)-SIGN and alpha2,6-sialylated IgG Fc and its impact on human DCs, the enrichment of sialylated IgG in plasma-derived IgG, as wells as prion surveillance and monitoring of anti-measles titres in immunoglobulin products, were covered in the basic science session. In summary, the presentations illustrated the breadth of immunoglobulin therapy usage and highlighted the progress that is being made in diverse areas of basic and clinical research, extending our understanding of the mechanisms of immunoglobulin action and contributing to improved patient care.

  18. Immunoglobulin in intestinal secretions.

    PubMed

    Cutropia de Guirao, C

    1977-12-01

    The objective of the present investigation is the study and interpretation of the role played by the immunoglobulins, especially IgA, during acute diarrhea in children. IgA, IGG and IgM values in serum and IgA in intestinal secretions were studied in a group of children (between 3 months and 5 years of age) during diarrhea, convalescence and in normals. The method of simple radial immunodiffusion according to Mancini was employed. IgA is the immunoglobulin which suffers the greastest alteration in acute diarrhea. The precipitation halos (the average values), were lower during the diarrhea than in convalescence and in normals.

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

    PubMed

    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.

  20. Recombinant immunoglobulin variable domains generated from synthetic genes provide a system for in vitro characterization of light-chain amyloid proteins.

    PubMed Central

    Stevens, P. W.; Raffen, R.; Hanson, D. K.; Deng, Y. L.; Berrios-Hammond, M.; Westholm, F. A.; Murphy, C.; Eulitz, M.; Wetzel, R.; Solomon, A.

    1995-01-01

    The primary structural features that render human monoclonal light chains amyloidogenic are presently unknown. To gain further insight into the physical and biochemical factors that result in the pathologic deposition of these proteins as amyloid fibrils, we have selected for detailed study three closely homologous protein products of the light-chain variable-region single-gene family VkIV. Two of these proteins, REC and SMA, formed amyloid fibrils in vivo. The third protein, LEN, was excreted by the patient at levels of 50 g/day with no indication of amyloid deposits. Sequences of amyloidogenic proteins REC and SMA differed from the sequence of the nonpathogenic protein LEN at 14 and 8 amino acid positions, respectively, and these amino acid differences have been analyzed in terms of the three-dimensional structure of the LEN dimer. To provide a replenishable source of these human proteins, we constructed synthetic genes coding for the REC, SMA, and LEN variable domains and expressed these genes in Escherichia coli. Immunochemical and biophysical comparisons demonstrated that the recombinant VkIV products have tertiary structural features comparable to those of the patient-derived proteins. This well-defined set of three clinically characterized human kIV light chains, together with the capability to produce these kIV proteins recombinantly, provide a system for biophysical and structural comparisons of two different amyloidogenic light-chain proteins and a nonamyloidogenic protein of the same subgroup. This work lays the foundation for future investigations of the structural basis of light-chain amyloidogenicity. PMID:7795526

  1. Linear immunoglobulin A bullous dermatosis.

    PubMed

    Fortuna, Giulio; Marinkovich, M Peter

    2012-01-01

    Linear immunoglobulin A (IgA) bullous dermatosis, also known as linear IgA disease, is an autoimmune mucocutaneous disorder characterized by subepithelial bullae, with IgA autoantibodies directed against several different antigens in the basement membrane zone. Its immunopathologic characteristic resides in the presence of a continuous linear IgA deposit along the basement membrane zone, which is clearly visible on direct immunofluorescence. This disorder shows different clinical features and distribution when adult-onset of linear IgA disease is compared with childhood-onset. Diagnosis is achieved via clinical, histopathologic, and immunopathologic examinations. Two common therapies are dapsone and sulfapyridine, which reduce the inflammatory response and achieve disease remission in a variable period of time.

  2. Structure and function of immunoglobulins.

    PubMed

    Schroeder, Harry W; Cavacini, Lisa

    2010-02-01

    Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2.

  3. [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.

  4. 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.

  5. Production and Characterization of a Set of Mouse-Human Chimeric Immunoglobulin G (IgG) Subclass and IgA Monoclonal Antibodies with Identical Variable Regions Specific for Pseudomonas aeruginosa Serogroup O6 Lipopolysaccharide

    PubMed Central

    Preston, Michael J.; Gerçeker, A. Alev; Reff, Mitchell E.; Pier, Gerald B.

    1998-01-01

    The heavy- and light-chain variable regions from a murine monoclonal antibody that recognize Pseudomonas aeruginosa serogroup O6 lipopolysaccharide (LPS) were used to generate a series of chimeric mouse-human monoclonal antibodies with identical variable regions. The murine variable-region gene segments were cloned into an immunoglobulin (Ig) cDNA expression vector that contained the human kappa light-chain and IgG1 constant regions. The IgG1 heavy-chain constant region was then replaced with the human IgG2, IgG3, IgG4, or IgA1 heavy-chain constant region. The five different expression vectors were transfected into Chinese hamster ovary cells for antibody production. The chimeric antibodies exhibited immunoreactivity and affinity similar to that of the parental murine IgG antibody toward whole cells of a serogroup O6 strain. In vitro complement deposition assays demonstrated that the chimeric IgG4 and IgA antibodies did not mediate the deposition of complement component C3 onto the surface of either purified LPS or whole bacteria. The chimeric IgG1 and IgG3 antibodies were similar in their ability to deposit C3 onto the surface of both bacteria and LPS, while IgG2 antibody was more effective at depositing C3 onto the surface of bacteria than onto purified LPS. The pattern of opsonophagocytic activity of the chimeric monoclonal antibodies was similar to that of complement deposition onto bacterial cells in that the chimeric IgG1 and IgG3 had the highest opsonic activity. Although IgG2 deposited more C3 onto the bacterial surface than did IgG4 or IgA, all three of these isotypes had low opsonic activity against the serogroup O6 target strain. This series of related antibodies will help reveal functional differences in efficacy among protective antibodies to P. aeruginosa and will be critical for defining the optimal formulation of either a vaccine for active immunization or a polyclonal intravenous IgG or monoclonal antibody cocktail for passive immunotherapy. PMID

  6. Generation and characterization of ABBV642, a dual variable domain immunoglobulin molecule (DVD-Ig) that potently neutralizes VEGF and PDGF-BB and is designed for the treatment of exudative age-related macular degeneration.

    PubMed

    Ding, Kun; Eaton, Lucia; Bowley, Diana; Rieser, Matthew; Chang, Qing; Harris, Maria C; Clabbers, Anca; Dong, Feng; Shen, Jikui; Hackett, Sean F; Touw, Debra S; Bixby, Jacqueline; Zhong, Suju; Benatuil, Lorenzo; Bose, Sahana; Grinnell, Christine; Preston, Gregory M; Iyer, Ramesh; Sadhukhan, Ramkrishna; Marchie, Susan; Overmeyer, Gary; Ghayur, Tariq; van Riet, Deborah A; Tang, Shibo; Campochario, Peter A; Gu, Jijie

    Exudative age-related macular degeneration (AMD) is the most common cause of moderate and severe vision loss in developed countries. Intraocular injections of vascular endothelial growth factor (VEGF or VEGF-A)-neutralizing proteins provide substantial benefit, but frequent, long-term injections are needed. In addition, many patients experience initial visual gains that are ultimately lost due to subretinal fibrosis. Preclinical studies and early phase clinical trials suggest that combined suppression of VEGF and platelet-derived growth factor-BB (PDGF-BB) provides better outcomes than suppression of VEGF alone, due to more frequent regression of neovascularization (NV) and suppression of subretinal fibrosis. We generated a dual variable domain immunoglobulin molecule, ABBV642 that specifically and potently binds and neutralizes VEGF and PDGF-BB. ABBV642 has been optimized for treatment of exudative AMD based on the following design characteristics: 1) high affinity binding to all VEGF-A isoforms and both soluble and extracellular matrix (ECM)-associated PDGF-BB; 2) potential for extended residence time in the vitreous cavity to decrease the frequency of intraocular injections; 3) rapid clearance from systemic circulation compared with molecules with wild type Fc region for normal FcRn binding, which may reduce the risk of systemic complications; and 4) low risk of potential effector function. The bispecificity of ABBV642 allows for a single injection of a single therapeutic agent, and thus a more streamlined development and regulatory path compared with combination products. In a mouse model of exudative AMD, ABBV642 was observed to be more effective than aflibercept. ABBV642 has potential to improve efficacy with reduced injection frequency in patients with exudative AMD, thereby reducing the enormous disease burden for patients and society.

  7. The discovery of immunoglobulin E.

    PubMed

    Ribatti, Domenico

    2016-03-01

    The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE.

  8. [Blood serum immunoglobulins in thyrotoxicosis].

    PubMed

    Epishin, A V

    1978-01-01

    Serum immunoglobulin content was determined in 85 patients with thyrotoxicosis and in 80 healthy persons by radial immunodiffusion in agar after Mancini by means of monospecific antisera (made at the N. F. Gamaleya Institute of Epidemiology immunoglobulins of classes G and M. The most pronounced increase was noted in patients with severe and moderate thyrotoxicosis.

  9. A new high molecular weight immunoglobulin class from the carcharhine shark: implications for the properties of the primordial immunoglobulin.

    PubMed Central

    Berstein, R M; Schluter, S F; Shen, S; Marchalonis, J J

    1996-01-01

    All immunoglobulins and T-cell receptors throughout phylogeny share regions of highly conserved amino acid sequence. To identify possible primitive immunoglobulins and immunoglobulin-like molecules, we utilized 3' RACE (rapid amplification of cDNA ends) and a highly conserved constant region consensus amino acid sequence to isolate a new immunoglobulin class from the sandbar shark Carcharhinus plumbeus. The immunoglobulin, termed IgW, in its secreted form consists of 782 amino acids and is expressed in both the thymus and the spleen. The molecule overall most closely resembles mu chains of the skate and human and a new putative antigen binding molecule isolated from the nurse shark (NAR). The full-length IgW chain has a variable region resembling human and shark heavy-chain (VH) sequences and a novel joining segment containing the WGXGT motif characteristic of H chains. However, unlike any other H-chain-type molecule, it contains six constant (C) domains. The first C domain contains the cysteine residue characteristic of C mu1 that would allow dimerization with a light (L) chain. The fourth and sixth domains also contain comparable cysteines that would enable dimerization with other H chains or homodimerization. Comparison of the sequences of IgW V and C domains shows homology greater than that found in comparisons among VH and C mu or VL, or CL thereby suggesting that IgW may retain features of the primordial immunoglobulin in evolution. Images Fig. 1 Fig. 3 PMID:8622930

  10. Immunoglobulin levels of vitiligo patients.

    PubMed

    Ali, Rubaiya; Ahsan, Mohammad Shamsul; Azad, Mohammad Abul Kalam; Ullah, Md Ashik; Bari, Wasimul; Islam, Sheikh Nazrul; Yeasmin, Sabina; Hasnat, Abul

    2010-01-01

    In the present study, the serum immunoglobulin profiles of vitiligo patients were compared with that of cohort control and evaluated the correlation between immunoglobulin level with their socioeconomic factors and nutritional status. Thirty vitiligo patients were recruited randomly from the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University Hospital, Dhaka, Bangladesh for this study. Thirty healthy individuals as control group matched by age, sex, education and socioeconomic factors to the patient group were selected. Serum immunoglobulin concentrations were determined by turbidimetry method using immunoglobulin kit. The concentration of IgG and IgA decreased significantly (P<0.05), but the change of IgM was not significant. Socioeconomic data revealed that most of the patients were young and female. Moreover statistical analysis revealed that there was significant correlation between immunoglobulin (IgG and IgA only) concentrations and BMI and number of depigmented patches with IgG concentrations. Finally it can be concluded that the change of serum immunoglobulin concentration in vitiligo patients could be due to the disease condition as pathomechanism suggested the aberrations in cellular immunity. But study with larger number of population is required for further evaluation of the relationship between the immune response and disease state to confirm these findings.

  11. [Subcutaneous immunoglobulin substitution and therapy].

    PubMed

    Gulácsy, Vera; Maródi, László

    2011-01-09

    Patients with combined primary immunodeficiency or B-cell deficiency with low serum concentration of immunoglobulin G can be efficiently treated with immunoglobulin G concentrates. From the 1950s IgG was used intramuscularly, and from the 1980s intravenous immunoglobulin (IVIG) replacement has become widely available for replacement therapy. Among the potential side effects of IVIG (including anaphylaxis), further disadvantages of IVIG are hospitalization during treatment and varying concentrations of IgG. Over the past ten years, subcutaneous IgG (SCIG) preparations have become reasonable alternatives to IVIG. SCIG given weekly assures a more balanced serum IgG level, side affects are mostly local and temporary; systemic, severe adverse events have not been observed. In addition, SCIG can be used for home treatment of patients which improves their quality of life remarkably.

  12. Serum immunoglobulins in Nigerian neonates.

    PubMed

    Akinwolere, O A; Akinkugbe, F M; Oyewole, A I; Salimonu, L S

    1989-01-01

    Serum immunoglobulins G, M and A levels were studied in 187 Nigerian neonates. Estimations were done by the radial immunodifusion method of Mancini. Immunoglobulin G shows a fall in value in the first few days of life to about 62% of the value in the last days of the neonatal period. There is however a gradual increase in the level of IgM to about double at the end of the neonatal period. IgA level remained relatively constantly low throughout this period. The effect of maternal education on the levels of immunoglobulins of their neonates was also investigated. This had a positive influence at the secondary educational level, affecting only the IgG and IgA.

  13. 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.

  14. Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila.

    PubMed Central

    Byrd, T F; Horwitz, M A

    1991-01-01

    We have been exploring the role of iron in the pathogenesis of the intracellular bacterial pathogen Legionella pneumophila. In previous studies, we have demonstrated that L. pneumophila intracellular multiplication in human monocytes is iron dependent and that IFN gamma-activated monocytes inhibit L. pneumophila intracellular multiplication by limiting the availability of iron. In this study, we have investigated the effect on L. pneumophila intracellular multiplication of lactoferrin, an iron-binding protein which is internalized via specific receptors on monocytes, and of nonphysiologic iron chelates which enter monocytes by a receptor-independent route. Apolactoferrin completely inhibited L. pneumophila multiplication in nonactivated monocytes, and enhanced the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication. In contrast, iron-saturated lactoferrin had no effect on the already rapid rate of L. pneumophila multiplication in nonactivated monocytes. Moreover, it reversed the capacity of activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron from the lactoferrin-lactoferrin receptor pathway. The capacity of iron-lactoferrin to reverse monocyte activation was dependent upon its percent iron saturation and not just its total iron content. Similarly, the nonphysiologic iron chelates ferric nitrilotriacetate and ferric ammonium citrate completely reverse and ferric pyrophosphate partially reversed the capacity of IFN gamma-activated monocytes to inhibit L. pneumophila intracellular multiplication, demonstrating that L. pneumophila can utilize iron derived from nonphysiologic iron chelates internalized by monocytes independently of the transferrin and lactoferrin endocytic pathways. This study suggests that at sites of inflammation, lactoferrin may inhibit or promote L. pneumophila intracellular multiplication in mononuclear phagocytes depending upon

  15. 7th International Immunoglobulin Conference: Immunodeficiencies

    PubMed Central

    Schmidt, R E; Ochs, H D

    2014-01-01

    Awareness of the challenges involved in diagnosing and treating a heterogeneous group of immunodeficiency disorders is growing. The improvements in neonatal screening offer new methods to ensure that primary immunodeficiencies (PIDs) are diagnosed as early as possible, enabling accurate treatment and the prevention of life-threatening infections and other complications. Additionally, the need to individualize patient therapy in order to optimize both clinical outcomes and quality-of-life is obvious and is exemplified by the ability to switch between intravenous and subcutaneous immunoglobulin administration offering flexible treatment regimens. However, further research is crucial in order to determine the optimal treatment for secondary immunodeficiencies, and to gain greater understanding of the underlying causes of PIDs, including common variable immunodeficiency. The information relating to the growth of patient registries is encouraging, with approximately 25 000 patients with PIDs included in the two registries discussed. Registries such as this are vital for future research, as well as providing an educational resource. PMID:25546748

  16. Structural repertoire of immunoglobulin λ light chains.

    PubMed

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-05-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition.

  17. The interactions of calreticulin with immunoglobulin G and immunoglobulin Y.

    PubMed

    Møllegaard, Karen Mai; Duus, Karen; Træholt, Sofie Dietz; Thaysen-Andersen, Morten; Liu, Yan; Palma, Angelina S; Feizi, Ten; Hansen, Paul R; Højrup, Peter; Houen, Gunnar

    2011-07-01

    Calreticulin is a chaperone of the endoplasmic reticulum (ER) assisting proteins in achieving the correctly folded structure. Details of the binding specificity of calreticulin are still a matter of debate. Calreticulin has been described as an oligosaccharide-binding chaperone but data are also accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin. The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins. Additionally, calreticulin peptide binding was examined with synthetic peptides covering the IgG Cγ2 domain demonstrating interaction with approximately half the peptides. Our results show that the dominant binding activity of calreticulin in vitro is toward the polypeptide moieties of IgG and IgY even in the presence of the monoglucosylated high mannose N-linked oligosaccharide on IgY.

  18. Proteolysis of lymphocytic surface immunoglobulin.

    PubMed Central

    Hough, D W; McIlroy, B M; Stevenson, G T

    1977-01-01

    Limited proteolysis of lymphocytic surface immunoglobulins in guinea-pig, rabbit and man was investigated by immunofluorescence using conjugated antisera specific for immunoglobulin fragments. The cell surface IgM of guinea pig L2C leukaemic lymphocytes and rabbit blood lymphocytes was cleaved in situ at its hinge region by papain. The Fcmicron fragment remained attached to the membrane and could be stained with the appropriate anti-Fc conjugate. The surface IgD and IgM of human chronic lymphocytic leukaemia cells was cleared from the cell surface by papain, as shown by reagents directed against both Fab and Fc region determinants. This could be due either to proteolytic degradation of membrane bound Fc or to initial cleavage of Ig from the membrane at some point other than the hinge region. PMID:321347

  19. 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.

  20. Faecal eosinophil cationic protein and serum immunoglobulin E in relation to infant feeding practices.

    PubMed

    Hua, Man-Chin; Chen, Chien-Chang; Liao, Sui-Ling; Yao, Tsung-Chieh; Tsai, Ming-Han; Lai, Shen-Hao; Chiu, Chih-Yung; Yeh, Kuo-Wei; Huang, Jing-Long

    2017-03-01

    Background To date, the effects of exclusive breastfeeding duration and timing of solid food introduction on allergy prevention are unclear. The aim of this study was to determine the effect of variable feeding practices on intestinal inflammation in infants using faecal eosinophil cationic protein as a surrogate marker and to assess whether faecal eosinophil cationic protein is associated with serum immunoglobulin E. Methods Subjects ( n = 206) were enrolled from the Prediction of Allergies in Taiwanese CHildren (PATCH) birth cohort study. Stool samples were collected at 6 and 12 months for determining eosinophil cationic protein, and blood was collected for determining total and allergen-specific immunoglobulin E at 12 months. We compared these biomarkers between infants with variable exclusive breastfeeding duration and infants introduced to solid foods at various periods. The association between faecal eosinophil cationic protein, total serum immunoglobulin E and specific immunoglobulin E was also analysed. Results Faecal eosinophil cationic protein was significantly higher in exclusively breastfed infants compared with formula-fed infants and infants who were not exclusively breastfed at 6 months of age ( P < 0.05). At 12 months, infants who were introduced to solid foods at 5-6 months had the lowest faecal eosinophil cationic protein compared with those who were introduced at earlier and later periods. There was no significant association between faecal eosinophil cationic protein and serum immunoglobulin E. Conclusion We found that breastfeeding exclusively for >6 months did not reduce serum immunoglobulin E, but rather increased intestinal inflammation. Faecal eosinophil cationic protein was not associated with total serum immunoglobulin E and specific immunoglobulin E and might not be a useful indictor of immunoglobulin E sensitization in infancy.

  1. 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

  2. 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.

  3. The vectorial release of nascent immunoglobulin peptides

    PubMed Central

    Bevan, Michael J.

    1971-01-01

    A microsomal preparation from a mouse plasmacytoma, MOPC 47A, that secretes immunoglobulin A was used to study the release of nascent immunoglobulin peptides in vitro. Nascent chains were released with puromycin and characterized with specific antiserum against the immunoglobulin product of the tumour. When the tissue had been prelabelled with [3H]leucine the experiments were complicated by the large background of completed radioactive polypeptides in the microsomal preparation. Up to one-third of the released radioactivity in the microsomal preparation could be recognized as immunoglobulin. With [3H]-puromycin as the radioactive label, however, the results are much easier to interpret, although the proportion of released radioactivity that can be identified as immunoglobulin is lower (up to one-tenth). Both types of experiment demonstrate that all of the recognizable nascent immunoglobulin chains remain in association with the microsomal vesicles after release from the ribosomes. PMID:5124814

  4. The T-cell receptor as immunoglobulin: paradigm regained.

    PubMed

    Marchalonis, J J; Schluter, S F; Edmundson, A B

    1997-12-01

    The quest to determine the molecular nature of T-lymphocyte receptors for antigen was a "holy grail" to immunologists for over 25 years. This paper updates a review written 15 years ago (Marchalonis JJ, Hunt JC. Proc Soc Exp Biol Med 171:127-145, 1982), which proposed that "these molecules apparently do not bear determinants specified by the major histocompatibility complex, but express Ig-related variable regions and constant regions unique to T-cell products." We review subsequent contributions from molecular biology, protein chemistry, peptide immunochemistry, and structural biology establishing that T-cell receptors (TCRs) are members of the immunoglobulin family restricted to T cells that share 3-dimensional structural features, sequence homology, antigenic cross-reactivity, and common mechanisms of diversification with conventional immunoglobulins. These molecules and their light- and heavy-chain siblings appeared contemporaneously in vertebrate evolution with the emergence of sharks. We illustrate how extrapolation of concepts from immunoglobulin to T-cell receptors has aided in the understanding of these often enigmatic molecules, and, conversely, how concepts derived for T-cell receptors such as the role of "superantigens" can be directly applied to conventional immunoglobulins. A second precept that follows from the symmetry of the combining sites of Igs and TCRs is that MHC-restricted antibodies should exist. Such molecules have in fact been reported, and the x-ray crystallography for T-cell receptors suggests that the combining sites recognizing simultaneously MHC and peptide epitopes resemble the combining sites of antibodies directed against protein determinants. Additional immunoglobulin molecules of nonmammalian species have been detected and characterized based upon conserved homology to TCR and Igs, and it is anticipated that further study will enable the identification of more antigen-specific members of the family in mammals as well.

  5. 7th International Immunoglobulin Conference: Immunoglobulin in clinical practice.

    PubMed

    Shapiro, R S; Borte, M

    2014-12-01

    Intravenous and subcutaneous immunoglobulins (IVIg and SCIg, respectively) are increasingly used in clinical practice, not only as replacement therapy but also for immunomodulation. Physicians have learned that primary immunodeficiency (PID) patients are susceptible to recurrent respiratory tract infections even when appropriately treated with immunoglobulin (Ig) therapy. Further investigation will establish whether a combined therapeutic approach including Ig dose optimization will prevent progressive lung disease in PID. The wear-off effects observed with IVIg can be minimized by adjusting the dosing regimen. It is also possible to avoid the cyclic wear-off following transition to SCIg administration. Consideration of benefit versus risk with Ig therapy includes evaluating the potential occurrence of thromboembolic and haemolytic events, which may be more frequent when Ig is administered in high doses and in the presence of pre-existing risk factors. The ability to select an administration method from IVIg, SCIg or hyaluronidase-facilitated SCIg infusions provides patient choice and alternatives if one or other administration route is not suitable for a patient. The evolution in indications, applications, and understanding of Ig therapy described here has reinforced the need for robust methods to prioritize Ig use.

  6. Immunoglobulins in human aqueous humour.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Saha, K.

    1977-01-01

    The immunoglobulin concentrations in human aqueous humour from 44 patients aged 35 to 85 years with cataracts were measured by a standard immunodiffusion method. IgG was found in all the samples (mean level 7-0 mg/100 ml. IgD, IgA or IgM could not be detected. There was no significant difference in IgG levels in aqueous humour between the two sexes, in different age groups, and in the different types of cataracts. PMID:403928

  7. The immunoglobulin heavy chain locus in the reptile Anolis carolinensis.

    PubMed

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

    2009-05-01

    We describe the entire immunoglobulin heavy chain (IgH) locus from the reptile Anolis carolinensis. The heavy chain constant (C(H)) region includes C mu, C delta and C upsilon genes. This is the first description of a C upsilon gene in the reptilian class. Variable (V(H)), diversity (D(H)) and joining (J(H)) genes are located 5' from the constant (C(H)) chain complex locus. The C mu and C upsilon genes encode antibodies with four immunoglobulin domains. The C delta gene encoded an 11 domain delta heavy chain as in Eublepharis macularius. Seventy V(H) genes, belonging to 28 families, were identified, and they can be sorted into five broader groups. The similarity of the organization of the reptilian genes with those of amphibians and mammals suggests the existence of a process of heavy chain genomic reorganization before the radiation of tetrapod vertebrates.

  8. Blood Test: Immunoglobulin A (IgA)

    MedlinePlus

    ... to 2-Year-Old Blood Test: Immunoglobulin A (IgA) KidsHealth > For Parents > Blood Test: Immunoglobulin A (IgA) Print A A A What's in this article? ... Questions en español Análisis de sangre: inmunoglobulina A (IgA) What It Is An IgA test measures the ...

  9. Pharmacoeconomics of immunoglobulins in primary immunodeficiency.

    PubMed

    Simoens, Steven

    2009-08-01

    Primary immunodeficiency disorders are associated with increased patient susceptibility to recurrent infections. Since the 1950s, intramuscular, intravenous and subcutaneous immunoglobulin products have been used to replace functionally deficient or absent immunoglobulins, reduce the incidence of infections and prevent organ damage caused by infections. This article aims to review the use of immunoglobulin therapy in primary immunodeficiency by focusing on costs, effectiveness, cost-effectiveness, supply and off-label use. To date, the economic burden of primary immunodeficiency is unknown. Past studies have supported minimal differences in effectiveness between intravenous and subcutaneous immunoglobulins. Subcutaneous therapy may be considered for patients who prefer treatment at home. The small number of economic evaluations and their methodological limitations precludes the recommendation of a specific product for use in primary immunodeficiency on pharmacoeconomic grounds. Demand for immunoglobulins has increased over time, leading to periodic shortages and emphasizing the importance of its appropriate use.

  10. [Serum immunoglobulin E level in bronchial asthma].

    PubMed

    Denchev, K; Radkov, M; Lipcheva, N

    1976-01-01

    Serum immunoglobulin E level was determined in 50 patients with bronchial asthma, treated in the out-patients department and clinical conditions at the Faculty Hospital--Varna. The quantitative determination of immunoglobulin E was carried out by radial immunodiffusion according to Mancini with monospecific anti-IgE globulin serum from Behringswerke (GFR). A considerable elevation of immunoglobulin E in the patients' sera was found, at an average of 394 IU (control 124 IU). A discrepancy in serum immunoglobulin E level was established with the different clinical forms of asthma. The highest are the values with infectious-allergic astmha-424 IU. High are the values both in the treated and not-treated with corticosteroids, without an essential difference between the two patient groups. Some of the rest immunoglobulins showed also an elevationppIgG 2620 mg% and IgA 366 mg%.

  11. Immunoglobulin-E reactivity to wine glycoproteins in heavy drinkers.

    PubMed

    Gonzalez-Quintela, Arturo; Gomez-Rial, Jose; Valcarcel, Catalina; Campos, Joaquin; Sanz, Maria-Luisa; Linneberg, Allan; Gude, Francisco; Vidal, Carmen

    2011-03-01

    N-glycans from plant and invertebrate allergens can induce extensive immunoglobulin-E (IgE) cross-reactivity in vitro. IgE antibodies against these N-glycans, also termed cross-reactive carbohydrate determinants or CCDs, are prevalent in alcohol drinkers. This study investigated the prevalence and biological significance of IgE antibodies to N-glycans from wine glycoproteins in heavy drinkers. A structured questionnaire, skin prick tests, serum IgE levels, IgE-immunoblotting to wine extracts, and basophil activation tests were used to characterize 20 heavy drinkers and 10 control subjects. Eleven heavy drinkers (55%) showed IgE binding to proteins in wine extracts. The proteins were identified by mass spectrometry as grape-derived vacuolar invertase and thaumatin-like protein. Immunoblot reactivity was closely associated with the presence of IgE to CCDs and was inhibited by preincubation with a glycoconjugate containing bromelain-type N-glycans. The same conjugate, CCD-bearing allergens, and wine extracts activated basophils in patients with high-titer CCD-specific IgE but not in healthy controls. There was no relationship between immunoblot reactivity and consumption of any specific type of wine. No patient reported symptoms of hypersensitivity to Hymenoptera venom, food, or wine. In conclusion, heavy drinkers frequently show IgE reactivity to the N-glycans of wine glycoproteins. Glycans and wine glycoprotein extracts can induce basophil activation in sensitized alcoholics. The clinical significance of these findings remains to be elucidated.

  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. 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

  14. Intestinal immunoglobulins in children with coeliac disease

    PubMed Central

    Savilahti, E.

    1972-01-01

    The numbers of immunoglobulin-containing cells in jejunal biopsy specimens of 19 children with active coeliac disease aged 0·5 to 16·5 years were studied by direct immunofluorescence. Intestinal juice immunoglobulins were measured in 14 of these patients. The number of IgA-containing cells was twice and the number of IgM-containing cells 2·5 times that of age-matched controls. There were also more IgG-, IgE-, and IgD-containing cells in the jejunal mucosa of the coeliac patients, but the absolute numbers of these cells were low. The immunoglobulin content of the intestinal juice was not altered in coeliacs. A follow-up biopsy specimen was available from seven patients kept on a strict gluten-free diet for one to four months. A significant fall in the numbers of immunoglobulin-containing cells was seen, and they did not differ at that time from the controls. Two patients were followed until full normalization of the jejunal structure and they had normal numbers of immunoglobulin-containing cells. In children with coeliac disease in contrast to adult coeliacs, the study shows that the IgA-producing system is quantitatively stimulated during gluten challenge. The rapid drop in the numbers of immunoglobulin-containing cells after gluten withdrawal suggests that there is no quantitative abnormality in the local immunoglobulin-producing system of the gut in coeliac disease. ImagesFig. 3 PMID:4568803

  15. Subcutaneous immunoglobulin in treating inflammatory neuromuscular disorders

    PubMed Central

    Yoon, Min-Suk; Gold, Ralf

    2015-01-01

    Objective: Intravenous immunoglobulin administration has long been used in the treatment of autoimmune neuromuscular disorders. Immunoglobulins may be administered by intramuscular, intravenous or subcutaneous routes. Methods: This is a report on the long-term clinical follow up of six patients with inflammatory neuromuscular disorders, that is, three chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy (MMN), one inclusion body myositis (IBM) and one myasthenia gravis (MG), treated with subcutaneous immunoglobulins for a mean of 3.25 years. Results: One MMN and two CIDP patients received a weekly dose of subcutaneous immunoglobulins equivalent to intravenous immunoglobulin. One CIDP patient received a 50% dose reduction, the IBM patient received a 30% reduction and the MG patient a 20% reduction. The lower dose chosen in the majority of patients was based not only on clinical effects, but also on studies of primary immunodeficiency syndromes. One patient with CIDP showed clinical fluctuation, which was successfully treated with an adaptation of the dose of subcutaneous immunoglobulins, while the remaining patients with neuromuscular disorders had a stable clinical course for 2 years. No serious side effects were observed. Conclusions: Our results suggest that subcutaneous immunoglobulins can be an attractive alternative therapy in autoimmune neuromuscular disorders. PMID:26136842

  16. 7th International Immunoglobulin Conference: Immunodeficiencies

    PubMed Central

    Schmidt, R E; Ochs, H D

    2014-01-01

    Most primary immunodeficiency disorders (PID) are the result of single gene defects. Based on this fact, more than 240 different entities have been identified. Those PIDs with predominant antibody deficiency are treated with immunoglobulin (Ig) replacement therapy. This review focuses on the diagnosis, clinical characteristics and treatment of patients suffering from PID, or secondary immunodeficiency disorders (SID) caused, for instance, by irradiation, immunosuppressive drugs or thymectomy. Common variable immunodeficiency (CVID) is the most commonly diagnosed and least understood form of PID, with a heterogeneous range of symptoms and genotypes, requiring individualized treatment plans. This includes adjusting the dose and treatment interval, administrating Ig by intravenous or subcutaneous injection by either pump or push, and finally deciding which treatment options are best for a given patient. Ig therapy can also be used to treat immunodeficiencies resulting from lymphoproliferative and autoimmune diseases or immunosuppression following organ transplantation; however, there is an urgent need for research in this field. Accurate and early diagnosis of PID is important to ensure that optimal treatment is started early to maintain the patient's health. Detailed patient registries have been established to increase awareness of PID, as well as provide a valuable resource for further research. PMID:25546741

  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. Immunoglobulin Replacement Therapy for Primary Immunodeficiency.

    PubMed

    Sriaroon, Panida; Ballow, Mark

    2015-11-01

    Immunoglobulin replacement therapy has been standard treatment in patients with primary immunodeficiency diseases for the past 3 decades. The goal of therapy is to reduce serious bacterial infections in individuals with antibody function defects. Approximately one-third of patients receiving intravenous immunoglobulin treatment experience adverse reactions. Recent advances in manufacturing processes have resulted in products that are safer and better tolerated. Self-infusion by the subcutaneous route has become popular and resulted in better quality of life. This review summarizes the use of immunoglobulin therapy in primary immunodeficiency diseases including its properties, dosing, adverse effects, and different routes of administration.

  19. 7th International Immunoglobulin Conference: Poster presentations.

    PubMed

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    The pan-European survey provides useful information on the accessibility and trends of intravenous and subcutaneous immunoglobulin (IVIg/SCIg) therapy, which is used to treat primary immunodeficiency disorders (PIDs). Although immunoglobulin (Ig) therapy is the first-line treatment for PIDs, the mechanisms of action of Ig therapy may differ according to the condition it is used to treat. Moreover, intriguing presentations suggest that further investigation is required to understand more clearly both the haematological and immunoregulatory effects of therapeutic immunoglobulin. This can ultimately provide more information on optimizing Ig therapy efficacy, and establish whether individualized dosing regimens for patients will be conducive to better clinical outcomes. In addition to treating autoimmune and inflammatory conditions, there is evidence to suggest that immunoglobulins can potentially play a role in transplantation, which warrants further investigation for future use.

  20. Secretory immunoglobulin A and immunoglobulin G in horse saliva.

    PubMed

    Palm, Anna-Karin E; Wattle, Ove; Lundström, Torbjörn; Wattrang, Eva

    2016-11-01

    This study aimed to increase the knowledge on salivary antibodies in the horse since these constitute an important part of the immune defence of the oral cavity. For that purpose assays to detect horse immunoglobulin A (IgA) including secretory IgA (SIgA) were set up and the molecular weights of different components of the horse IgA system were estimated. Moreover, samples from 51 clinically healthy horses were tested for total SIgA and IgG amounts in saliva and relative IgG3/5 (IgG(T)) and IgG4/7 (IgGb) content were tested in serum and saliva. Results showed a mean concentration of 74μg SIgA/ml horse saliva and that there was a large inter-individual variation in salivary SIgA concentration. For total IgG the mean concentration was approx. 5 times lower than that of SIgA, i.e. 20μg IgG/ml saliva and the inter-individual variation was lower than that observed for SIgA. The saliva-serum ratio for IgG isotypes IgG3/5 and IgG4/7 was also assessed in the sampled horses and this analysis showed that the saliva-serum ratio of IgG4/7 was in general approximately 4 times higher than that of IgG3/5. The large inter-individual variation in salivary SIgA levels observed for the normal healthy horses in the present study emphasises the need for a large number of observations when studying this parameter especially in a clinical setting. Moreover, our results also indicated that some of the salivary IgG does not originate from serum but may be produced locally. Thus, these results provide novel insight, and a base for further research, into salivary antibody responses of horses.

  1. Secretion of a chimeric T-cell receptor-immunoglobulin protein.

    PubMed Central

    Gascoigne, N R; Goodnow, C C; Dudzik, K I; Oi, V T; Davis, M M

    1987-01-01

    To produce sufficient quantities of soluble T-cell receptor protein for detailed biochemical and biophysical analyses we have explored the use of immunoglobulin--T-cell receptor gene fusions. In this report we describe a chimeric gene construct containing a T-cell receptor alpha-chain variable (V) domain and the constant (C) region coding sequences of an immunoglobulin gamma 2a molecule. Cells transfected with the chimeric gene synthesize a stable protein product that expresses immunoglobulin and T-cell receptor antigenic determinants as well as protein A binding sites. We show that the determinant recognized by the anticlonotypic antibody A2B4.2 resides on the V alpha domain of the T-cell receptor. The chimeric protein associates with a normal lambda light chain to form an apparently normal tetrameric (H2L2, where H = heavy and L = light) immunoglobulin molecule that is secreted. Also of potential significance is the fact that a T-cell receptor V beta gene in the same construct is neither assembled nor secreted with the lambda light chain, and when expressed with a C kappa region it does not assemble with the chimeric V alpha C gamma 2a protein mentioned above. This indicates that not all T-cell receptor V regions are similar enough to immunoglobulin V regions for them to be completely interchangeable. Images PMID:3472243

  2. Immunoglobulin classes of Aleutian disease virus antibody.

    PubMed Central

    Porter, D D; Porter, H G; Suffin, S C; Larsen, A E

    1984-01-01

    Aleutian disease virus (ADV) persistently infects mink and causes marked hypergammaglobulinemia. Immunoglobulin class-specific antisera were used to define the total immunoglobulin of each class by radial immunodiffusion and the immunoglobulin class of ADV-specific antibody by immunofluorescence in experimentally and naturally infected mink. Electrophoretic gamma globulin closely reflects the immunoglobulin G (IgG) level in mink, and the majority of the increased immunoglobulin and ADV antibody in infected mink is IgG. IgM becomes elevated within 6 days after infection, reaches peak levels by 15 to 18 days, and returns to normal by 60 days after infection. The first ADV antibody demonstrable is IgM, and most mink have virus-specific IgM antibody for at least 85 days postinfection. Serum IgA levels in normal mink are not normally distributed, and ADV infection causes a marked elevation of IgA. Low levels of ADV-specific IgA antibody can be shown throughout the course of infection. Failure of large amounts of virus-specific IgG antibody to inhibit the reaction of virus-specific IgM and IgA antibodies suggests that the various classes of antibodies are directed against spatially different antigenic determinants. The IgM and IgA were shown not to be rheumatoid factors. PMID:6319283

  3. 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.

  4. Variability of the immunological state of germfree colostrum-deprived Minnesota miniature piglets.

    PubMed Central

    Setcavage, T M; Kim, Y B

    1976-01-01

    Minnesota miniature piglets obtained by hysterectomy and deprived of colostrum were examined for the presence of immunoglobulin by immunoelectrophoresis, double-gel diffusion, and radial immunodiffusion techniques with specific anti-immunoglobulin chain sera. A large amount of variability existed between different litters of piglets and between different piglets within the same litter, ranging from no detectable immunoglobulin in the serum to very high immunoglobulin levels approaching that of the adult pig. All known classes of porcine immunoglobulin including immunoglobulin G, immunoglobulin M, and immunoglobulin A could be found in the sera from litters where there was extensive placental damage. This contaminating immunoglobulin was shown to have antibody activity to actinophage MSP-2 even when present in very low concentrations. The low level contamination with immunoglobulin G, which was the most frequently encountered type of contaminant, was demonstrated to be similar to sow immunoglobulin G both antigenically and in its molecular size. The data demonstrates that individual piglets must be tested for immunoglobulin content rather than being assumed to be immunologically "virgin" and emphasizes the need for an intact placenta barrier to obtain piglets free from maternal immunoglobulin and devoid of antigenic stimulation. Images PMID:1262064

  5. Rearrangement of immunoglobulin light chain genes in the chicken occurs prior to colonization of the embryonic bursa of Fabricius.

    PubMed Central

    Mansikka, A; Sandberg, M; Lassila, O; Toivanen, P

    1990-01-01

    We have applied polymerase-chain-reaction-directed immunoglobulin gene analysis to study the embryonic differentiation of chicken B cells. Immunoglobulin light chain DNA segments in the rearranged configuration were amplified from cells of the intraembryonic mesenchyme as early as day 7 of incubation. We showed by sequencing that the rearranged variable region genes in these early B-cell progenitors were not different from the germ-line V lambda 1 gene (the single functional light chain variable region gene in chickens). In the bursal B lymphocytes, on the other hand, clear gene conversion events were first observed at day 15 of embryonic development. The present data indicate that rearrangement of light chain genes in the chicken occurs independently of the bursa of Fabricius and that diversification of the variable region begins only later, when the surface immunoglobulin-positive B cells are proliferating in the bursal follicles. Images PMID:2123557

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. Eastern Equine Encephalitis Treated With Intravenous Immunoglobulins.

    PubMed

    Mukerji, Shibani S; Lam, Alice D; Wilson, Michael R

    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.

  13. Immunoglobulins in tears of normal Indian people.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Mani, K.; Saha, K.

    1976-01-01

    Immunoglobulin concentrations in tears from 50 healthy Indians aged from 14 to 50 years were measured by a standard immunodiffusion method. The levels of IgA were substantial; those of IgG were very low; and IgD and IgM were not present. The mean IgA level was 24-6 mg/100 ml. PMID:1276121

  14. Nonphysiological binding of ethylene by plants.

    PubMed

    Abeles, F B

    1984-03-01

    Ethylene binding to seedling tissue of Vicia faba, Phaseolus vulgaris, Glycine max, and Triticum aestivum was demonstrated by determining transit time required for ethylene to move through a glass tube filled with seedling tissue. Transit time for ethylene was greater than that for methane indicating that these tissues had an affinity for ethylene. However, the following observations suggest that the binding was not physiological. Inhibitors of ethylene action such as Ag(+) ions and CO(2) did not decrease binding. Mushrooms which have no known sites of ethylene action also demonstrated ethylene binding. The binding of acetylene, propylene, ethylene, propane, and ethane more closely followed their solubility in water than any known physiological activity.

  15. Membrane-associated immunoglobulins of human lymphocytes in immunologic disorders

    PubMed Central

    Nicod, Isabelle; Girard, J. P.; Cruchaud, A.

    1973-01-01

    Membrane-associated immunoglobulins of peripheral blood lymphocytes were studied by indirect immunofluorescence for γ, α, μ, κ and λ chains in healthy subjects and patients with immunologic disease. In healthy subjects, heavy chains were found on 30·7% of lymphocytes (γ 15·3%, α 7·2% and μ 8·2%) and light chains on 32·8% of cells (κ 20·4% and λ 12·4%). Patients with humoral immune deficiencies had fewer immunoglobulin-bearing cells; sarcoidosis or thymectomy patients had normal or decreased immunoglobulin-bearing lymphocytes; cells with light chains were fewer than those with heavy chains on their lymphocytes. In some cases, normal levels of serum immunoglobulins were found in the absence of the corresponding immunoglobulin-bearing cells, and in others normal immunoglobulin-bearing lymphocytes were present in the absence of the corresponding serum immunoglobulins. These data suggest that (1) immunoglobulin-bearing lymphocytes in blood do not reflect the condition of immunoglobulin-synthesizing cells in peripheral lymphoid tissues, and (2) in certain immunologic disorders, either some B-lymphocytes do not synthesize immunoglobulins, or immunoglobulins are in such a situation that the whole molecule or part of the molecule is not visualized by current methods. PMID:4587505

  16. Phylogeny, genomic organization and expression of lambda and kappa immunoglobulin light chain genes in a reptile, Anolis carolinensis.

    PubMed

    Wu, Qian; Wei, Zhiguo; Yang, Zhi; Wang, Tao; Ren, Liming; Hu, Xiaoxiang; Meng, Qingyong; Guo, Ying; Zhu, Qinghong; Robert, Jacques; Hammarström, Lennart; Li, Ning; Zhao, Yaofeng

    2010-05-01

    The reptiles are the last major taxon of jawed vertebrates in which immunoglobulin light chain isotypes have not been well characterized. Using the recently released genome sequencing data, we show in this study that the reptile Anolis carolinensis expresses both lambda and kappa light chain genes. The genomic organization of both gene loci is structurally similar to their respective counterparts in mammals. The identified lambda locus contains three constant region genes each preceded by a joining gene segment, and a total of 37 variable gene segments. In contrast, the kappa locus contains only a single constant region gene, and two joining gene segments with a single family of 14 variable gene segments located upstream. Analysis of junctions of the recombined VJ transcripts reveals a paucity of N and P nucleotides in both expressed lambda and kappa sequences. These results help us to understand the generation of the immunoglobulin repertoire in reptiles and immunoglobulin evolution in vertebrates.

  17. Immunoglobulin expression and synthesis by human haemic cell lines.

    PubMed Central

    Gordon, J; Hough, D; Karpas, A; Smith, J L

    1977-01-01

    Twenty-six human cell lines derived from a variety of lymphoid and non-lymphoid malignancies, were investigated for their immunological markers, with special reference to the class of immunoglobulin expressed. Twenty-five of the lines stained positively for surface immunoglobulin and IgD together with IgM proved to be the major immunoglobulin classes on these cells. Six of the lines were chosen for a study of their immunoglobulin synthesis patterns over an 18-h period and the immunoglobulin produced was analysed on SDS-polyacrylamide gel electrophoresis. Patterns obtained from the cell lines were similar to that from normal lymph node lymphocytes and differed markedly to plasma cells. Two of the cell lines had abnormal immunoglobulin synthesis patterns characterized as free light chains in one case. The cell lines are evaluated for their usefulness as models of immunoglobulin synthesis and analogues of normal and neoplastic states. PMID:608682

  18. A Novel Immunoglobulin-Immunoglobulin Interaction in Autoimmunity

    PubMed Central

    Kawa, Shigeyuki; Kitahara, Kei; Hamano, Hideaki; Ozaki, Yayoi; Arakura, Norikazu; Yoshizawa, Kaname; Umemura, Takeji; Ota, Masao; Mizoguchi, Sadaaki; Shimozuru, Yasunori; Bahram, Seiamak

    2008-01-01

    Well over six decades since its first description, the Rheumatoid Factor (RF)—autoantibodies recognizing Fc (constant) portion of IgG through their own Fab (antigen binding variable segments)—is believed to have come of age. Autoimmune pancreatitis is a unique form of pancreatitis, biologically characterized by an elevated serum IgG4 concentration. Given the fact that IgG4 myeloma proteins can act as RF, we initially hypothesized that IgG4 in autoimmune pancreatitis might do likewise, hence potentially contributing to disease pathogenesis. Indeed Western blotting clearly showed that IgG4 binds to IgG1 κ, IgG2 κ, IgG3 κ myeloma proteins, as well as to IgG Fc, in line with a typical RF activity. Further experiments however unraveled the unexpected fact that unlike hitherto known RF, IgG4 does not engage IgG Fc through its Fab, but its very own Fc. These data therefore collectively describe a Novel RF (NRF) in autoimmune pancreatitis. In the future, the relevance of NRF, beyond autoimmune pancreatitis, in both diagnosis/prognosis as well as pathophysiology of autoimmune and other systemic diseases where IgG4's role seems paramount, needs to be systematically assessed. PMID:18297131

  19. Subcutaneous immunoglobulin therapy for inflammatory neuropathy: current evidence base and future prospects.

    PubMed

    Rajabally, Yusuf A

    2014-06-01

    Intravenous immunoglobulin therapy is of proven effect in chronic inflammatory neuropathies, including chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). In more recent years, there have been a number of anecdotal case reports and small series, followed by a few trials of variable design, of subcutaneous immunoglobulin therapy in these neuropathies. To date, limited evidence suggests that the subcutaneous route may be a more clinically effective, better-tolerated, at least cost-equivalent and a more patient-friendly option than the still more used intravenous alternative. Long-term efficacy is not as yet established in neuropathic indications by randomised controlled clinical trial evidence, and it is likely that the subcutaneous route may not be suitable in all cases with some hints to this effect appearing from the limited data available to date. Further studies are ongoing, including those of dose comparison, and more are likely to be planned in future. The literature on the use of subcutaneous immunoglobulin therapy in chronic inflammatory neuropathy is reviewed here. The current use in clinical practice, day-to-day benefits, including quality of life measures and health economics as published thus far, are evaluated. The limitations of this form of treatment in CIDP and MMN are also analysed in the light of current literature and taking into account the remaining unknowns. Future prospects and research with this mode of immunoglobulin therapy administration are discussed.

  20. On the genomics of immunoglobulins in the gray, short-tailed opossum Monodelphis domestica.

    PubMed

    Wang, Xinxin; Olp, Jonathan J; Miller, Robert D

    2009-08-01

    Annotated maps of the IGH, IGK, and IGL loci in the gray, short-tailed opossum Monodelphis domestica were generated from analyses of the available whole genome sequence for this species. Analyses of their content and organization confirmed a number of previous conclusions based on characterization of complementary DNAs encoding opossum immunoglobulin heavy and light chains and limited genomic analysis, including (a) the predominance of a single immunoglobulin heavy chain variable region (IGHV) subgroup and clan, (b) the presence of a single immunoglobulin (Ig)G subclass, (c) the apparent absence of an IgD, and (d) the general organization and V gene complexity of the IGK and IGL light chain loci. In addition, several unexpected discoveries were made including the presence of a partial V to D, germline-joined IGHV segment, the first germline-joined Ig V gene to be found in a mammal. In addition was the presence of a larger number of IGKV subgroups than had been previously identified. With this report, annotated maps of the major histocompatibility complex, T-cell receptor, and immunoglobulin loci have been completed for M. domestica, the only non-eutherian mammalian species for which this has been accomplished, strengthening the utility of this species as a model organism.

  1. 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.

  2. Cell-type preference of immunoglobulin kappa and lambda gene promoters.

    PubMed Central

    Picard, D; Schaffner, W

    1985-01-01

    Immunoglobulin gene constant regions are known to be associated with strictly tissue-specific enhancer elements. Until recently the promoter of the variable region, which becomes linked to the constant region by somatic rearrangement, could have been viewed as a passive recipient of the enhancer stimulus. Here we show that the promoters of the immunoglobulin kappa and lambda light chain genes are approximately 20-30 times more active in lymphoid cells than in non-lymphoid cells. To avoid the problem of differential mRNA stability upon transfection of immunoglobulin genes into non-lymphoid cells we have constructed chimeric genes. All kappa mRNA sequences were progressively deleted to fuse the kappa gene promoter to a globin gene coding body. A similar chimeric gene was constructed with the promoter of the lambda gene. The cell-type preference of the promoter may be exploited during B-lymphocyte differentiation to regulate the immunoglobulin gene promoter independently from the enhancer. Images Fig. 2. Fig. 4. Fig. 5. Fig. 6. PMID:2998757

  3. Increased (18)F-fluorodeoxyglucose uptake in benign, nonphysiologic lesions found on whole-body positron emission tomography/computed tomography (PET/CT): accumulated data from four years of experience with PET/CT.

    PubMed

    Metser, Ur; Even-Sapir, Einat

    2007-05-01

    The use of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the field of oncology is rapidly evolving; however, (18)F-FDG is not tumor specific. Aside from physiological uptake (18)F-FDG also may accumulate in benign processes. Knowledge of these (18)F-FDG-avid nonmalignant lesions is essential for accurate PET interpretation in oncologic patients to avoid a false-positive interpretation. Through the systematic review of the reports of PET/computed tomography (CT) studies performed in oncologic patients during a 6-month period, we found benign nonphysiological uptake of (18)F-FDG in more than 25% of studies. In half of these, (18)F-FDG uptake was moderate or marked in intensity, similar to that of malignant sites. A total of 73% of benign lesions were inflammatory in nature, with post-traumatic bone and soft-tissue abnormalities (including iatrogenic injury) and benign tumors accounting for the remainder. The differentiation of benign from malignant uptake of (18)F-FDG on PET alone may be particularly challenging as a result of the low anatomical resolution of PET and paucity of anatomical landmarks. Fusion imaging, namely PET/CT, has been shown to improve not only the sensitivity of PET interpretation but also its specificity. Aside from better anatomical localization of lesions on PET/CT, morphological characterization of lesions on CT often may improve the diagnostic accuracy of nonspecific (18)F-FDG uptake. Correlation with CT on fused PET/CT data may obviate the need for further evaluation or biopsy in more than one-third of scintigraphic equivocal lesions. Familiarity with (18)F-FDG-avid nonmalignant lesions also may extend the use of (18)F-FDG-PET imaging beyond the field of oncology. We have tabulated our experience with benign entities associated with increased (18)F-FDG uptake on whole-body PET/CT from 12,000 whole-body (18)F-FDG-PET/CT studies performed during a 4-year period.

  4. Lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

    PubMed

    Khong, Peter; Enno, Alar; Darwish, Balsam

    2014-02-01

    We present the unusual case of a 33-year-old woman who presented with a 2 year history of amenorrhoea and an expanding sellar lesion. Initial MRI revealed a lesion in the pituitary fossa, thought to be a pituitary adenoma. One year later, the lesion had enlarged by 5mm, with associated enhancement of the dura of the planum sphenoidale and pituitary stalk. Histopathology revealed a lymphocytic and plasma cell inflammatory infiltrate suggestive of lymphoplasmacytic hypophysitis associated with immunoglobulin G4.

  5. Immunoglobulin therapy in idiopathic hypothalamic dysfunction.

    PubMed

    Huppke, Peter; Heise, Alexander; Rostasy, Kevin; Huppke, Brenda; Gärtner, Jutta

    2009-09-01

    Idiopathic hypothalamic dysfunction is a rare disorder presenting at age 3-7 years. Severe hypothalamic and brainstem dysfunction leads to death in 25% of patients. The disease is presumed to be autoimmune, or in some cases paraneoplastic. No successful treatment has been reported. Patient V. developed hyperphagia, hypersomnia, and extreme aggression at age 7 years, accompanied by episodes of hyperthermia, hypothermia, sinus bradycardia, hypernatremia, hyponatremia, persistent hyperprolactinemia, hypothyroidism, and growth-hormone deficiency. At age 9 years, a diagnosis of idiopathic hypothalamic dysfunction was rendered, and immunoglobulin therapy was commenced. Nine courses of immunoglobulins, at a dose of 2 g/kg every 4 weeks, were administered. Reproducible improvements in behavior and no further episodes of hyponatremia or hypernatremia and sinus bradycardia were evident. The endocrinologic abnormalities and poor thermoregulation remained. Administration of immunoglobulins during late stages of idiopathic hypothalamic dysfunction led to improvement in some but not all signs. Assuming an autoimmune basis for this disorder, treatment during early stages of disease should be more effective. To facilitate such early treatment, increased awareness of this disorder is necessary, to allow for early diagnosis.

  6. Antarctic teleost immunoglobulins: more extreme, more interesting.

    PubMed

    Coscia, Maria Rosaria; Varriale, Sonia; Giacomelli, Stefano; Oreste, Umberto

    2011-11-01

    We have investigated the immunoglobulin molecule and the genes encoding it in teleosts living in the Antarctic seas at the constant temperature of -1.86 °C. The majority of Antarctic teleosts belong to the suborder Notothenioidei (Perciformes), which includes only a few non-Antarctic species. Twenty-one Antarctic and two non-Antarctic Notothenioid species were included in our studies. We sequenced immunoglobulin light chains in two species and μ heavy chains, partially or totally, in twenty species. In the case of heavy chain, genomic DNA and the cDNA encoding the secreted and the membrane form were analyzed. From one species, Trematomus bernacchii, a spleen cDNA library was constructed to evaluate the diversity of VH gene segments. T. bernacchii IgM, purified from the serum and bile, was characterized. Homology Modelling and Molecular Dynamics were used to determine the molecular structure of T. bernacchii and Chionodraco hamatus immunoglobulin domains. This paper sums up the previous results and broadens them with the addition of unpublished data.

  7. [Serum and secretory immunoglobulins in allergic diseases].

    PubMed

    Atovmian, O I; German, G P; Chernokhvostova, E V

    1985-07-01

    A total of 158 patients with pollinosis, bronchial asthma, urticaria and Quincke's edema were examined. The immunoglobulin and C3 levels in sera and the immunoglobulin and albumin levels in saliva were determined by the method of single radial immunodiffusion with the corresponding monospecific antisera. In all the groups of patients subjected to examination the presence of polyclonal hypergammaglobulinemia was detected, which was manifested by a rise in the levels of IgG, IgA and especially IgM; the level of IgD was low. A decrease in the level of C3 was detected in pollinosis patients in the absence of the exacerbation of the disease. No circulating immune complexes were detected. An essential increase in the level of IgG in saliva was revealed, which was due to the local synthesis of this immunoglobulin. In winter the level of salivary IgA in pollinosis patients was found to be essentially below normal, but at the period of exacerbation it increased twofold, probably in response to local stimulation with antigen-allergen. Patients with bronchial asthma and pollinosis were found to have a high level of free secretory component (SC); in pollinosis the level of free SC sharply increased during the stage of exacerbation, which was due to the increase of its synthesis and secretion by the epithelial cells of the mucous membranes. The importance of these data for the pathogenesis of allergic diseases are discussed.

  8. [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.

  9. [Immunoglobulins in patients with Nocardia brasiliensis actinomycetoma].

    PubMed

    Méndez-Tovar, L J; Mondragón-González, R; Manzano-Gayosso, P; López-Martínez, R; Hernández-Hernández, F; Bonifaz, A; Anides Fonseca, A; Araiza, J; Vega-López, F

    2004-01-01

    Considering that some authors have reported an increasing of some immunoglobulins in actinomycetoma patients, in this study we propose to determine differential production of IgG1, IgG2, IgG3, IgG4 and IgGM in 25 patients with actinomycetoma and 25 healthy individuals from a mycetoma endemic area. Immunoglobulins were determined by ELISA technique. To sensibilize the plates, six Nocardia brasiliensis antigens were used: a crude antigen denominated NB and five derivatives (NB2, NB4, NB6, NB8 and NB10) obtained by their isoelectric point. Results showed that all IgG subclasses were higher in the patients' sera than in control sera, with a maximal difference to IgG3 and IgG4. To the latter subclass, six antigens were highly reactives. IgM levels were similar in both groups. As it occurs in other infections, in the actinomycetoma pathogenesis probably participate the increase or deficiency of a determined immunoglobulin class, as well as the relationship between different subclasses.

  10. Symptomatic Primary Selective Immunoglobulin M Deficiency with Nonprotective Pneumococcal Titers Responsive to Subcutaneous Immunoglobulin Treatment.

    PubMed

    Patel, Shiven S; Fergeson, Jennifer E; Glaum, Mark C; Lockey, Richard F

    2016-01-01

    Selective immunoglobulin M deficiency (SIgMD) is a rare disorder with varying clinical features. The prevalence of SIgMD is 0.03-3%. Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.

  11. Successful treatment of systemic lupus erythematosus with subcutaneous immunoglobulin.

    PubMed

    Brasileiro, A; Fonseca Oliveira, J; Pinheiro, S; Paiva-Lopes, M J

    2016-05-01

    The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients.

  12. Immunoglobulin patterns in humans over 95 years of age.

    PubMed Central

    Radl, J; Sepers, J M; Skvaril, F; Morell, A; Hijmans, W

    1975-01-01

    Immunoglobulin patterns were investigated in seventy-three volunteers older than 95 years. An idiopathic paraproteinaemia was found in 19% of the cases. A restriction of heterogeneity and an imbalance in the kappa/lambda ratio of the immunoglobulins was seen in a number of other sera. Determinations of immunoglobulin levels in sera of individuals without paraproteinaemia showed an increase in IgA and IgG. The quantitations of the IgG subclasses demonstrated that an increase in the IgG1 and IgG3 subclasses is responsible for the elevated level of the IgG. The variation in the immunoglobulin levels increased significantly with age of IgM and for the three major IgG subclasses. No abnormalities were found in the urine or in the mixed saliva. These results indicate that selective changes in the extent of the antibody-immunoglobulin repertoire characterize the immunoglobulin pattern of ageing man. PMID:1212818

  13. Synthesis of immunoglobulins by human endocervix in organ culture.

    PubMed Central

    Cowan, M. E.; Buchan, A.; Skinner, G. R.

    1982-01-01

    The synthesis of immunoglobulins by the uterine cervix was investigated in an endocervical organ-culture system. Using Ouchterlony immunodiffusion gels immunoglobulin G, immunoglobulin A and secretory piece were detected in washings of endocervical explants and in explant incubation medium. Synthesis of immunoglobulin in the organ-culture system was investigated by polyacrylamide-gel electrophoresis of radiolabelled polypeptides; 2 polypeptides co-migrated with the heavy and light chains of a reference polyclonal immunoglobulin G and were confirmed, by use of anti-human globulin and iodinated staphylococcal protein A, to be the heavy and light chains of immunoglobulin G. This experimental system will provide a useful model in future investigations of the efficacy of a local vaccine in human subjects. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:6803822

  14. Synthesis of immunoglobulins by human endocervix in organ culture.

    PubMed

    Cowan, M E; Buchan, A; Skinner, G R

    1982-04-01

    The synthesis of immunoglobulins by the uterine cervix was investigated in an endocervical organ-culture system. Using Ouchterlony immunodiffusion gels immunoglobulin G, immunoglobulin A and secretory piece were detected in washings of endocervical explants and in explant incubation medium. Synthesis of immunoglobulin in the organ-culture system was investigated by polyacrylamide-gel electrophoresis of radiolabelled polypeptides; 2 polypeptides co-migrated with the heavy and light chains of a reference polyclonal immunoglobulin G and were confirmed, by use of anti-human globulin and iodinated staphylococcal protein A, to be the heavy and light chains of immunoglobulin G. This experimental system will provide a useful model in future investigations of the efficacy of a local vaccine in human subjects.

  15. [Development and study of properties of immunoglobulins against Lassa fever].

    PubMed

    Krasnianskiĭ, V P; Gradoboev, V N; Borisevich, I V; Potryvaeva, N V; Lebedinskaia, E V; Chernikova, N K; Timan'kova, G D

    1997-01-01

    A horse may serve the producer of immune antiserum to Lassa virus. Specific immunoglobulin with at least 1:512 titer of virus-neutralizing antibodies to Lassa fever was obtained by alcohol sedimentation after Cohn from the blood serum of immunized horses. The preparation does not differ from heterologous commercial immunoglobulins. Preclinical studies of immunoglobulin to Lassa fever demonstrated its safety and a high specific activity. The agent can be injected both alone and in combination with virasole.

  16. 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.

  17. 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.

  18. Single radial immunodiffusion analysis for quantitation of colostral immunoglobulin concentration.

    PubMed

    Fleenor, W A; Stott, G H

    1981-05-01

    Relative accuracy of the single radial immunodiffusion technique to measure immunoglobulin concentrations of colostral preparations (whey, whole, or fat-free) has been assessed. Fresh colostrum samples were analyzed for major constituents. Gammaglobulin as a standard was compared to total immunoglobulin concentration derived from single radial immunodiffusion analysis of colostral preparations with no differences except between standard and whey. Differences were in part from either enhancement or interference of immunoglobulin diffusion by colostral constituents. Removal of casein and fat during whey preparations caused a concentrating effect upon immunoglobulin constituents resulting in exaggerated precipitin rings. Whey has produced unreliable results: therefore, whole colostrum is recommended for single radial immunodiffusion analysis.

  19. Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP batch 1.

    PubMed

    Sandberg, E; Daas, A; Behr-Gross, M-E

    2006-11-01

    A study was carried out by the European Directorate for the Quality of Medicines (EDQM) as part of the joint Biological Standardisation Programme of the Council of Europe and the European Commission with the aim to establish replacement batches of the European Pharmacopoeia (Ph. Eur.) human immunoglobulin Biological Reference Preparation (BRP) batch 2. Twenty-eight laboratories participated in this study. The suitability of the candidate reference preparations to serve as working references in the tests for distribution of the molecular size, anticomplementary activity and Fc function, in accordance with the specifications of the Ph. Eur. monographs Human normal immunoglobulin for intravenous administration (0918), Human normal immunoglobulin (0338) and Anti-T lymphocyte immunoglobulin for human use, animal (1928) was demonstrated. The candidates were therefore established as human immunoglobulin BRP batch 3 and Human immunoglobulin (molecular size) BRP batch 1. The prescribed use of the latter BRP is limited to the test for distribution of molecular size.

  20. 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.

  1. [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.

  2. [Secretory immunoglobulin A in amniotic fluid].

    PubMed

    Briese, V; Straube, W; Brock, J; Lorenz, U

    1983-01-01

    Secretory immunoglobulin A (S-IgA) was estimated in amniotic fluid samples by means of the single radial immunodiffusion according to Mancini. A monospecific antiserum against human secretory component was used. 163 amniotic fluid samples from normal pregnancies and risk pregnancies respectively were investigated. Within the 3rd trimenon the S-IgA content in amniotic fluid increased significantly. With respect to literature and examinations performed previously a connection between S-IgA content in amniotic fluid and fetal lung maturity seems to be possible.

  3. 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...

  4. Passive transfer of colostral immunoglobulins in calves.

    PubMed

    Weaver, D M; Tyler, J W; VanMetre, D C; Hostetler, D E; Barrington, G M

    2000-01-01

    Passive transfer of colostral immunoglobulins has long been accepted as imperative to optimal calf health. Many factors, including timing of colostrum ingestion, the method and volume of colostrum administration, the immunoglobulin concentration of the colostrum ingested, and the age of the dam have been implicated in affecting the optimization of absorption. The practice of colostrum pooling, the breed and presence of the dam, and the presence of respiratory acidosis in the calf also may affect passive transfer. Various tests have been reported to accurately measure passive transfer status in neonatal calves. The radial immunodiffusion and the enzyme-linked immunosorbent assay (ELISA) are the only tests that directly measure serum IgG concentration. All other available tests including serum total solids by refractometry, sodium sulfite turbidity test, zinc sulfate turbidity test, serum gamma-glutamyl transferase activity, and whole blood glutaraldehyde gelation estimate serum IgG concentration based on concentration of total globulins or other proteins whose passive transfer is statistically associated with that of IgG. This paper presents a comprehensive review of the literature of passive transfer in calves including factors that affect passive transfer status, testing modalities, effects of failure of passive transfer on baseline mortality, consequences of failure of passive transfer, and some treatment options. Many previously accepted truisms regarding passive transfer in calves should be rejected based on the results of recent research.

  5. 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.

  6. 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

  7. 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

  8. Genomic structure and expression of immunoglobulins in Squamata.

    PubMed

    Olivieri, David N; Garet, Elina; Estevez, Olivia; Sánchez-Espinel, Christian; Gambón-Deza, Francisco

    2016-04-01

    The Squamata order represents a major evolutionary reptile lineage, yet the structure and expression of immunoglobulins in this order has been scarcely studied in detail. From the genome sequences of four Squamata species (Gekko japonicus, Ophisaurus gracilis, Pogona vitticeps and Ophiophagus hannah) and RNA-seq datasets from 18 other Squamata species, we identified the immunoglobulins present in these animals as well as the tissues in which they are found. All Squamata have at least three immunoglobulin classes; namely, the immunoglobulins M, D, and Y. Unlike mammals, however, we provide evidence that some Squamata lineages possess more than one Cμ gene which is located downstream from the Cδ gene. The existence of two evolutionary lineages of immunoglobulin Y is shown. Additionally, it is demonstrated that while all Squamata species possess the λ light chain, only Iguanidae species possess the κ light chain.

  9. Rapid method to detect rubella immunoglobulin M and immunoglobulin A antibodies.

    PubMed Central

    Schmitz, H; Shimizu, H; Kampa, D; Doerr, H W

    1975-01-01

    Immunoglobulin (Ig) G was removed from serum specimens by precipitation with gamma chain-specific anti-human IgG of rabbit origin. The remaining rubella virus-specific IgM (and IgA) antibodies were then detected by the rubella hemagglutination-inhibition test. This procedure has proven to be as reliable as estimations carried out with IgM fractions separated on a sucrose density gradient. PMID:1176596

  10. Serum immunoglobulin profile in normal Kashmiri adults.

    PubMed

    Bhat, G A; Mubarik, M; Bhat, M Y

    1995-01-01

    Serum levels of the immunoglobulins IgG, IgA and IgM were estimated in 102 apparently healthy Kashmiri adults in the age group of 16-60 years, using single radial immunodiffusion method of Mancini et al. The mean serum levels of IgG, IgA and IgM were observed to be 1289.19 +/- 234.9, 216.18 +/- 50.70 and 118.97 +/- 41.88 respectively. No significant difference in the mean serum levels was observed between the two sexes as such, but IgM showed a significant increase in females in the age group of 16-30 years. IgA showed a significant increase with age, with no such increase in case of IgG and IgM.

  11. Immunoglobulins in tear in trachoma patients.

    PubMed Central

    Sen, D. K.; Sarin, G. S.; Saha, K.

    1977-01-01

    Tear immunoglobulin concentrations have been measured in 100 healthy people and 62 patients in different stages of trachoma. In healthy people the average IgA level was 27-8 mg/100 ml. There was no significant difference in the IgA level in various age groups and between the sexes. IgG was detected in 92 samples, and it was less than 1 mg/100 ml. IgM in tears was detected in only one sample. IgD was not detected in any specimen. In tracoma cases, the mean IgA level was found to be significantly lower (22-0 mg/100 ml) than in healthy people. There was no significant difference in IgA level between different stages of trachoma, IgG, IgD, and IgM could not be detected in any sample from the trachoma cases. PMID:856248

  12. 7th International Immunoglobulin Conference: Immunomodulation

    PubMed Central

    Danieli, M G; Shoenfeld, Y

    2014-01-01

    Rheumatoid arthritis (RA) is a debilitating autoimmune disease that is usually treated aggressively to slow the rate of joint destruction. The therapeutic strategy used at the French centre, described here, is to use the non-biological disease-modifying drug, methotrexate, as first-line therapy and to add biological agents as second-line treatment. The two other autoimmune diseases discussed in this session were immunobullous skin diseases, and secondary recurrent miscarriage (RM). In the former conditions, low levels of pathogenic autoantibodies can be achieved with adjuvant intravenous immunoglobulin (IVIg) therapy, usually in combination with an immunosuppressant. Secondary RM has an autoimmune basis, as shown by high tumour necrosis factor (TNF)-α levels and specific human leucocyte antigen (HLA) polymorphisms. Although the mechanism is not yet known, IVIg may also be an effective treatment, despite the generally low doses used in published studies. PMID:25546788

  13. 7(th) International Immunoglobulin Conference: Poster presentations.

    PubMed

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-12-01

    Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the

  14. 7th International Immunoglobulin Conference: Poster Presentations

    PubMed Central

    Warnatz, K; Ballow, M; Stangel, M; Bril, V

    2014-01-01

    Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the

  15. SUPPRESSION OF IMMUNOGLOBULIN CLASS SYNTHESIS IN MICE

    PubMed Central

    Lawton, Alexander R.; Asofsky, Richard; Hylton, Martha B.; Cooper, Max D.

    1972-01-01

    Germfree BALB/c mice have been treated from birth with intraperitoneal injections of purified goat antibodies to mouse IgM. The treated mice, and controls which had received an equivalent amount of goat γ-globulin, were sacrificed at 8 or 13 wk of age. Compared to controls, mice given anti-µ (a) had very few germinal centers in spleen and lymph node, (b) had decreased numbers of mature plasma cells synthesizing IgM and IgG1 in spleen, and virtual absence of IgA-synthesizing plasma cells in the gut, (c) had greatly diminished numbers of B lymphocytes bearing membrane-bound immunoglobulins of the IgM, IgG1, IgG2, and IgA classes in spleen, (d) had reduced synthesis of IgM, IgG2, and IgA by in vitro spleen cultures, and (e) had significant decreases in serum levels of IgM, IgG1, IgG2, and IgA. The treated animals failed to make antibodies to ferritin after hyperimmunization, and lacked natural antibodies to sheep erythrocytes. These results indicate that cells ultimately committed to synthesis of IgG1, IgG2, and IgA immunoglobulins are derived from cells which have expressed IgM determinants at an earlier stage of differentiation. They are consistent with a proposed two-stage model for plasma cell differentiation. The first stage is antigen independent, involves sequential activation of Cµ, Cγ, and Cα genes by progeny of a single stem cell, and results in the formation of B lymphocytes bearing membrane-bound recognition antibodies of each class. The second, antigen-dependent, stage results in formation of mature plasmacytes and memory cells. PMID:4551216

  16. Immunoglobulin genetics of Ornithorhynchus anatinus (platypus) and Tachyglossus aculeatus (short-beaked echidna).

    PubMed

    Belov, Katherine; Hellman, Lars

    2003-12-01

    In this paper, we review data on the monotreme immune system focusing on the characterisation of lymphoid tissue and of antibody responses, as well the recent cloning of immunoglobulin genes. It is now known that monotremes utilise immunoglobulin isotypes that are structurally identical to those found in marsupials and eutherians, but which differ to those found in birds and reptiles. Monotremes utilise IgM, IgG, IgA and IgE. They do not use IgY. Their IgG and IgA constant regions contain three domains plus a hinge region. Preliminary analysis of monotreme heavy chain variable region diversity suggests that the platypus primarily uses a single VH clan, while the short-beaked echidna utilises at least 4 distinct VH families which segregate into all three mammalian VH clans. Phylogenetic analysis of the immunoglobulin heavy chain constant region gene sequences provides strong support for the Theria hypothesis. The constant region of IgM has proven to be a useful marker for estimating the time of divergence of mammalian lineages.

  17. Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

    NASA Astrophysics Data System (ADS)

    Corcoran, Martin M.; Phad, Ganesh E.; Bernat, Néstor Vázquez; Stahl-Hennig, Christiane; Sumida, Noriyuki; Persson, Mats A. A.; Martin, Marcel; Hedestam, Gunilla B. Karlsson

    2016-12-01

    Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool.

  18. Efficacy of subcutaneous immunoglobulins in primary immunodeficiency with Crohn's-like phenotype: report of a case.

    PubMed

    Sanges, M; Spadaro, G; Miniero, M; Mattera, D; Sollazzo, R; D'Armiento, F P; De Palma, G D; Pecoraro, A; Borrelli, F; Genovese, A; D'Arienzo, A

    2015-01-01

    Common variable immune deficiency (CVID) is the most frequent primary immunodeficiency in adults. In CVID, the prevalence of gastrointestinal manifestations ranges between 2 and 50% with a complication-related morbidity second only to that of the respiratory tract. In some cases, clinical and endoscopic features are undistinguishable from those of inflammatory bowel disease (IBD). We describe the case of a 28-year-old man in which a diagnosis of Crohn's disease was firstly suspected. Subsequently, a diagnosis of Crohn's-like disease in a patient with CVID was made and a replacement therapy with human normal immunoglobulin intravenously was started. Unfortunately, serum IgG levels remained below 2.0 g/l in pre-infusional controls with persistence of gastrointestinal symptoms and malnutrition despite anti-inflammatory therapy (mesalazine, corticosteroids). Then, the patient began treatment with human normal immunoglobulins administered subcutaneously. The follow-up visits showed a progressive increase in serum IgG. Moreover, the patient reported improvement of gastrointestinal symptoms with reduction of diarrhoea, and laboratory tests showed a progressive and significant improvement. We confirm that therapy with subcutaneously administered immunoglobulins is safe and effective. In addition, our observations indicate that, for patients with CVID and enteropathic complications, replacement therapy with subcutaneous IgG may be the treatment of choice.

  19. Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity

    PubMed Central

    Corcoran, Martin M.; Phad, Ganesh E.; Bernat, Néstor Vázquez; Stahl-Hennig, Christiane; Sumida, Noriyuki; Persson, Mats A.A.; Martin, Marcel; Hedestam, Gunilla B. Karlsson

    2016-01-01

    Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool. PMID:27995928

  20. 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.

  1. Surface immunoglobulin of guinea-pig leukaemic lymphocytes.

    PubMed Central

    Stevenson, G T; Eady, R P; Hough, D W; Jurd, R D; Stevenson, F K

    1975-01-01

    The surface immunoglobulin of the transplantable L2C leukaemia of strain 2 guinea-pigs has been investigated. The immunoglobulin is seen to be synthesized when the cells are maintained in culture, indicating its intrinsic origin. Immunolabelling of the cell surface and immunochemical study of the Fab released by limited surface proteolysis indicate the presence of immunoglobulin of class IgM. IgG and free light chains were not detected, and there is unlikely to be an appreciable amount of immunoglobulin of any other class. The amount of immunoglobulin present, in terms of 4-chain monomers, is approximately 100,000 molecules per cell. Its half-life, calculated from the rate of reappearance in vitro of surface Fab after proteolytic clearing, is approximately 5 hours. Immunoglobulin secreted into the environment appears to arise predominantly or entirely from the cell surface: there is no evidence of an appreciable export of immunoglobulin which does not have a surface phase. Papain at 0.06 mg/ml rapidly removes the surface Fab. Residual Fcmu can then be detected by immunofluorescence, suggesting that papain cleaves surface IgM at a hinge region with the molecule in situ on the membrane. The released Fab is only moderately susceptible to degradation by papain at the enzyme: substrate ratio prevailing. It has been possible to isolate it from the papain digest by immuno-adsorption, with a notional yield of 75 mug per 10-10 cells, and then to prepare antisera against it. PMID:48498

  2. 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

  3. [Replacement therapy with subcutaneous immunoglobulin in primary immunodeficiency in children].

    PubMed

    Pac, Małgorzata

    2011-06-01

    Primary antibody deficiency (PAD) is the most common form of primary immunodeficiency (PID), and presents up to 60-70% of PID. The hallmark of PAD are low antibody level and recurrent infections. Patients require life-long immunoglobulin replacement therapy. Now they can be treated either with intravenous (IVIG) or subcutaneous (SCIG) immunoglobulin. The last one is indicated in patients with unacceptable adverse reactions to the intravenous immunoglobulin preparations, with poor vein access or willing to improve the quality of their life. Several data and clinical trials proved that SCIG therapy is at least as safe and efficacious as IVIG to prevent infections in patients with PAD.

  4. A year in the life of the immunoglobulin superfamily.

    PubMed

    Williams, A F

    1987-01-01

    The superfamily of molecules with immunoglobulin-like domains has recently been gaining new members-largely on the basis of sequence homology. Here Alan Williams reviews this new work and reveals how the comparison of sequence patterns enables decisions on membership to be made. Accommodation of the new structures demands the provision of new categories, and forces the abandonment of the conserved disulphide bond as the last invariant characteristic of an immunoglobulin-type domain. They may, however, provide more dues to the origins and evolution of the immunoglobulin superfamily.

  5. 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.

  6. 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.

  7. Cerebrospinal-fluid-derived immunoglobulin G of different multiple sclerosis patients shares mutated sequences in complementarity determining regions.

    PubMed

    Singh, Vaibhav; Stoop, Marcel P; Stingl, Christoph; Luitwieler, Ronald L; Dekker, Lennard J; van Duijn, Martijn M; Kreft, Karim L; Luider, Theo M; Hintzen, Rogier Q

    2013-12-01

    B lymphocytes play a pivotal role in multiple sclerosis pathology, possibly via both antibody-dependent and -independent pathways. Intrathecal immunoglobulin G in multiple sclerosis is produced by clonally expanded B-cell populations. Recent studies indicate that the complementarity determining regions of immunoglobulins specific for certain antigens are frequently shared between different individuals. In this study, our main objective was to identify specific proteomic profiles of mutated complementarity determining regions of immunoglobulin G present in multiple sclerosis patients but absent in healthy controls. To achieve this objective, we purified immunoglobulin G from the cerebrospinal fluid of 29 multiple sclerosis patients and 30 healthy controls and separated the corresponding heavy and light chains via SDS-PAGE. Subsequently, bands were excised, trypsinized, and measured with high-resolution mass spectrometry. We sequenced 841 heavy and 771 light chain variable region peptides. We observed 24 heavy and 26 light chain complementarity determining regions that were solely present in a number of multiple sclerosis patients. Using stringent criteria for the identification of common peptides, we found five complementarity determining regions shared in three or more patients and not in controls. Interestingly, one complementarity determining region with a single mutation was found in six patients. Additionally, one other patient carrying a similar complementarity determining region with another mutation was observed. In addition, we found a skew in the κ-to-λ ratio and in the usage of certain variable heavy regions that was previously observed at the transcriptome level. At the protein level, cerebrospinal fluid immunoglobulin G shares common characteristics in the antigen binding region among different multiple sclerosis patients. The indication of a shared fingerprint may indicate common antigens for B-cell activation.

  8. Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies

    PubMed Central

    Gustafson, R; Gardulf, A; Hansen, S; Leibl, H; Engl, W; Lindén, M; Müller, A; Hammarström, L

    2008-01-01

    Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy in patients with primary antibody deficiences (PAD) is being applied increasingly. However, only a few published pharmacokinetic studies are available for this route of administration. Therefore, the pharmacokinetics of a 16% immunoglobulin G (IgG) preparation intended for subcutaneous use were investigated in patients with common variable immunodeficiency and X-linked agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to 12 adult patients every 14 days for 24 weeks (total of 144 infusions). Pharmacokinetic parameters were determined based on serum IgG trough levels and antibody levels against tetanus. The median half-life of the total serum IgG and for the tetanus antibodies was 40·6 and 23·3 days respectively. Median in vivo recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively. Median, preinfusion serum IgG trough levels per patient were high without major variations between infusions and ranged from 7·24 to 7·86 g/l. Safety, in terms of adverse events including systemic adverse reactions and local tissue reactions at infusions sites, was monitored throughout the study. Six mild, local tissue reactions were observed during the study in one patient. No systemic adverse reactions related to the study drug were observed and no serious other adverse event occurred during the study. It is concluded that the bi-weekly SCIG therapy was well tolerated in the study and that it results in high and stable serum IgG levels, offering an alternative therapy regimen to patients suffering from PAD. PMID:18341618

  9. Developing therapeutic immunoglobulins: European regulatory perspectives and implications.

    PubMed

    Kurz, Manfred

    2008-01-01

    Prepared from pooled human blood/plasma, therapeutic immunoglobulins contain the natural antibody spectrum of the entire donor population and mediate a range of therapeutic effects when administered to patients. They are particularly indicated for the prevention of serious and life-threatening infections in patients with immune systems failing to produce functional antibodies. Other than treatment of such rare primary immunodeficiencies (primary antibody deficiencies), therapeutic immunoglobulins are also used in certain inflammatory and autoimmune disorders, including immune thrombocytopenic purpura, Guillain Barré syndrome, and Kawasaki disease. The conditions for licensure of therapeutic immunoglobulins in the EU and the associated regulatory issues and procedures are reviewed. Regulatory expectations about the manufacture and control of immunoglobulins are highlighted and safety and efficacy requirements described. Although the main focus is on European pharmaceutical legislation, other applicable public information is considered.

  10. 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.

  11. [The use of human immunoglobulins--adverse reactions].

    PubMed

    Pituch-Noworolska, Anna; Błaut-Szlósarczyk, Anita; Zwonarz, Katarzyna

    2010-09-01

    The primary immunodeficiency, mainly humoral immunity, secondary immunodeficiency and autoimmune diseases are the indications for immunoglobulins substitution. The prolonged substitution in primary immunodeficiency includes regular intravenous infusion of immunoglobulins in 0.4-0.6 g/kg of body weight every 21-28 days. The purpose of such substitution is decrease of frequency and diminishes the clinical course of infections. The high-dose use of immunoglobulins (1-2 g/kg body weight) is preferred in autoimmune diseases based on suppressive and anti-inflammatory activity of immunoglobulins. The subcutaneous administration of immunoglobulins is an alternative to intravenous way, but the singular dose (0.1 g/kg body weight) is too low for suppressive and anti-inflammatory activity of immunoglobulins, so this substitution is indicated in primary immunodeficiency only. The adverse events of immunoglobulins differentiate because of time of occurrence and clinical character. The rapid symptoms occurred just after beginning of infusion and often present the clinical features of anaphylactoid reaction. During the infusion the occurring adverse symptoms are mild and the life-threatening situations are very rare. The next periods of typical adverse reaction are 24-48 hrs after infusion, 72 hrs and later. The mechanisms leading to adverse reaction to immunoglobulins are based on presence of IgG dimmers, stimulating high production of pro-inflammatory cytokines by immunocompetent cells. High level of cytokines is associated with high fever, chills, flu-like symptoms, feeling malaise and sick. The reaction of anti-IgA antibodies present in patient serum with IgA in immunoglobulins preparation is responsible for moderate and severe adverse clinical symptoms. The late adverse events present the symptoms of aseptic meningo-encephalitis. In case of adverse events the stopping of infusion, additions saline/ glucose infusion, anti-histaminic drugs of I and II generation and steroids

  12. 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

  13. [Determination of serum immunoglobulins in asthmatic patients].

    PubMed

    Cabrera Jiménez, M; Valdés Sánchez, A F; Argüelles Sobrino, D; Gómez Echevarría, A H; Lastra Alfonso, G

    1989-01-01

    One hundred eighty one asthmatic patients were evaluated at the Allergy Consultation in Hermanos Ameijeiras Clinical Surgical Hospital. A case history was made for each of the patients, where the family background and personal history of allergy was collected; possible precipitating factors (such as inhalable, food, infectious, irritant, as well as climate factors) and physical and respiratory examinations. Serum immunoglobulin tests (by means of the ultramicroanalitic system (SUMA) and the rest of Igs: IgA, IgG, IgM by means of Mancini's simple radial immunodifusion method were made. Total eosinophil count was made to all of the patients in the study as well as serial studies of the faces. An increase in the IgE and IgM figures was found in asthmatic patients related to individual controls, and in relation to the normal figures for the adult population in our country. IgA and IgG determinations were normal both in the asthmatic and control groups, related to the standard figures.

  14. Immunoglobulin class-switch recombination deficiencies.

    PubMed

    Durandy, Anne; Kracker, Sven

    2012-07-30

    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.

  15. 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.

  16. 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.

  17. 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.

  18. Immunological studies of an atypical (myeloma) immunoglobulin

    PubMed Central

    Johansson, S. G. O.; Bennich, H.

    1967-01-01

    An 8S myeloma component, isolated from serum of a patient with myelomatosis is described, which appears to have no antigenic determinants in common with human, α-, δ-, γ- or μ-polypeptide chains as revealed by immuno-electrophoresis and Ouchterlony gel diffusion analysis. The myeloma protein migrates in the fast γ-region on electrophoresis at pH 8.6 and has an elution volume on Sephadex G-200 similar to that of 6.5S IgA. The isolated myeloma component has an approximate molecular weight of 200,000 and a total carbohydrate content of 10.7 per cent. Reduction with β-mercaptoethanol and acid dissociation yields light polypeptide chains of Type L and a carbohydrate-rich component, in the ratio of 1:4. Antisera specific to determinants on the heavy chains of the myeloma protein showed no reaction with the immunoglobulins A, D, G or M. Instead unique determinants were found on the heavy polypeptide chains. ImagesFIG. 3FIG. 1FIG. 7FIG. 9FIG. 10 PMID:4168094

  19. Autoantibodies and immunoglobulins in collagenous colitis.

    PubMed Central

    Bohr, J; Tysk, C; Yang, P; Danielsson, D; Järnerot, G

    1996-01-01

    BACKGROUND: The aetiology and pathogenesis of collagenous colitis are unknown. Autoimmunity has been suggested, but no serological findings have supported such a theory. AIMS AND METHODS: Serum from 38 collagenous colitis patients and 38 matched healthy controls was analysed for autoantibodies--that is, antinuclear antibodies, antineutrophil cytoplasmic antibodies, smooth muscle and mitochondrial antibodies, rheumatoid factor and antibodies to thyroglobulin and microsomal antigen, together with antibodies to endomysium, gliadin, and cardiolipin. The serum values of IgA, IgG, IgM, and IgG-subclasses, and complement factors C3 and C4 were also determined. RESULTS: In patients with collagenous colitis the mean value of IgM was significantly increased 2.5 g/l (95% CI; 1.9, 3.2) compared with 1.4 g/l (95% CI; 1.2, 1.7) in controls (p = 0.002). Antinuclear antibodies occurred in nine of 38 patients compared with three of 38 controls, this difference was not statistically significant (p = 0.11). The results of all other immunoglobulins, complement factors, and specific antibodies showed no statistical difference between patients and controls. CONCLUSIONS: No firm evidence for an autoimmune genesis in collagenous colitis is found in this study, although the findings of a positive ANA-titre in some patients and an increased IgM level might give some support for this hypothesis. PMID:8881813

  20. 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

  1. The new generation of liquid intravenous immunoglobulin formulations in patient care: a comparison of intravenous immunoglobulins.

    PubMed

    Stein, Mark R

    2010-09-01

    Intravenous immunoglobulin (IGIV) replacement therapy is the standard of care for primary immunodeficiencies with impaired humoral immunity. It is also the immunomodulatory therapy of choice for some types of neuroimmunologic and autoimmune hematologic disorders and for immunomodulation in bone marrow and some solid organ transplants. Currently available IGIV products include older lyophilized formulations, 5% liquid products, and newer, liquid, ready-to-use, 10% formulations. Differences in the formulations, manufacturing processes, excipients, pH, and other physicochemical properties of IGIV products may affect their clinical efficacy and tolerability. Among at-risk patients, the possibility of serious complications such as renal insufficiency, heart failure, thrombotic events, and immunological reactions may be increased if an IGIV formulation has sugar as a stabilizer, has high sodium or immunoglobulin A (IgA) content, or is hyperosmolar. The 10% liquid formulations may offer advantages because of their lower IgA concentrations, optimal pH, glycine or proline stabilizers, low sodium content, and lower osmolality. Liquid formulations are more convenient for patients and health care providers due to shorter infusion times and easier preparation and administration.

  2. Immunoglobulin negative follicle centre cell lymphoma.

    PubMed Central

    Gregg, E. O.; Al-Saffar, N.; Jones, D. B.; Wright, D. H.; Stevenson, F. K.; Smith, J. L.

    1984-01-01

    Immunoglobulin (Ig) could not be detected on the surface or in the cytoplasm of neoplastic cells from five cases of follicle centre cell lymphoma with centroblastic/centrocytic follicular histology when examined by immunohistology of frozen or wax embedded sections. Examination by fluorescein labelled antibodies of cells in suspensions prepared from the biopsies revealed a monotypic surface Ig positive population in one case and a surface or cytoplasmic Ig kappa:lambda light chain imbalance in a further two cases consistent with neoplastic B cell involvement: in all cases the proportion of cells failing to express Ig or T cell markers ranged from 24 to 75%. The monoclonal antibodies B1 (Pan B cell), FMC4 (HLA class II) and J5 (cALL antigen) stained the majority of cells in suspension with residual cells staining with UCHT1 or OKT11 (T cell monoclonal antibodies). In frozen sections, neoplastic follicular cells did not stain with UCHT1. However, in the one case tested these cells stained with the antibodies B1 and FMC4. In paraffin sections J chain could be demonstrated in the cytoplasm of three out of five cases. Cells from four cases were cultured in vitro for Ig production: two failed to produce Ig and monotypic light chains were the sole Ig product of the remaining two cases. The failure to express Ig by the majority of the neoplastic cells from the cases described in this report is at variance with the follicular histology of these neoplasms. Mechanisms responsible for this failure are discussed with reference to current models of B cell differentiation. Images Figure 1 PMID:6437429

  3. Immunoglobulin VH determinants defined by monoclonal antibodies

    PubMed Central

    1982-01-01

    Hybridoma clones secreting antibodies against common VH determinants were readily produced by fusion of cells from mice immunized with isolated V mu fragments of human immunoglobulins (Ig), but not with intact Ig molecules or isolated heavy chains. Four monoclonal antibodies to the V mu fragments of different IgM paraproteins were selected for analysis: MH-44 (mu kappa), GB-24 (mu kappa), NF-11 (gamma 1 kappa), and SA-44 (gamma 1 kappa). Each antibody reacted with the homologous V mu fragment, homologous mu chain, and normal gamma chains, but not with the intact IgM molecules, intact IgG, or isolated light chains, as determined by radioimmunoassay. The VH reaction spectra with a panel of myeloma heavy chains showed overlapping but distinctive patterns for the four antibodies. Each of the four monoclonal anti-VH antibodies appeared to react with a different "hidden" VH determinant that is not exposed on undenatured, intact Ig molecules and differs from conventional VH subgroup determinants. In immunofluorescence studies, the monoclonal anti-VH antibodies did not bind to surface Ig on viable B lymphocytes, but visibly stained subpopulations of fixed B lymphocytes, pre-B cells, and normal plasma cells. The mean frequencies of VH+ plasma cells were 30% (MH-44), 17% (GB-24), 13% (NF-11), and 3% (SA-44), and similar frequencies were obtained for the VH+ B cell subpopulations. While subpopulations of B cells could be identified at all stages in differentiation by immunofluorescence with the anti-VH antibodies, neither resting nor activated T cells expressed these VH determinants in detectable amounts. PMID:6185604

  4. Immunoglobulin heavy chains in medaka (Oryzias latipes)

    PubMed Central

    2011-01-01

    Background Bony fish present an immunological system, which evolved independently from those of animals that migrated to land 400 million years ago. The publication of whole genome sequences and the availability of several cDNA libraries for medaka (Oryzias latipes) permitted us to perform a thorough analysis of immunoglobulin heavy chains present in this teleost. Results We identified IgM and IgD coding ESTs, mainly in spleen, kidney and gills using published cDNA libraries but we did not find any sequence that coded for IgT or other heavy chain isotypes described in fish. The IgM - ESTs corresponded with the secreted and membrane forms and surprisingly, the latter form only presented two constant heavy chain domains. This is the first time that this short form of membrane IgM is described in a teleost. It is different from that identified in Notothenioid teleost because it does not present the typical splicing pattern of membrane IgM. The identified IgD-ESTs only present membrane transcripts, with Cμ1 and five Cδ exons. Furthermore, there are ESTs with sequences that do not have any VH which disrupt open reading frames. A scan of the medaka genome using transcripts and genomic short reads resulted in five zones within a region on chromosome 8 with Cμ and Cδ exons. Some of these exons do not form part of antibodies and were at times interspersed, suggesting a recombination process between zones. An analysis of the ESTs confirmed that no antibodies are expressed from zone 3. Conclusions Our results suggest that the IGH locus duplication is very common among teleosts, wherein the existence of a recombination process explains the sequence homology between them. PMID:21676244

  5. 7th International Immunoglobulin Conference: Immunomodulation

    PubMed Central

    Danieli, M G; Shoenfeld, Y

    2014-01-01

    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 [1-6]. 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. PMID:25546784

  6. Hyaluronidase facilitated subcutaneous immunoglobulin in primary immunodeficiency

    PubMed Central

    Jolles, Stephen

    2013-01-01

    Immunoglobulin (Ig)-replacement therapy represents the mainstay of treatment for patients with primary antibody deficiency and is administered either intravenously (IVIg) or subcutaneously (SCIg). While hyaluronidase has been used in clinical practice for over 50 years, the development of a high-purity recombinant form of this enzyme (recombinant human hyaluronidase PH20) has recently enabled the study of repeated and more prolonged use of hyaluronidase in facilitating the delivery of SC medicines. It has been used in a wide range of clinical settings to give antibiotics, local anesthetics, insulin, morphine, fluid replacement, and larger molecules, such as antibodies. Hyaluronidase has been used to help overcome the limitations on the maximum volume that can be delivered into the SC space by enabling dispersion of SCIg and its absorption into lymphatics. The rate of facilitated SCIg (fSCIg) infusion is equivalent to that of IVIg, and the volume administered at a single site can be greater than 700 mL, a huge increase over conventional SCIg, at 20–40 mL. The use of fSCIg avoids the higher incidence of systemic side effects of IVIg, and it has higher bioavailability than SCIg. Data on the long-term safety of this approach are currently lacking, as fSCIg has only recently become available. fSCIg may help several areas of patient management in primary antibody deficiency, and the extent to which it may be used in future will depend on long-term safety data and cost–benefit analysis. PMID:27471693

  7. 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

  8. Uninvolved immunoglobulins predicting hematological response in newly diagnosed AL amyloidosis.

    PubMed

    Muchtar, Eli; Magen, Hila; Itchaki, Gilad; Cohen, Amos; Rosenfeld, Ra'ama; Shochat, Tzippy; Kornowski, Ran; Iakobishvili, Zaza; Raanani, Pia

    2016-02-01

    Immunoparesis serves as a marker for elevated risk for progression in plasma cell proliferative disorders. However, the impact of immunoparesis in AL amyloidosis has not been addressed. Immunoparesis was defined qualitatively as any decrease below the low reference levels of the uninvolved immunoglobulins and quantitatively, as the relative difference between the uninvolved immunoglobulins and the lower reference values. Forty-one newly diagnosed AL amyloidosis patients were included. Sixty-six percent of patients had a suppression of the uninvolved immunoglobulins. The median relative difference of the uninvolved immunoglobulins was 18% above the low reference levels [range (-71%)-210%]. Ninety percent of the patients were treated with novel agents-based regimens, mostly bortezomib-containing regimens. Nineteen percent of the patients did not attain response to first line treatment. Patients with relative difference of uninvolved immunoglobulins below -25% of the low reference levels were less likely to respond to first line treatment compared to patients with a relative difference of -25% and above [odds ratio for no response vs. partial response and better 30 [(95% CI 4.1-222.2), P=0.0004]. Patients who failed first line treatment were successfully salvaged with lenalidomide-based treatment. Immunoparesis, if assessed quantitatively, may serve as a predictor of response in AL amyloidosis patients treated with bortezomib-containing regimens.

  9. Evolutionary Genomics of Immunoglobulin-Encoding Loci in Vertebrates

    PubMed Central

    Das, Sabyasachi; Hirano, Masayuki; Tako, Rea; McCallister, Chelsea; Nikolaidis, Nikolas

    2012-01-01

    Immunoglobulins (or antibodies) are an essential element of the jawed vertebrate adaptive immune response system. These molecules have evolved over the past 500 million years and generated highly specialized proteins that recognize an extraordinarily large number of diverse substances, collectively known as antigens. During vertebrate evolution the diversification of the immunoglobulin-encoding loci resulted in differences in the genomic organization, gene content, and ratio of functional genes and pseudogenes. The tinkering process in the immunoglobulin-encoding loci often gave rise to lineage-specific characteristics that were formed by selection to increase species adaptation and fitness. Immunoglobulin loci and their encoded antibodies have been shaped repeatedly by contrasting evolutionary forces, either to conserve the prototypic structure and mechanism of action or to generate alternative and diversified structures and modes of function. Moreover, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, which are used by different species to effectively generate an almost infinite collection of diverse antibody types. This review summarizes our current knowledge on the genomics and evolution of the immunoglobulin-encoding loci and their protein products in jawed vertebrates. PMID:23024601

  10. Epigallocatechin-3-gallate preferentially induces aggregation of amyloidogenic immunoglobulin light chains

    PubMed Central

    Hora, Manuel; Carballo-Pacheco, Martin; Weber, Benedikt; Morris, Vanessa K.; Wittkopf, Antje; Buchner, Johannes; Strodel, Birgit; Reif, Bernd

    2017-01-01

    Antibody light chain amyloidosis is a rare disease caused by fibril formation of secreted immunoglobulin light chains (LCs). The huge variety of antibody sequences puts a serious challenge to drug discovery. The green tea polyphenol epigallocatechin-3-gallate (EGCG) is known to interfere with fibril formation in general. Here we present solution- and solid-state NMR studies as well as MD simulations to characterise the interaction of EGCG with LC variable domains. We identified two distinct EGCG binding sites, both of which include a proline as an important recognition element. The binding sites were confirmed by site-directed mutagenesis and solid-state NMR analysis. The EGCG-induced protein complexes are unstructured. We propose a general mechanistic model for EGCG binding to a conserved site in LCs. We find that EGCG reacts selectively with amyloidogenic mutants. This makes this compound a promising lead structure, that can handle the immense sequence variability of antibody LCs. PMID:28128355

  11. Concurrent Drug-Induced Linear Immunoglobulin A Dermatosis and Immunoglobulin A Nephropathy.

    PubMed

    Kim, Ji Seok; Choi, Misoo; Nam, Chan Hee; Kim, Jee Young; Park, Byung Cheol; Kim, Myung Hwa; Hong, Seung Phil

    2015-06-01

    Diseases associated with immunoglobulin A (IgA) antibody include linear IgA dermatosis, IgA nephropathy, Celiac disease, Henoch-Schönlein purpura, etc. Although usually idiopathic, IgA antibody is occasionally induced by drugs (e.g., vancomycin, carbamazepine, ceftriaxone, and cyclosporine), malignancies, infections, and other causes. So far, only a few cases of IgA bullous dermatosis coexisting with IgA nephropathy have been reported. A 64-year-old female receiving intravenous ceftriaxone and metronidazole for liver abscess had purpuric macules and papules on her extremities. One week later, she had generalized edema and skin rash with bullae and was diagnosed with concurrent linear IgA dermatosis and IgA nephropathy. After steroid treatment, the skin lesion subsided within two weeks, and kidney function slowly returned to normal. As both diseases occurred after a common possible cause, we predict their pathogeneses are associated.

  12. Interference of immunoglobulins in two glucagon radioimmunoassays. [Blood donor and patient immunoglobulins

    SciTech Connect

    Von Schenck, H.; Grubb, A.O.

    1982-05-01

    Radioimmunoassays of glucagon in plasma may be complicated by interaction with other substances of high molecular mass. Precipitates of such substances with ammonium sulfate showed, after isoelectric focusing, two fractions having glucagon immunoreactivity. One fraction (pI approx.10) evidently is associated with the Fc portion (but not the Fab portion) of purified polyclonal immunoglobulin G (IgG). Equal amounts of purified monoclonal IgG of various subclasses, especially IgG 1, gave different ''glucagon'' readings, suggesting that some IgG may interfere more strongly than others. The other fraction (pI 5-6) appeared less consistently, and on gel chromatography appeared to be slightly larger than IgG. Together these fractions add about 50-100 ng/L to the immunoreactive glucagon values in plasma. Therefore methods in which glucagon is extracted before assay should be used for determining the concentration of glucagon present physiologically.

  13. Russell body inducing threshold depends on the variable domain sequences of individual human IgG clones and the cellular protein homeostasis.

    PubMed

    Stoops, Janelle; Byrd, Samantha; Hasegawa, Haruki

    2012-10-01

    Russell bodies are intracellular aggregates of immunoglobulins. Although the mechanism of Russell body biogenesis has been extensively studied by using truncated mutant heavy chains, the importance of the variable domain sequences in this process and in immunoglobulin biosynthesis remains largely unknown. Using a panel of structurally and functionally normal human immunoglobulin Gs, we show that individual immunoglobulin G clones possess distinctive Russell body inducing propensities that can surface differently under normal and abnormal cellular conditions. Russell body inducing predisposition unique to each immunoglobulin G clone was corroborated by the intrinsic physicochemical properties encoded in the heavy chain variable domain/light chain variable domain sequence combinations that define each immunoglobulin G clone. While the sequence based intrinsic factors predispose certain immunoglobulin G clones to be more prone to induce Russell bodies, extrinsic factors such as stressful cell culture conditions also play roles in unmasking Russell body propensity from immunoglobulin G clones that are normally refractory to developing Russell bodies. By taking advantage of heterologous expression systems, we dissected the roles of individual subunit chains in Russell body formation and examined the effect of non-cognate subunit chain pair co-expression on Russell body forming propensity. The results suggest that the properties embedded in the variable domain of individual light chain clones and their compatibility with the partnering heavy chain variable domain sequences underscore the efficiency of immunoglobulin G biosynthesis, the threshold for Russell body induction, and the level of immunoglobulin G secretion. We propose that an interplay between the unique properties encoded in variable domain sequences and the state of protein homeostasis determines whether an immunoglobulin G expressing cell will develop the Russell body phenotype in a dynamic cellular setting.

  14. Intravenous and subcutaneous immunoglobulin G replacement therapy.

    PubMed

    Bonilla, Francisco A

    2016-11-01

    Human polyclonal immunoglobulin G (IgG) for therapeutic use has been available for decades. This drug was developed for treatment of antibody deficiency (replacement therapy), although its use has expanded into many anti-inflammatory and immunomodulatory applications in recent years. This review focuses on IgG prescribing for replacement therapy. IgG for replacement is most often administered via the intravenous IgG (IVIG) or subcutaneous IgG (SCIG) routes. IVIG is usually administered every 34 weeks, and SCIG is usually administered weekly, although variations may be considered in all cases. Recently, a new product became available that uses hyaluronidase to facilitate absorption of large doses of SCIG less frequently (every 34 weeks, as with IVIG). There are important differences between the pharmacokinetics of these three routes of administration. IVIG therapy leads to high peaks and low troughs between infusions. IgG concentration fluctuates much less over time with SCIG. Hyaluronidase-facilitated SCIG is intermediate. SCIG may have lower bioavailability in comparison with IVIG and may require higher doses over time; this is not true for hyaluronidase SCIG. However, there are large variations in IgG half-life among individuals and with different products. Therefore, individualization of therapy is essential. Mild systemic flu-like adverse effects may affect up to 2025% of patients who receive IVIG, smaller fractions may experience more-severe symptoms, whereas anaphylaxis is exceedingly rare. General flu-like systemic adverse effects are minimal with SCIG (intermediate with hyaluronidase SCIG), but transient (24 hours), mild, local inflammatory symptoms at infusion sites are relatively common with both forms. Additional rare but important complications of IgG therapy include thrombotic events and hemolysis that can be seen at high doses with any route of administration. Renal adverse effects may occur with IVIG as well. The variety of IgG products and routes of

  15. 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

  16. 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

    2016-02-15

    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.

  17. 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

  18. Quantitative levels of immunoglobulin E in advanced tuberculosis.

    PubMed

    Casterline, C L; Evans, R; Ward, G W

    1976-07-01

    Quantitative levels of immunoglobulin E (IgE) were determined in samples of sera obtained from 29 patients with proven moderate to far-advanced tuberculosis. The sensitive radioimmunoassay test for IgE was used. Statistical analysis of the results revealed no difference in IgE values as compared to a control group of normal sera. In contrast to other chronic pulmonary infections, such as bronchopulmonary aspergillosis, the IgE level in pulmonary tuberculous infection is of no diagnostic significance. Simultaneous determination of levels of immunoglobulins G, A, M, and D (IgG, IgA, IgM, IgD) in these same sera by radial immunodiffusion showed elevated IgG and lowered IgM levels in the tuberculous patients, confirming previous studies. The significance of these alterations in immunoglobulin levels is unclear and may represent a secondary phenomenon rather than a primary host response.

  19. The binding of immunoglobulin Fc to cationic proteins.

    PubMed Central

    Pambakian, S; Poston, R N

    1987-01-01

    The interaction of cationic proteins with IgG, IgA and IgM were investigated by solid phase radioimmunoassay. All these immunoglobulins showed avid binding, IgM giving the strongest reaction, followed by IgA and then IgG. Fc fragments of IgG gave binding, but F(ab')2 fragments from the three main Ig classes did not, showing that the Fc region is the active part of the molecule. The effects of changes of ionic strength and pH are compatible with the interaction being ionic, and are similar to those seen between immunoglobulins and both Clq and cationic ion exchange gels. The addition of other serum proteins resulted in marked inhibition of the interaction. These phenomena are likely to have fundamental significance for the understanding of interactions of immunoglobulins in vivo and in vitro. Images Fig. 6 PMID:3652520

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

    PubMed

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

    2015-08-24

    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.

  1. 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.

  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. Transfer of antibodies across the placenta and in breast milk from mothers on intravenous immunoglobulin.

    PubMed

    Palmeira, Patricia; Costa-Carvalho, Beatriz T; Arslanian, Christina; Pontes, Gerlândia N; Nagao, Aparecida T; Carneiro-Sampaio, Magda M S

    2009-09-01

    We studied the levels of immunoglobulins in colostrum, milk and sera from two common variable immunodeficiency (CVID) mothers (M1 and M2), and in sera from their newborn infants. During pregnancy they continued intravenous immunoglobulin therapy (IVIG). Antibody levels from maternal and cord blood collected at delivery and colostrum and milk, collected on the 3rd and 7th post-partum days, respectively, were analyzed. Although cord/maternal blood ratios of total immunoglobulins and subclasses, as well as specific antibodies differed between M1 and M2, both showed good placental transfer of anti-protein and anti-polysaccharide antibodies, despite lower cord/maternal blood ratios in M2. Anti-Streptococcus pneumoniae antibody avidity indexes were similar between paired maternal and cord serum. Both mothers' colostrum and milk samples showed only traces of IgA, and IgM and IgG levels in colostrum were within normal range in M1, whereas M2 presented elevated IgG and low IgM levels, when compared with healthy mothers. The study of colostrum and milk activity showed that they strongly inhibited enteropathogenic Escherichia coli adhesion in vitro. CVID patients must be informed about the relevance of regular IVIG administration during pregnancy, not only for their own health but also for their immune immature offspring. Breast-feeding should be encouraged as colostra from these CVID patients strongly inhibited E. coli adhesion to human epithelial cells thus providing immunological protection plus nutritional and psychological benefits for the infant.

  4. Immunoglobulin M Nephropathy in a Patient with Wilson's Disease.

    PubMed

    Ul Abideen, Zain; Sajjad, Zoya; Haroon Khan, Asna; Mamoon, Nadira; Bilal, Muhammad; Mujtaba Quadri, Khaja Hameeduddin

    2016-12-13

    Immunoglobulin M nephropathy (IgMN) is characterized by the deposition of immunoglobulin M in a dominant distribution in the renal glomeruli. Primary immunoglobulin M nephropathy is diagnosed after consistent light microscopy (LM), immunofluorescence (IF), electron microscopy (EM) results, and exclusion of known systemic disorders causing immunoglobulin M deposition in the glomeruli. The secondary disease has been reported with a few conditions though it has never been reported with any primary disease of the liver. We report the case of an adolescent male patient who presented with nausea, vomiting, diarrhea, and worsening anasarca. He was found to have nephrotic-range proteinuria that did not respond to conventional corticosteroid treatment. He was subjected to a renal biopsy which revealed a diagnosis of immunoglobulin M nephropathy. His liver function tests were deranged and an ultrasound scan of the abdomen revealed a coarse irregular liver. Workup revealed elevated urine copper excretion and a low ceruloplasmin level. He was diagnosed as a case of Wilson's disease and started on penicillamine and pyridoxine. He was also started on intravenous cyclophosphamide for the corticosteroid-resistant nephrotic syndrome to which he responded remarkably well. His edema settled, proteinuria resolved, and liver functions normalized. Currently, he is in remission and enjoying good health. To the best of our knowledge, we report the first known association between IgM nephropathy and Wilson's disease. It is presently not clear if causation can necessarily be established. This may be the result of defective IgM clearance by the liver or an altered metabolism of the antibody or immune complexes, as with hepatic-associated immunoglobulin M (IgM) nephropathy. Further studies are needed to elucidate the exact mechanism of this disease.

  5. 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.

  6. Russell body duodenitis with immunoglobulin kappa light chain restriction.

    PubMed

    Munday, William R; Kapur, Lucy Harn; Xu, Mina; Zhang, Xuchen

    2015-01-16

    Russell bodies are eosinophilic intracytoplasmic globules which are likely the result of disturbed secretion of immunoglobulins that accumulate within the plasma cell. Russell body collections have been identified within the stomach, known as Russell body gastritis. Similar lesions within the duodenum are referred to as Russell body duodenitis, which is rare. Several Russell body gastritis case reports are associated with Helicobacter pylori. However, the etiology of Russell body duodenitis remains unclear. Here we report the first case of Russell body duodenitis with immunoglobulin light chain restriction in a background of peptic duodenitis.

  7. The patient: Emerging clinical applications of intravenous immunoglobulin.

    PubMed

    Harvey, R Donald

    2005-11-01

    Intravenous immunoglobulin (IGIV) originally was used as prophylactic treatment of infections in patients with primary immunodeficiency disease. Today, administration of IGIV, due in large part to its immunomodulatory activity, has expanded to include a number of other disorders. Available data suggest that the accepted indications for IGIV will continue to expand. As the number of clinical applications for this therapy grows, so will market opportunities; current preparations will be modified and improved and new products introduced. Intravenous immunoglobulin therapy has improved the lives of many patients with immune-related disorders. Future applications will ideally advance this paradigm further.

  8. 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....

  9. 21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... immunoglobulin G (resulting from breakdown of immunoglobulin G antibodies) in urine, serum, and other body fluids... abnormalities, e.g., gamma heavy chain disease. (b) Classification. Class I (general controls). The device...

  10. Distribution of maternal immunoglobulins in the mouse uterus and embryo in the days after implantation

    PubMed Central

    1977-01-01

    The distribution of maternal immunoglobulins in the mouse uterus and embryo in the days after implantation has been studied on sections incubated with sheep Fab anti-mouse immunoglobulins labeled with peroxidase. At the time of implantation the blastocyst is already surrounded by immunoglobulins that are also present in the blastocoel and early endoderm; uterine glands contain large amounts of immunoglobulins. Later, immunoglobulins are concentrated in the vacuolated endoderm, then the visceral yolk sac and the embryonic gut. They are also present in the various cavities of the embryo. Trophoblast cells progressively contain increasing amounts of immunoglobulins. In the decidua, immunoglobulins coat the cells and also occasionally appear as cytoplasmic granules. The early presence of maternal immunoglobulins may represent the transfer of serum proteins as a means of nutrition for the embryo. It is also very likely to have an immunological significance in the protection of the embryo. PMID:830790

  11. An update on the use of immunoglobulin for the treatment of immunodeficiency disorders

    PubMed Central

    Albin, Stephanie; Cunningham-Rundles, Charlotte

    2015-01-01

    For patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement. PMID:25428649

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

    PubMed

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

    2014-09-01

    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.

  13. A microtiter solid-phase radioimmunoassay for platelet-associated immunoglobulin G

    SciTech Connect

    Cheung, N.V.; McFall, P.; Schulman, I.

    1983-03-01

    An MSPRIA is described for measuring platelet-associated immunoglobulins by competitive inhibition of the binding of radiolabeled goat anti-human class-specific antibody to solid-phase immunoglobulins. PAIgG can be estimated from calibration curves constructed from soluble IgG inhibitors. The MSPRIA for IgG is antibody class-specific. The coefficient of variability is between 6% and 20%. The MSPRIA is more sensitive than other described assays. Comparative studies demonstrated that ACD-A is the preferred anticoagulant for collecting platelets for the MSPRIA and that sonicated platelets are more reliable than intact platelets in demonstrating elevated PAIgG in immune thrombocytopenias. Intact platelets from 18 normal volunteers had PAIgG ranging from 0.4 to 3.3 fg/platelet (mean +/- S.D. = 1.5 +/- 1). The same platelets when sonicated had a mean +/- S.D. PAIgG of 3.3 +/- 1 fg/platelet, with a range of 1 to 5. Only 60% of 30 adult ITP patients with presumed immune thrombocytopenia had elevated PAIgG levels when their intact platelets were studied. When these same platelets were sonicated, 87% of them had abnormal levels of PAIgG.

  14. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulins A, G, M, D, and E immunological... Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of...

  15. Stability of orally administered immunoglobulin in the gastrointestinal tract.

    PubMed

    Lee, Jeongmin; Kang, Hae-Eun; Woo, Hee-Jong

    2012-10-31

    Oral administration of immunoglobulin in the colostrum or egg yolk has been considered an effective tool for preventing enterobacterial infection via passive immunization. During this process, the transmission and residence of the active immunoglobulin are the most important conditions for successful protection. We investigated the stability of encapsulated colostrum and egg yolk immunoglobulin for the effective transmission of immunoglobulin in the gastrointestinal (GI) tract. First, we measured GI transit time. Contrast media passed through and reached the stomach within 10 min, the small intestine within 3.5 h, and the cecum within 5 h. Both the encapsulated colostrum containing anti-hepatitis A virus (HAV) antibody (IgG) and egg yolk with anti-rotavirus antibody (IgY) showed lower antibody activity than the non-encapsulated colostrum did in the stomach after administration; however, significantly higher antibody activities were observed in the encapsulated groups than in the non-encapsulated groups in the small intestine 3.5 h after the administration. In the large intestine, the antibody activities of the encapsulated groups were maintained or slightly increased in a time-dependent manner; however, the titers of each non-capsulated control were as low as the negative controls. Therefore, this encapsulation is considered a useful tool for the delivery of active antibody through the GI tract.

  16. A case of dermatomyositis with rhabdomyolysis, rescued by intravenous immunoglobulin.

    PubMed

    Mizoguchi, Fumitaka; Takada, Kazuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Kohsaka, Hitoshi; Miyasaka, Nobuyuki

    2015-07-01

    We describe a case of severe dermatomyositis (DM) complicated by rhabdomyolysis, acute tubular necrosis, and hemophagocytosis. The case failed to respond to corticosteroids, but showed rapid and significant improvement after the addition of intravenous immunoglobulin (IVIG). While the prognosis of DM is poor when it is complicated by rhabdomyolysis, the early administration of IVIG has the potential to be the cornerstone of its management.

  17. A case of immunoglobulin G4-related constrictive pericarditis

    PubMed Central

    Luo, Wen-Qi; Fang, Fang; Zhen, Wen-Jun; Ouyang, Xiao-Kang; Wang, Huai-Bin; Wang, Zi

    2016-01-01

    A 47-year-old man was admitted with a complaint of upper abdominal distension and shortness of breath. The constrictive pericarditis was diagnosed based on the transthoracic echocardiogram (TTE) and chest CT scan. Pathology revealed it is immunoglobulin (Ig) G4-related constrictive pericarditis. Likely, this is the first case of IgG4-related constrictive pericarditis reported in China. PMID:26904579

  18. Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis.

    PubMed

    Guptill, Jeffrey T; Juel, Vern C; Massey, Janice M; Anderson, Amanda C; Chopra, Manisha; Yi, John S; Esfandiari, Ehsanollah; Buchanan, Tim; Smith, Bryan; Atherfold, Paul; Jones, Emma; Howard, James F

    2016-11-01

    An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (∼60-70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG.

  19. Mucosal immunoglobulins and B cells of teleost fish.

    PubMed

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

    2011-12-01

    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 naïve 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.

  20. 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

  1. The immunoglobulin heavy chain locus in the platypus (Ornithorhynchus anatinus).

    PubMed

    Gambón-Deza, F; Sánchez-Espinel, C; Magadán-Mompó, S

    2009-08-01

    Immunoglobulins loci in mammals are well known to be organized within a translocon, however their origin remains unresolved. Four of the five classes of immunoglobulins described in humans and rodents (immunoglobulins M, G, E and A-IgM, IgG, IgE and IgA) were found in marsupials and monotremes (immunoglobulin D-IgD was not found) thus showing that the genomic structure of antibodies in mammals has remained constant since its origin. We have recently described the genomic organization of the immunoglobulin heavy chain locus in reptiles (IGHM, IGHD and IGHY). These data and the characterization of the IGH locus in platypus (Ornithorhynchus anatinus), allow us to elucidate the changes that took place in this genomic region during evolution from reptile to mammal. Thus, by using available genome data, we were able to detect that platypus IGH locus contains reptilian and mammalian genes. Besides having an IGHD that is very similar to the one in reptiles and an IGHY, they also present the mammal specific antibody genes IGHG and IGHE, in addition to IGHA. We also detected a pseudogene that originated by recombination between the IGHD and the IGHM (similar to the IGHD2 found in Eublepharis macularius). The analysis of the IGH locus in platypus shows that IGHY was duplicated, firstly by evolving into IGHE and then into IGHG. The IGHA of the platypus has a complex origin, and probably arose by a process of recombination between the IGHM and the IGHY. We detected about 44 VH genes (25 were already described), most of which comprise a single group. When we compared these VH genes with those described in Anolis carolinensis, we find that there is an evolutionary relationship between the VH genes of platypus and the reptilian Group III genes. These results suggest that a fast VH turnover took place in platypus and this gave rise to a family with a high VH gene number and the disappearance of the earlier VH families.

  2. Linear immunoglobulin A/immunoglobulin G bullous dermatosis associated with Vogt-Koyanagi-Harada disease.

    PubMed

    Yanagihara, Shigeto; Mizuno, Nobuyuki; Naruse, Akiko; Tateishi, Chiharu; Tsuruta, Daisuke; Ishii, Masamitsu

    2011-08-01

    Vogt-Koyanagi-Harada disease is characterized by marked bilateral uveitis associated with symmetric vitiligo, alopecia, poliosis and dysacousia. Linear immunoglobulin (Ig)A bullous dermatosis (LABD) is characterized by small, tense, subepidermal bullae caused by IgA type autoantibody targeting the basal lamina. LABD patients sometimes show coexistence of IgG type autoantibody, termed linear IgA/IgG bullous dermatosis (LAGBD). We reported a 35-year-old Japanese male case of combined LAGBD and Vogt-Koyanagi-Harada disease. His human leukocyte antigen typing was -A24, B52, C*1202, DR*1502, DQ*0601. Immunoblot revealed that patient sera reacted to both 180- and 230-kDa proteins at the IgA and IgG level. Because Vogt-Koyanagi-Harada disease and LABD are reported to be associated with other autoimmune diseases, it is probable that Vogt-Koyanagi-Harada disease and LAGBD in our case may be associated with each other in the pathomechanism. However, we cannot exclude the possibility of this being mere coincidence.

  3. 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

  4. 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.

  5. Influence of experimental alcohol administration on serum immunoglobulin levels: contrasting effects on IgE and other immunoglobulin classes.

    PubMed

    Alonso, M; Gomez-Rial, J; Gude, F; Vidal, C; Gonzalez-Quintela, A

    2012-01-01

    In humans, alcoholic liver disease is associated with hypergammaglobulinemia, particularly with high serum concentrations of IgA. Furthermore, alcohol consumption is associated with high concentrations of IgE and low concentrations of IgG. However, there is little experimental evidence to corroborate these observational findings. The objective of the present study was to investigate the potential short-term effects of alcohol administration on serum immunoglobulin concentrations in mice, and the potential influence of sex and strain on these effects. Eight mouse groups were defined by strain (Swiss vs C57BL/6), sex (male vs female), and experimental procedure (alcohol administration vs control diet). Alcohol was administered in a semi-liquid diet (6.5%v/v); control animals received an isocaloric semi-liquid diet. Immunoglobulin concentrations (IgE, IgA, IgM, IgG1, IgG2a, IgG2b, and IgG3) were measured at baseline and weekly thereafter for 4 weeks. Serum Th1 (interferon-gamma) and Th2 (IL-4 and IL-13) cytokines were measured at week 4. We found significant variations in baseline immunoglobulin concentrations depending upon mouse sex and strain. Alcohol administration was quickly followed by an increase in serum IgE concentrations in all experimental groups. IgE increase was correlated with serum IL-13 increase. In contrast, alcohol administration was not associated with significant changes in serum IgA and IgM concentration, and appeared to decrease IgG subclass concentrations. Alcohol effects on immunoglobulin concentrations were independent of mouse strain and sex. In conclusion, alcohol administration in mice had contrasting effects on IgE and other immunoglobulin classes. This experimental evidence confirms observational results in humans.

  6. 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.

  7. Genomic and functional characterization of the diverse immunoglobulin domain-containing protein (DICP) family

    PubMed Central

    Haire, Robert N.; Cannon, John P.; O’Driscoll, Marci L.; Ostrov, David A.; Mueller, M. Gail; Turner, Poem M.; Litman, Ronda T.; Litman, Gary W.; Yoder, Jeffrey A.

    2012-01-01

    A heretofore-unrecognized multigene family encoding diverse immunoglobulin (Ig) domain-containing proteins (DICPs) was identified in the zebrafish genome. Twenty-nine distinct loci mapping to three chromosomal regions encode receptor-type structures possessing two classes of Ig ectodomains (D1 and D2). The sequence and number of Ig domains, transmembrane regions and signaling motifs varies between DICPs. Interindividual polymorphism and alternative RNA processing contribute to DICP diversity. Molecular models indicate that most D1 domains are of the variable (V) type; D2 domains are Ig-like. Sequence differences between D1 domains are concentrated in hypervariable regions on the front sheet strands of the Ig fold. Recombinant DICP Ig domains bind lipids, a property shared by mammalian CD300 and TREM family members. These findings suggest that novel multigene families encoding diversified immune receptors have arisen in different vertebrate lineages and effect parallel patterns of ligand recognition that potentially impact species-specific advantages. PMID:22386706

  8. Multiple DNA sequence elements are necessary for the function of an immunoglobulin heavy chain promoter.

    PubMed Central

    Eaton, S; Calame, K

    1987-01-01

    Sequences required for the function of the mouse V1 immunoglobulin heavy chain variable-region (VH) promoter were identified by transient transfection of the normal and mutated promoters into plasmacytoma cells. Our results identify four regions required for normal promoter function: (i) the octamer ATGCAAAT, previously identified by others; (ii) a heptamer, CTAATGA; (iii) a pyrimidine-rich region; and (iv) a region between positions -125 and -251 relative to the transcription start site. Sequence analysis of 19 mouse and human VH 5' flanking regions shows that the heptamer and pyrimidine stretch are strongly conserved. We have also demonstrated that the octamer functions in an orientation independent manner in the VH promoter. Images PMID:3118372

  9. Site-specific photobiotinylation of antibodies, light chains, and immunoglobulin fragments.

    PubMed

    Pavlinkova, G; Lou, D; Kohler, H

    2000-09-01

    The high affinity of biotin for avidin has been exploited for many antibody-based assays. This requires that biotin is covalently conjugated to the antibody molecule. Several chemically reactive biotinylation reagents are commercially available. Except for the attachment via sulfhydryl groups in the immunoglobulin (Ig) molecule, these reagents attach biotin randomly to various amino acid side chains. Although non-site-specific modification of antibodies does not interfere in most immunoassays, specific application and sensitive antibodies would benefit from site-specific biotinylation. Here we describe an affinity biotinylation technique based on a photoreactive biotin reagent. The design of this reaction was possible from the discovery of a conserved binding site in the variable Ig domain for nucleotides and nucleosides. The described photoaffinity biotinylation offers the advantages of ease, convenience, and production of a reproducible and defined biotinylated antibody preparation.

  10. Notes on individual sequence variation in humans: Immunoglobulin kappa light chain

    SciTech Connect

    Kurth, J.H. ); Cavalli-Sforza, L.L. )

    1994-06-01

    Little is known concerning the magnitude of variability in the nucleic acid sequence of DNA at the individual level. The authors have collected a large set of sequence data from the human immunoglobulin kappa light-chain-locus constant region (10,444 bp) and subgroup IV variable region (18,580 bp). For the constant region, absolute conservation of sequence was observed, even in intron and coding-region silent sites, with the exception of one previously defined polymorphic site. For the variable region, 12 heterozygous positions were identified, giving a heterozygosity of 6 x 10[sup [minus]4] per nucleotide site. The amount of nucleic acid sequence variation differs significantly ([chi][sup 2] = 4.88) between these two regions, and the observed variation is two orders of magnitude lower than that reported for two Drosophila melanogaster loci. These data suggest that, for at least some regions of the human genome, nucleic acid sequence may be less variable than previously estimated. 13 refs., 2 figs.

  11. Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits complicated by immunoglobulin A nephropathy in the renal allograft.

    PubMed

    Sawada, Anri; Kawanishi, Kunio; Horita, Shigeru; Koike, Junki; Honda, Kazuho; Ochi, Ayami; Komoda, Mizuki; Tanaka, Yoichiro; Unagami, Kohei; Okumi, Masayoshi; Shimizu, Tomokazu; Ishida, Hideki; Tanabe, Kazunari; Nagashima, Yoji; Nitta, Kosaku

    2016-07-01

    Immunoglobulin (Ig) A nephropathy (IgAN) is a known autoimmune disease due to abnormal glycosylation of IgA1, and occasionally, IgG co-deposition occurs. The prognosis of IgG co-deposition with IgAN is adverse, as shown in the previous studies. However, in the clinical setting, monoclonality of IgG co-deposition with IgAN has not been observed. We describe a case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) combined with IgAN in a renal allograft. A-21-year-old man developed end-stage renal failure with unknown aetiology and underwent living-donor kidney transplantation from his mother 2 years after being diagnosed. One year after kidney transplantation, proteinuria 2+ and haematuria 2+ were detected; allograft biopsy revealed mesangial IgA and C3 deposits, indicating a diagnosis of IgAN. After tonsillectomy and steroid pulse therapy, proteinuria and haematuria resolved. However, 4 years after transplantation, pedal oedema, proteinuria (6.89 g/day) and allograft dysfunction (serum creatinine (sCr) 203.3 µmol/L) appeared. A second allograft biopsy showed mesangial expansion and focal segmental proliferative endocapillary lesions with IgA1λ and monoclonal IgG1κ depositions. Electron microscopic analysis revealed a massive amount of deposits, located in the mesangial and subendothelial lesions. A diagnosis of PGNMID complicated with IgAN was made, and rituximab and plasmapheresis were added to steroid pulse therapy. With this treatment, proteinuria was alleviated to 0.5 g/day, and the allograft dysfunction recovered to sCr 132.6 µmol/L. This case suggests a necessity for investigation of PGNMID and IgA nephropathy in renal allografts to detect monoclonal Ig deposition disease.

  12. Renal involvement of monoclonal immunoglobulin deposition disease associated with an unusual monoclonal immunoglobulin A glycan profile.

    PubMed

    Kaneko, Syuzou; Usui, Joichi; Narimatsu, Yoshiki; Ito, Hiromi; Narimatsu, Hisashi; Hagiwara, Masahiro; Tsuruoka, Shuichi; Nagata, Michio; Yamagata, Kunihiro

    2010-08-01

    A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-kappa gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-kappa deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient's serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-kappa staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient's serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.

  13. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    PubMed

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment.

  14. Immunoglobulin concentrations in human tears in ocular diseases.

    PubMed

    Sen, D K; Sarin, G S

    1979-05-01

    Immunoglobulin concentrations in human tears were determined in 165 patients with different eye diseases by a standard radial immunodiffusion method. IgA was present in all the samples in measurable quantity. The mean IgA values were significantly higher than the controls in patients with acute bacterial conjunctivitis, keratomalacia, corneal graft reaction, blepharoconjunctivitis, and acute keratoconjunctivitis. The values in the patients with vernal conjunctivitis, phlyctenular conjunctivitis, acute bacterial corneal ulcer, and acute endogenous uveitis were not significantly different from those in the controls. IgG could be detected in the majority of the samples but it was in measurable quantity in 18 samples. IgM could be detected in fewer samples. IgD was not detected in any of them. The study indicates that, whenever the immunoglobulin levels in tears are altered in diseased eyes, it is the IgA level that is predominantly altered and not the IgG level.

  15. Fc glycan-modulated immunoglobulin G effector functions.

    PubMed

    Quast, Isaak; Lünemann, Jan D

    2014-07-01

    Immunoglobulin G (IgG) molecules are glycoproteins and residues in the sugar moiety attached to the IgG constant fragment (Fc) are essential for IgG functionality such as binding to cellular Fc receptors and complement activation. The core of this sugar moiety consists of a bi-antennary heptameric structure of mannose and N-acetylglucosamine (GlcNAc), further decorated with terminal and branching residues including galactose, sialic acid, fucose, and GlcNAc. Presence or absence of distinct residues such as fucose and sialic acid can dramatically alter pro- and anti-inflammatory IgG activities which could be harnessed for immunotherapeutic purposes. Here we review recent advances in understanding the role of the IgG-Fc glycan during immune responses and for immunotherapy with a focus on sialic acid and intravenous immunoglobulin (IVIG) treatment.

  16. Of ITIMs, ITAMs, and ITAMis: revisiting immunoglobulin Fc receptor signaling.

    PubMed

    Getahun, Andrew; Cambier, John C

    2015-11-01

    Receptors for immunoglobulin Fc regions play multiple critical roles in the immune system, mediating functions as diverse as phagocytosis, triggering degranulation of basophils and mast cells, promoting immunoglobulin class switching, and preventing excessive activation. Transmembrane signaling associated with these functions is mediated primarily by two amino acid sequence motifs, ITAMs (immunoreceptor tyrosine-based activation motifs) and ITIMs (immunoreceptor tyrosine-based inhibition motifs) that act as the receptors' interface with activating and inhibitory signaling pathways, respectively. While ITAMs mobilize activating tyrosine kinases and their consorts, ITIMs mobilize opposing tyrosine and inositol-lipid phosphatases. In this review, we will discuss our current understanding of signaling by these receptors/motifs and their sometimes blurred lines of function.

  17. Rh immunoglobulin utlization after spontaneous and induced abortion.

    PubMed

    Grimes, D A; Ross, W C; Hatcher, R A

    1977-09-01

    To monitor the utilization of Rh immunoglobulin (RhIG), we reviewed the charts of 389 spontaneous and 1350 induced abortion patients treated in 1975 at a metropolitan hospital. The rate of ascertainment of Rh type was significantly higher for induced (99.6%) than for spontaneous abortion patients (95.1%) (P less than 0.001). Utilization of Rh immunoglobulin (RhIG) also was significantly higher for induced (98.9%) than for spontaneous abortion patients (80.6%) (P less than 0.001). Women at risk who did not receive RhIG after spontaneous abortion were mostly young, of low gravidity, and at gestational ages (mean 14.4 weeks) associated with substantial risks of Rh sensitization. Eradication of Rh hemolytic disease requires improvement in the system of identifying and treating patients who need prophylaxis.

  18. Serum immunoglobulins and complement (C'3) in oral lichen planus.

    PubMed

    Sklavounou, A D; Laskaris, G; Angelopoulos, A P

    1983-01-01

    Serum immunoglobulins and complement (C'3) were determined by single radial immunodiffusion according to the method of Mancini and co-workers in fifty patients with oral lichen planus and twenty persons with clinically normal oral mucosa. Significantly increased levels of serum IgG (p less than 0.05) and a significant reduction of serum IgA concentration (p less than 0.05) in the experimental group as compared with normal controls were observed. Mean serum IgM and complement (C'3) levels were similar in patients and controls. No correlation between disease variety or extensiveness and immunoglobulin or complement levels was noticed. These results suggest that patients with oral lichen planus may have a generalized immunologic disorder in which humoral immunity is disturbed. Whether humoral immunity is of etiologic significance, contributes to the disease process, or, finally, represents an event secondary to the pathologic changes seen in the disease remains to be determined.

  19. [Optimization of gel radial diffusion method for serum immunoglobulin analysis].

    PubMed

    Gerasimov, I G; Zorkova, E V

    2002-07-01

    Serum IgA, IgM, and IgG were measured by radial immunodiffusion in gel; immunoglobulin concentrations correlated with the diameter of their diffusion. A theoretically-based equation was derived; use of this equation will help estimate serum Ig content without plotting a calibration curve by the square diameter of the immunodiffusion ring of undiluted reference serum in a wide range of concentrations (0.3-3 mg/ml for IgA and IgM and 2-18 mg/ml for IgG). This modification of measuring serum immunoglobulins by radial immunodiffusion in gel is as accurate as other methods, but is reagent- and time-saving.

  20. Immunoglobulin concentrations in human tears in ocular diseases.

    PubMed Central

    Sen, D K; Sarin, G S

    1979-01-01

    Immunoglobulin concentrations in human tears were determined in 165 patients with different eye diseases by a standard radial immunodiffusion method. IgA was present in all the samples in measurable quantity. The mean IgA values were significantly higher than the controls in patients with acute bacterial conjunctivitis, keratomalacia, corneal graft reaction, blepharoconjunctivitis, and acute keratoconjunctivitis. The values in the patients with vernal conjunctivitis, phlyctenular conjunctivitis, acute bacterial corneal ulcer, and acute endogenous uveitis were not significantly different from those in the controls. IgG could be detected in the majority of the samples but it was in measurable quantity in 18 samples. IgM could be detected in fewer samples. IgD was not detected in any of them. The study indicates that, whenever the immunoglobulin levels in tears are altered in diseased eyes, it is the IgA level that is predominantly altered and not the IgG level. PMID:465402

  1. 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.

  2. 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.

  3. Altered secretory immunoglobulin A on skin surface after intensive exercise.

    PubMed

    Eda, Nobuhiko; Shimizu, Kazuhiro; Suzuki, Satomi; Tanabe, Yoko; Lee, Eunjae; Akama, Takao

    2013-09-01

    The aim of this study was to determine the effects of high-intensity endurance exercise on skin immunity by estimating secretory immunoglobulin A (SIgA) and staphylococci on skin surface. Seven healthy adult men (age, 22.3 ± 2.0 years) performed bicycle exercise at 75% HRmax for 60 minutes from 2030 to 2130 hours. Secretory immunoglobulin A was obtained from 1 ml extraction liquids stirred with the microtube homogenizer in the open end of a polypropylene tube for 60 seconds. Secretory immunoglobulin A concentrations were measured using enzyme-linked immunosorbent assay. Staphylococci were harvested by pressed agar-based media against skin surface. Skin surface samples were collected from the chest and the forearm on the first day at 2030 hours (before rest, A1), 2130 hours (after rest, A2), and 2230 hours (after showering, A3); the next morning at 0700 hours (A4); on the second day at 2030 hours (before exercise, B1), 2130 hours (after exercise, B2), and 2230 hours (after showering, B3); and the next morning at 0700 hours (B4). Secretory immunoglobulin A concentration on the forearm was significantly lower at B2 (p < 0.05) and B3 (p < 0.05) than that at B1 and that on the chest at B1 tended to be higher compared with B2 (p = 0.084) and B3 (p = 0.075). The number of staphylococci was significantly higher at B2 than that at B1 (p < 0.01) and B4 (p < 0.01) on the forearm. We conclude that high-intensity endurance exercise might depress immune function and enhance infectious risk on skin surface. Coaches should encourage their athletes to take a shower and change into clean clothes immediately after sports activities and athletes should maintain a clean skin surface to decrease the infectious risk on skin surface.

  4. 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

  5. Endogenous immunoglobulins and sepsis: New perspectives for guiding replacement therapies.

    PubMed

    Bermejo-Martin, Jesús F; Giamarellos-Bourboulis, Evangelos J

    2015-12-01

    The recently emerging concept of immunosuppression developing in the field of severe sepsis generated the need to measure circulating immunoglobulins as part of the necessary tests to evaluate immunocompetence status in patients suffering from this condition. Serum concentrations can be used as a surrogate marker of the final outcome and as a biomarker to explore the need for supplementation of the host with intravenous immunoglobulin preparations. Available evidence from recent clinical studies pinpoints the main observations. The first is that circulating IgM is a phenomenon associated with progression from severe sepsis to septic shock. Deficient kinetics of circulating IgM during the first 7 days following the start of vasopressors is linked with unfavourable outcome. The second is the development of immunoscores using low levels of IgM, IgG1 and IgA. These immunoscores can predict 28-day mortality with an odds ratio ranging between 3 and 5. Novel techniques for evaluating patient's immune status are shedding new light on the development of modern therapeutics where immunoglobulin replacement may be part of a personalised therapeutic approach.

  6. Immunoglobulin Cmu RNA in T lymphoma cells is not translated.

    PubMed

    Walker, I D; Harris, A W

    1980-11-20

    It is widely believed that immunoglobulin genes might encode at least part of the receptor for antigen on the T lymphocyte. Evidence supporting this comes from the effects of anti-immunoglobulin idiotype antibodies on cellular immune networks and from the presence of idiotypes on immunologically active factors from T cells. Detailed molecular characterization of the receptors, however, has been seriously hampered by the lack of a suitable cellular source from which it might be isolated. The recent demonstration of Kemp et al. that thymocytes and certain cultured lines of mouse T lymphoma cells contain polyadenylated RNA molecules encoded by the immunoglobulin Cmu gene (Cmu RNA) prompted us to identify the corresponding protein molecules in those cells. As the haploid mouse genome contains a single Cmu gene, any polypeptide encoded by this gene should react with at least some of the antibodies present in rabbit anti-mouse IgM antiserum. In this letter we report that a number of T lymphoma lines, regardless of whether they contain Cmu RNA, synthesize no detectable mu polypeptides.

  7. Small quantities of erythrocyte bound immunoglobulins and autoimmune haemolysis.

    PubMed Central

    Sokol, R J; Hewitt, S; Booker, D J; Stamps, R

    1987-01-01

    Enzyme linked and radioimmune direct antiglobulin tests (DAGTs) were used to assess red cell bound IgG, IgA, and IgM in 585 patients referred to an immunohaematology reference centre. One hundred and fifty eight patients with less than or equal to 200 mol IgG and small amounts of IgA and IgM coating their red cells were studied in detail. The presence of autoimmune haemolysis was determined from the clinical, haematological, and biochemical findings; it occurred in at least 25% of the 158 patients, the degree varying widely. There was a highly significant association between small increases in cell bound immunoglobulins and the presence of autoimmune haemolysis. Immunoglobulins of IgG, IgA, and IgM classes could produce autoimmune haemolysis when the classical agglutination DAGTs were negative; the IgA and IgM were usually found in association with IgG. The haemolytic effect was enhanced by the presence of complement and combinations of immunoglobulin classes on the red cells. PMID:3558858

  8. Phylogeny of immunoglobulin structure and function. VII. Monomeric and tetrameric immunoglobulins of the margate, a marine teleost fish.

    PubMed Central

    Clem, L W; McLean, W E

    1975-01-01

    The margate, a marine teleost fish, was found to contain both high (16S) and low (7S) molecular weight antibodies 17 days after initial immunization. The 16S antibodies were detectable with both haemagglutination and antigen-binding assays, whereas the 7S antibodies were only detected by the latter technique. Margate 16S (molecular weight approximately 700,000) and 7S (molecular weight approximately 175,000) immunoglobulins were isolated and shown to be antigenically indistinguishable. They therefore appear to belong to the same immunoglobulin class and to have a tetramer--monomer relationship. Experiments with stored sera indicated the 7S protein is probably not an in vitro degradation product of the 16S molecule. Images FIG. 3 FIG. 4 PMID:1184121

  9. Evaluation of the transfer of immunoglobulin from colostrum anaerobic fermentation (colostrum silage) to newborn calves.

    PubMed

    Saalfeld, Mara H; Pereira, Daniela I B; Borchardt, Jessica L; Sturbelle, Regis T; Rosa, Matheus C; Guedes, Marcio C; Gularte, Marcia A; Leite, Fábio P Leivas

    2014-11-01

    Colostrum silage is an anaerobic fermentation methodology of excess farm colostrum used to conserve and provide as milk replacement for calves. The present study aimed to evaluate the levels of immunoglobulins present in bovine colostrum silage and its absorption by newborn calves. The concentration of immunoglobulins was determined in fresh colostrum and colostrum silage stored for 12 months. The absorption of immunoglobulins by calves was assessed immediately after birth and 24 h after colostrum silage intake. The immunoglobulin levels were evaluated by ELISA. The results highlighted that colostrum silage kept similar levels of immunoglobulins as the ones in colostrum in natura, and can be transferred to newborn calves with similar amounts to calves fed with colostrum in natura. It is concluded that colostrum silage keeps viable immunoglobulins, and is able to transfer passive immunity to newborn calves.

  10. 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…

  11. 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

  12. 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

  13. 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.

  14. Reactions of immunoglobulin G-binding ligands with platelets and platelet-associated immunoglobulin G.

    PubMed Central

    Rosse, W F; Devine, D V; Ware, R

    1984-01-01

    Immunoglobulin G (IgG) bound to platelets is usually detected by one of two general methods: binding of labeled anti-IgG or consumption of anti-IgG. The latter method gives, in general, values 5-10-fold greater than the former under the same conditions. To investigate these discrepancies, we have compared the detection of platelet-bound IgG by a labeled anti-IgG binding assay and by a quantitative antiglobulin consumption test using the same antibodies. The interaction of 125I-labeled monoclonal anti-IgG or polyclonal anti-IgG with washed and IgG-coated platelets was studied. The binding of these ligands to washed normal platelets was largely (50-80%) nonspecific; the binding was not saturable and was only partially inhibitable by excess unlabeled anti-IgG. The binding of anti-IgG to platelets coated with anti-PIA1, a platelet-specific IgG antibody, appeared to be saturable and inhibitable; the dissociation constant (KD) of this IgG-anti-IgG reaction was 4.9 X 10(-9) for monoclonal and 1.4 X 10(-7) for polyclonal anti-IgG. The ratio of sites present on the membrane (determined by 131I-labeled anti-PIA1) to the number of binding sites for anti-IgG determined by Scatchard analysis was 0.53 for monoclonal anti-IgG and 1.3 for polyclonal anti-IgG. The binding of monoclonal anti-IgG to platelet-bound immune complexes or IgG aggregates appeared to be complex. 131I-Labeled IgG was affixed to platelets and was detected by three tests: direct binding of radiolabeled monoclonal anti-IgG and quantitative antiglobulin consumption (QAC) tests, which were quantitated either by measuring directly the amount of radiolabeled anti-IgG consumed from fluid phase (direct QAC), or indirectly by reference to a calibration curve relating the consumption of anti-IgG by known amounts of fluid-phase, non-immune IgG (indirect QAC). The amount of platelet-bound IgG detected by the direct binding of 125I-labeled monoclonal anti-IgG and by the direct QAC approximated that known to be bound to

  15. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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)....

  16. 21 CFR 866.5520 - Immunoglobulin G (Fab fragment specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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)....

  17. 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)....

  18. Managing patients with side effects and adverse events to immunoglobulin therapy.

    PubMed

    Azizi, Gholamreza; Abolhassani, Hassan; Asgardoon, Mohammad Hossein; Shaghaghi, Shiva; Negahdari, Babak; Mohammadi, Javad; Rezaei, Nima; Aghamohammadi, Asghar

    2016-01-01

    Immunoglobulin therapy has not only served as a lifesaving approach for the prevention and treatment of infections in primary and secondary immunodeficiency diseases, but has also been used as an immunomodulatory agent for autoimmune and inflammatory disorders and to provide passive immunity for some infectious diseases. Most of the adverse effects associated with immunoglobulin therapy are mild, transient and self-limiting. However, serious side effects also occur. Therefore, to minimize the adverse events of immunoglobulin therapy, specialist review of patient clinical status and immunoglobulin products, in addition to selection of appropriate treatment strategy for the management of patients with associated side effects and adverse events, are crucial.

  19. 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.

  20. 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...

  1. 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...

  2. 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.

  3. Intravenous immunoglobulin transfusion in colostrum-deprived dairy calves.

    PubMed

    Boccardo, A; Belloli, A; Biffani, S; Locatelli, V; Dall'Ara, P; Filipe, J; Restelli, I; Proverbio, D; Pravettoni, D

    2016-03-01

    Immunoglobulin transfusion is employed in the management of the failure of passive transfer (FPT). The aim of this study was to investigate the dose of immunoglobulin G (IgG) needed to reach a protective concentration (>10 g/L) in colostrum-deprived dairy calves. Twenty-eight Holstein Friesian newborn male calves were randomly assigned to either a control group (CG) or a treatment group (PG). Calves in the CG received 4 L of high quality colostrum within 12 h of birth. Calves in the PG received 62.7 ± 3.1 g of IgG IV in 2.6 ± 0.3 L of plasma within 6 h after birth. Serum immunoglobulin G (sIgG) and serum total protein (sTP) concentrations were assayed before and after (24 h, 72 h and 1 week after birth) plasma transfusion or colostrum ingestion. Serum (s) IgG and sTP concentrations increased in both groups throughout the period of observation. Mean sIgG and sTP concentrations after colostrum ingestion or plasma transfusion were higher in the CG than in the PG (P <0.01). Nine treated calves developed diarrhoea during the study and four were humanely euthanased due to progressive clinical deterioration. None of the calves in the CG showed signs of disease or died during the study. The dose of IgG used in this trial effectively provided an adequate sIgG concentration in colostrum-deprived calves (>10 g/L). Calves in the CG had significantly lower morbidity and mortality rates compared to those in the PG, suggesting that plasma transfusion alone is ineffective in providing complete protection against neonatal disease.

  4. Immunomodulatory activity accompanying chicken egg yolk immunoglobulin Y.

    PubMed

    Polanowski, A; Zabłocka, A; Sosnowska, A; Janusz, M; Trziszka, T

    2012-12-01

    Immunity transfer from a mother to the newborn does not depend exclusively on immunoglobulins. Peptides, which are characterized by immunoregulatory properties that accompany IgG(2), known as proline-rich polypeptide complex (PRP), have been discovered for the first time in ovine colostrum. In this report we present new data showing that some immunoregulatory peptides associated with the main immunoglobulin class, IgY, are also present in the avian immune system. Cytokine-inducing activity of particular fractions obtained from ovine colostrum, IgG+ (IgG(2) containing PRP), IgG- (IgG(2) free of PRP), and purified PRP, was compared with that of crude egg yolk IgY (IgY+), additionally purified egg yolk IgY (IgY-), and polypeptides accompanying IgY named Yolkin (Y), using an ex vivo model of whole human blood cells. It was shown that both IgG+ fraction and PRP, but not IgG-, stimulated the whole blood cells to release tumor necrosis factor-α and interleukin-1β cytokines. Similar experiments performed with hen's egg IgY preparations showed that IgY+ and Y samples showed higher cytokine-inducing activity than samples additionally purified with the use of size exclusion chromatography (IgY-). The IgY+ at a dose of 100 μg was even more active than the positive lipopolysaccharide control. It was also found that Y is able to stimulate macrophage cell line J774.2 to release nitric oxide. The results obtained suggest that IgY, the main chicken immunoglobulin fraction, is accompanied by additional polypeptides and plays a role of a transporter of biologically active substances, which was observed in the case of colostral IgG.

  5. 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

    2014-09-07

    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.

  6. 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.

  7. 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

  8. Clonal immunoglobulin gene rearrangement in the infarcted lymph node syndrome.

    PubMed

    Laszewski, M J; Belding, P J; Feddersen, R M; Lutz, C T; Goeken, J A; Kemp, J D; Dick, F R

    1991-07-01

    The authors report a case of complete lymph node infarction in which a specific etiology could not be determined by morphologic or immunophenotypic studies; however, clonal rearrangement of the immunoglobulin gene was demonstrated by Southern blot hybridization of DNA extracted from the necrotic tissue. A subsequent lymph node biopsy later was diagnosed as malignant lymphoma, using morphologic, immunophenotypic and genotypic criteria. Identical clonally rearranged bands were present in DNA from both the infarcted nodal and the subsequent tissue biopsies. In the setting of lymph node necrosis, gene rearrangement studies may provide diagnostic information concerning clonality, even if morphologic and immunophenotypic studies are indeterminate for a lymphoproliferative process.

  9. 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

  10. 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

  11. Tuberculosis in a case of hyper immunoglobulin E syndrome

    PubMed Central

    Ashtekar, Renuka; Shah, Ira

    2016-01-01

    Hyper immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder characterized by elevated serum IgE, dermatitis, and immunodeficiency that predisposes to multiple skin and lung infections. The most frequent pathogen responsible for infections in these patients is Staphylococcus aureus. Tuberculosis (TB) in patients with HIES is an uncommon finding, and there are only a few reports of mycobacterial infections in known cases of HIES. We present a case of abdominal TB that developed in a 15-year-old boy who also had HIES.

  12. Production and characterization of monoclonal antibodies against dog immunoglobulin isotypes.

    PubMed

    Arce, C; Moreno, A; Millán, Y; Martín de las Mulas, J; Llanes, D

    2002-09-06

    A panel of six monoclonal antibodies (mAbs) recognizing antigenic determinants on canine immunoglobulin (Ig) heavy or light chains was produced and characterized. All monoclonals recognized the IgG(2) subclass, although only two were subclass-specific (CA3H1 and CA4F1). The CA3B8 mAb was found to be specific for an epitope on canine immunoglobulin G heavy chain, (IgG(1) and IgG(2) subclasses). Two mAbs (CA2E9 and CA5B2) reacted with an epitope on the heavy chain of canine IgG and IgM and another, CA4E7, bound to canine IgA, IgG and IgM isotypes; CA4E7 recognized an epitope on canine immunoglobulin light chain. CA4E7, CA4F1 and CA5B2 recognized an epitope in the Fab region. Three mAbs, CA3B8, CA4E7 and CA5B2, showed much lower reactivity with canine IgG by ELISA when IgG was periodate-treated, suggesting that they recognized a carbohydrate determinant. Cross-reactivity analysis of these mAbs with sera from horse, goat, cow, sheep, pig, cat, rabbit, hamster, rat, mouse and human indicated that two mAbs, CA3B8 and CA5B2, recognized a canine IgG-specific epitope; two others, CA3H1 and CA4E7, recognized an epitope also present in rabbit and sheep immunoglobulin respectively; and the remaining two (CA2E9 and CA4F1) recognized an epitope broadly present on the Igs of the species analyzed. This panel of antibodies will be a useful tool for future canine immunodiagnosis tests. With the exception of CA2E9, all mAbs were able to recognize plasma cells on paraffin-embedded tissues, and will thus be useful for immunohistochemical assays.

  13. [Exfoliative dermatitis as a side effect of intravenous immunoglobulin treatment].

    PubMed

    Markvardsen, Lars Høj; Jakobsen, Johannes

    2011-10-24

    Three patients with immune-mediated polyneuropathies developed rash, eczema, whole body scaling, vesicles in hands and loss of hair a few days after infusion of large doses of intravenous immunoglobulin (IVIG). The condition was diagnosed as exfoliative dermatitis. Two out of three patients were afterwards treated with low doses of IVIG slowly increased over a year given under the protection of oral steroids. Our findings indicate that exfoliative dermatitis can be provoked by IVIG treatment, and that the treatment can be reinstalled by slowly increasing the IVIG dose under steroid cover.

  14. Evidence for gene conversion among immunoglobulin heavy chain variable region genes.

    PubMed

    Clarke, S H; Rudikoff, S

    1984-03-01

    We have previously reported that the VH region amino acid sequence of a phosphocholine (PC)-binding hybridoma antibody of CBA/J origin, HP101 6G6 (6G6), differs extensively from the VH regions of other PC-binding antibodies. The sequence of 6G6 VH appears to be derived from a gene homologous to the BALB/c V11 gene, a member of the PC VH (T15 VH) gene family not normally used to encode PC-binding antibodies. The 6G6 VH sequence differs from the translated sequence of V11 by six amino acids, four of which occur at the same position in other members of this gene family. This coincidence led to the proposal that the 6G6 VH gene was derived by gene conversion involving three genes of the PC VH gene family. We report here the nucleic acid sequence of the rearranged VH gene of hybridoma 6G6. This sequence supports our previous suggestion of gene conversion by confirming those differences, relative to the BALB/c V11 gene sequence, that are encoded by other members of this gene family, and extends this correlation to include three silent base pair substitutions as well. In addition, 5' noncoding region sequence and Southern blot analysis using probes derived from the coding and 5' noncoding regions confirm that the 6G6 VH gene is likely to be derived from the V11 homologue in CBA/J mice, and suggest that all three genes believed to be involved in the generation of the 6G6 VH gene are present in the CBA/J genome, a prerequisite for their involvement in gene conversion.

  15. Functional Versatility of AGY Serine Codons in Immunoglobulin Variable Region Genes

    PubMed Central

    Detanico, Thiago; Phillips, Matthew; Wysocki, Lawrence J.

    2016-01-01

    In systemic autoimmunity, autoantibodies directed against nuclear antigens (Ags) often arise by somatic hypermutation (SHM) that converts AGT and AGC (AGY) Ser codons into Arg codons. This can occur by three different single-base changes. Curiously, AGY Ser codons are far more abundant in complementarity-determining regions (CDRs) of IgV-region genes than expected for random codon use or from species-specific codon frequency data. CDR AGY codons are also more abundant than TCN Ser codons. We show that these trends hold even in cartilaginous fishes. Because AGC is a preferred target for SHM by activation-induced cytidine deaminase, we asked whether the AGY abundance was solely due to a selection pressure to conserve high mutability in CDRs regardless of codon context but found that this was not the case. Instead, AGY triplets were selectively enriched in the Ser codon reading frame. Motivated by reports implicating a functional role for poly/autoreactive specificities in antiviral antibodies, we also analyzed mutations at AGY in antibodies directed against a number of different viruses and found that mutations producing Arg codons in antiviral antibodies were indeed frequent. Unexpectedly, however, we also found that AGY codons mutated often to encode nearly all of the amino acids that are reported to provide the most frequent contacts with Ag. In many cases, mutations producing codons for these alternative amino acids in antiviral antibodies were more frequent than those producing Arg codons. Mutations producing each of these key amino acids required only single-base changes in AGY. AGY is the only codon group in which two-thirds of random mutations generate codons for these key residues. Finally, by directly analyzing X-ray structures of immune complexes from the RCSB protein database, we found that Ag-contact residues generated via SHM occurred more often at AGY than at any other codon group. Thus, preservation of AGY codons in antibody genes appears to have been driven by their exceptional functional versatility, despite potential autoreactive consequences. PMID:27920779

  16. Clues to pathogenesis of Waldenström macroglobulinemia and immunoglobulin M monoclonal gammopathy of undetermined significance provided by analysis of immunoglobulin heavy chain gene rearrangement and clustering of B-cell receptors.

    PubMed

    Varettoni, Marzia; Zibellini, Silvia; Capello, Daniela; Arcaini, Luca; Rossi, Davide; Pascutto, Cristiana; Rattotti, Sara; Mangiacavalli, Silvia; Pochintesta, Lara; Gotti, Manuel; Gaidano, Gianluca; Cazzola, Mario

    2013-11-01

    We characterized immunoglobulin heavy chain (IGH) gene rearrangements and searched for clusters of stereotyped B-cell receptors in 123 patients with Waldenström macroglobulinemia (WM; n = 59) or immunoglobulin M monoclonal gammopathy of undetermined significance (IgM-MGUS) (n = 64). A productive monoclonal IGHV-D-J rearrangement was obtained in 99/123 patients (80%). Immunoglobulin heavy chain variable (IGHV) genes were mutated in 94/99 patients (95%) with a median somatic hypermutation rate of 6.7% (2.1-14.5). Compared with the normal B-cell repertoire, patients with WM/IgM-MGUS showed an over-representation of the IGHV3 subgroup (83% vs. 55%, p < 0.0001) and an under-representation of IGHV1 (7% vs. 14%, p = 0.04) and IGHV4 (7% vs. 23%, p = 0.0001) subgroups. At the gene level, in WM/IgM-MGUS there was an over-representation of IGHV3-23 (24% vs. 12%, p = 0.0003), IGHV3-64 (3% vs. < 1%, p = 0.003), IGHV3-7 (12% vs. 4%, p = 0.0001) and IGHV3-74 (9% vs. 2%, p < 0.0001), while IGHV4-39 was never used (0 vs. 5%, p = 0.03). Intra-WM/IgM-MGUS search for HCDR3 similarity showed no association fulfilling criteria for stereotyped receptors. WM/IgM-MGUS sequences were unrelated to known chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL) or mantle cell lymphoma (MCL) subsets. In conclusion, the IGHV gene usage in WM and IgM-MGUS is remarkably biased as compared to the normal B-cell repertoire. WM and IgM-MGUS-specific HCDR3 clusters do not occur with a frequency detectable with currently available databases, not supporting a B-cell receptor-driven pathogenesis in WM and IgM-MGUS.

  17. Streptococcus pneumoniae antibody titres in patients with primary antibody deficiency receiving intravenous immunoglobulin (IVIG) compared to subcutaneous immunoglobulin (SCIG).

    PubMed

    Knutsen, A P; Leiva, L E; Caruthers, C; Rodrigues, J; Sorensen, R U

    2015-10-01

    Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are effective in the treatment of patients with primary antibody deficiency disorders (PAD). The purpose of this study was to evaluate Streptococcus pneumoniae (Spn) antibody titres to 14 serotypes in patients receiving IVIG compared to SCIG and to correlate Spn antibody levels to clinical outcome. The doses of immunoglobulin (Ig)G/kg/month were similar in both IVIG and SCIG groups. In 11 patients treated with IVIG, Spn antibody titres were ≥ 1·3 μg/ml to 99·4 ± 2·1% of the 14 serotypes at peak IVIG but decreased to 66·9 ± 19·8% at trough IVIG. Loss of Spn titres ≥ 1·3 μg/ml was most frequent for Spn serotypes 1, 4, 9V and 23. This correlated with lower Spn antibody titres to these serotypes at peak IVIG compared to the other serotypes. In 13 patients treated with SCIG, Spn antibody titres were protective to 58·2 ± 23·3% of the serotypes 3-5 days after infusion, similar to trough IVIG. Similarly, the Spn serotypes with the least protective percentages were the same as the ones observed in trough IVIG. There were no annualized serious bacterial infections (aSBI) in either group. However, there were significantly decreased annualized other infections (aOI) in the SCIG group compared to the IVIG-treated group, 0·8 ± 0·7 versus 2·2 ± 1·2 infections/patient/year (P = 0·004). Breakthrough aOI did not correlate with protective or higher serum Spn antibody titres.

  18. 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.

  19. 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.

  20. 7th International Immunoglobulin Conference: Mechanisms of action.

    PubMed

    Basta, M; Branch, D R

    2014-12-01

    Although intravenous immunoglobulin (IVIg) is widely used for replacement therapy in immunodeficiencies and to treat autoimmune and inflammatory diseases, its mechanisms of action are not fully understood. Examination of immunoglobulin (Ig) receptors, including the Fc-gamma receptors (FCγRs) and the neonatal Fc receptor, have revealed genetic variations that are linked to autoimmune diseases and to the efficacy of IVIg treatment. However, the beneficial effect of IVIg encompasses multiple mechanisms of action. One of these is scavenging of activated complement fragments, such as C3a, C5a, C3b and C4b, by infused Ig molecules. This interaction prevents binding of complement fragments to their receptors on target cells, thus attenuating the immune damage. Additionally, anti-inflammatory effects may be facilitated by IgA via specific receptors and/or complement scavenging. Glycosylation of both the Fc- and Fab-fragments has also been implicated in the anti-inflammatory action of IVIg. Although there is evidence to support a role for sialylated IgG glycovariants in mediating the effect of IVIg, evidence from animal models of inflammatory disease suggest that sialylation may not be a critical factor. However, an increase in IgG glycosylation has been observed following IVIg treatment in Guillain-Barré syndrome patients, and this has been associated with improved clinical outcomes.

  1. Identification of an immunoglobulin Fc receptor of Actinobacillus actinomycetemcomitans.

    PubMed Central

    Mintz, K P; Fives-Taylor, P M

    1994-01-01

    Actinobacillus actinomycetemcomitans expresses proteins that bind to the Fc portion of immunoglobulins. The immunoglobulin Fc receptors on the surface of A. actinomycetemcomitans were detected by the binding of biotinylated human or murine Fc molecules to strain SUNY 465 adsorbed to the bottom of microtiter wells. Biotinylated Fc binding was inhibited by unlabeled Fc molecules and human plasma. Fc receptors were identified by the binding of biotinylated Fc molecules to bacterial membrane proteins separated by polyacrylamide gel electrophoresis and transferred to nitrocellulose. Multiple bands were identified, and the major Fc-binding protein was determined to be a heat-modifiable protein. This protein migrated with approximate molecular weights of 25,000 and 32,000 (unheated and heated, respectively). Amino-terminal sequence analysis of this protein revealed a sequence identical to the heat-modifiable protein described for A. actinomycetemcomitans ATCC 43718. This protein sequence exhibits significant homology with the N termini of outer membrane protein A (OmpA) of Escherichia coli and related OmpA-like proteins from other gram-negative bacteria. Images PMID:7927715

  2. Somatic mutation of immunoglobulin VH6 genes in human infants

    PubMed Central

    Ridings, J; Dinan, L; Williams, R; Roberton, D; Zola, H

    1998-01-01

    Infants respond to antigen by making antibody that is generally of low affinity for antigen. Somatic hypermutation of immunoglobulin genes, and selection of cells expressing mutations with improved affinity for antigen, are the molecular and cellular processes underlying the maturation of antibody affinity. We have reported previously that neonates and infants up to 2 months of age, including individuals undergoing strong immunological challenge, show very few mutated VH6 sequences, with low mutation frequencies in mutated sequences, and little evidence of selection. We have now examined immunoglobulin genes from healthy infants between 2 and 10 months old for mutation and evidence of selection. In this age group, the proportion of VH6 sequences which are mutated and the mutation frequency in mutated sequences increase with age. There is evidence of selection from 6 months old. These results indicate that the process of affinity maturation, which depends on cognate T–B cell interaction and functional germinal centres, is approaching maturity from 6 months old. PMID:9764600

  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. Human immunoglobulin G levels of viruses and associated glioma risk.

    PubMed

    Sjöström, Sara; Hjalmars, Ulf; Juto, Per; Wadell, Göran; Hallmans, Göran; Tjönneland, Anne; Halkjaer, Jytte; Manjer, Jonas; Almquist, Martin; Melin, Beatrice S

    2011-09-01

    Few consistent etiological factors have been identified for primary brain tumors. Inverse associations to asthma and low levels of varicella-zoster virus, immunoglobulin (Ig) levels in prevalent cases have indicted a role for the immune system in the development of glioma. Because samples from prevalent cases of glioma could be influenced by treatments such as steroids and chemotherapy, we investigated pre-diagnostic samples from three large Scandinavian cohorts. To test the hypothesis that immune response levels to these viruses are associated etiologically with glioma risk, we investigated pre-diagnostic immunoglobulin levels for cytomegalovirus (CMV), varicella-zoster virus (VZV), adenovirus (Ad), and Epstein-Barr virus (EBV) including the nuclear antigen (EBNA1) using plasma samples from 197 cases of adult glioma and 394 controls collected from population-based cohorts in Sweden and Denmark. Low VZV IgG levels were marginally significantly more common in glioma cases than the controls (odds ratio (OR) = 0.68, 95% CI 0.41-1.13) for the fourth compared with the first quartile (p = 0.06 for trend). These results were more prominent when analyzing cases with blood sampling at least 2 years before diagnosis (OR = 0.63, 95% CI 0.37-1.08) (p = 0.03). No association with glioma risk was observed for CMV, EBV, and adenovirus.

  5. 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.

  6. [Immunoglobulins in the tear secretion in cases of herpetic keratitis].

    PubMed

    Malachi, A; Stan, C

    1999-01-01

    The goal of this study is to analyse the immunoglobulins of patients with herpetic keratitis. Tears have been collected from 36 patients with herpetic keratitis (study group) and 20 healthy volunteers (control group). Quantitative determination of A, G, M immunoglobulins and secretor IgA has been performed by Mancini radial immunodiffusion method. Our study has revealed the following results: a decrease in IgM and IgA levels compared with control group (p < 0.01) and an increase in secretory IgA compared with fellow eye (p < 0.05) in patients with herpetic keratitis of the first manifestation; eyes with recidivant herpetic keratitis showed higher level of IgA than the control group (p < 0.01) and a higher level of IgG than the first disease manifestation group (p < 0.05); the IgA level in the healthy eye of the patients with herpetic keratitis appeared significantly lower than in the control group (p < 0.001).

  7. Expression of cloned immunoglobulin genes introduced into mouse L cells.

    PubMed Central

    Gilles, S D; Tonegawa, S

    1983-01-01

    Functionally rearranged immunoglobulin heavy-chain (gamma 2b) and light-chain (lambda 1 and kappa) genes were introduced into mouse L tk- cells by co-transformation with the Herpes virus tk gene. Cloned cell lines were selected in HAT medium and tested for the presence of transfected immunoglobulin gene sequences by Southern blotting analysis. It was found that the gamma 2b gene was accurately transcribed at a low level in transfected mouse L cells and cytoplasmic gamma 2b, heavy-chain protein was detected by immunoprecipitation of cell extracts. Light-chain genes, on the other hand, were not accurately transcribed. Instead, lambda 1 or kappa RNA species were detected which were approximately 200 to 300 bases longer than the authentic mRNAs. These results suggest that the expression of rearranged heavy-chain and light-chain genes are controlled differently and that these differences can be seen in transfected, non-lymphoid cells. Images PMID:6316279

  8. Salivary and serum immunoglobulin levels in cats with chronic gingivostomatitis.

    PubMed

    Harley, R; Gruffydd-Jones, T J; Day, M J

    2003-02-01

    The salivary and serum concentrations of immunoglobulins G, M and A (IgG, IgM and IgA), and the salivary concentrations of albumin were measured by ELISA in 30 cats with chronic gingivostomatitis and 32 healthy cats. The cats with chronic gingivostomatitis had significantly higher salivary concentrations of IgG, IgM and albumin, and higher serum concentrations of IgG, IgM and IgA, but significantly lower salivary concentrations of IgA than the healthy cats. The cats with chronic gingivostomatitis were treated with either methylprednisolone, sodium aurothiomalate, metronidazole and spiramycin, or oral hygiene products. After three months of treatment, the cats receiving methylprednisolone had a significant reduction in serum IgG levels compared to the cats treated with sodium aurothiomalate or metronidazole and spiramycin, but after six months of treatment there were no significant differences between the groups. Before the treatments, the levels of oral inflammation were not correlated significantly with any of the serum or salivary immunoglobulin levels. However, the changes in oral inflammation were correlated significantly with the changes in the salivary IgM concentration after three and six months of treatment, and with the change in the salivary IgA concentration after six months of treatment.

  9. Immunoglobulins in the eggs of the nurse shark, Ginglymostoma cirratum.

    PubMed

    Haines, Ashley N; Flajnik, Martin F; Rumfelt, Lynn L; Wourms, John P

    2005-01-01

    Elasmobranchs, which include the sharks, skates, and rays, emerged over 450 million years ago and are the oldest vertebrates to possess an adaptive immune system. They have evolved diverse reproductive modes, with a variety of physiological adaptations that enhance reproductive success. The nurse shark, Ginglymostoma cirratum, is an aplacental, viviparous elasmobranch in which the egg and its associated vitelline vasculature are the primary route for maternal-embryonic interactions. During gestation, nurse shark embryos hatch from their eggcases and develop free in the uterus, which is flushed regularly with seawater. Similar to higher vertebrates, embryonic and neonatal nurse sharks possess an immune system that is not fully competent. In birds and bony fishes, maternal immunoglobulins (Ig) stored in the egg during oogenesis confer protective immunity to embryos during gestation. However, early research suggested that such transfer of passive immunity does not occur in sharks. To better understand how elasmobranch embryos are protected from waterborne pathogens during this potentially vulnerable time, we have re-examined the existence of Igs in elasmobranch eggs. Using monoclonal antibodies, we establish the presence of two classes of Igs in nurse shark eggs: 7S IgM and IgNAR. The potential transfer of immunoglobulins from elasmobranch eggs is discussed.

  10. A Comparative Study of Intravenous Immunoglobulin and Subcutaneous Immunoglobulin in Adult Patients with Primary Immunodeficiency Diseases: A Systematic Review and Meta-Analysis.

    PubMed

    Shabaninejad, Hosein; Asgharzadeh, Asra; Rezaei, Nima; Rezapoor, Aziz

    2016-01-01

    Subcutaneous immunoglobulin (SCIG) is a new therapeutic procedure for patients with primary immunodeficiency (PI). This research is a systematic review of studies on the efficacy and safety of intravenous immunoglobulin (IVIG) and SCIG in adult patients with PI. This study includes a systematic review of cohorts and randomized clinical trials (24 articles) from 5 databases with no time limits. Random effects meta-analysis was performed for outcomes such as efficacy and safety. Standard mean difference (SMD) of serum immunoglobulin level was equal to 0.336 (P <0.01; 0.205-0.467) and the odds ratio (OR) of side effects was 0.497 (P=0.1; 0.180-1.371). The results indicate that SCIG leads to a higher level of immunoglobulin and a reduction in side effects but shows the same infection rate as IVIG. Our analysis shows that shifting from IVIG to SCIG therapy can have clinical benefits for PI patients.

  11. Immunoglobulin M-enriched intravenous polyclonal immunoglobulins reduce bacteremia following Klebsiella pneumoniae infection in an acute respiratory distress syndrome rat model.

    PubMed

    Lachmann, R A; van Kaam, A H L C; Haitsma, J J; Verbrugge, S J C; Delreu, F; Lachmann, B

    2004-06-01

    Mechanical ventilation is known to induce bacterial translocation from the lung into the systemic circulation. This study determined the effect of immunoglobulin M (IgM)-enriched polyclonal immunoglobulins on bacteremia due to ventilation-induced translocation in an acute respiratory distress syndrome (ARDS) rat model with Klebsiella-induced pneumonia. After whole lung lavage, Sprague-Dawley rats intravenously received either a high dose or a low dose of an immunoglobulin preparation, or an albumin solution as control, followed by an intratracheal injection of a Klebsiella pneumoniae solution. Blood colony-forming units (CFUs) in the treatment groups were significantly lower during the 3-hour ventilation period compared to the control group. The authors conclude that IgM-enriched polyclonal immunoglobulins lead to a reduction of bacteria in blood of surfactant-deficient, ventilated rats infected with Klebsiella pneumoniae.

  12. Formation of Amyloid Fibers by Monomeric Light Chain Variable Domains*

    PubMed Central

    Brumshtein, Boris; Esswein, Shannon R.; Landau, Meytal; Ryan, Christopher M.; Whitelegge, Julian P.; Phillips, Martin L.; Cascio, Duilio; Sawaya, Michael R.; Eisenberg, David S.

    2014-01-01

    Systemic light chain amyloidosis is a lethal disease characterized by excess immunoglobulin light chains and light chain fragments composed of variable domains, which aggregate into amyloid fibers. These fibers accumulate and damage organs. Some light chains induce formation of amyloid fibers, whereas others do not, making it unclear what distinguishes amyloid formers from non-formers. One mechanism by which sequence variation may reduce propensity to form amyloid fibers is by shifting the equilibrium toward an amyloid-resistant quaternary structure. Here we identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers. PMID:25138218

  13. 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...

  14. 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....

  15. 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...

  16. 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....

  17. 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...

  18. 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....

  19. 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...

  20. 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....

  1. 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…

  2. 21 CFR 866.5550 - Immunoglobulin (light chain specific) immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... macroglobulinemia (increased production of large immunoglobulins), and connective tissue diseases such as rheumatoid... portions of immunoglobulin molecules in serum, other body fluids, and tissues. In some disease states, an... with gamma globulin molecules, can be found in a patient's body fluids and tissues. Measurement of...

  3. Decreased immunoglobulin E (IgE) binding to cashew allergens following sodium sulfite treatment and heating

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cashew nut and other nut allergies can result in serious and sometimes life threatening reactions. Linear and conformational epitopes within food allergens are important for immunoglobulin E binding. Methods that disrupt allergen structure can reduce immunoglobulin E binding and lessen the likelih...

  4. 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

  5. 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

    2016-02-12

    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.

  6. [Quantitative determination of immunoglobulins in serum and saliva of patients with denture stomatitis].

    PubMed

    Popova, E; Stankova, G; Dermendzieva, S

    1989-01-01

    A quantitative study on the immunoglobulins G, M, and A in serum and saliva was performed as well as of secretory immunoglobulin A and of the secretory component in the saliva of 35 patients with prosthetic stomatitis and 30 healthy controls without prostheses. The method of radial immune-diffusion in agar according to Mancini, modification of G. Stankova et al. (1983) was used. The study established that there was no statistically significant difference (p greater than 0.05) in the values of immunoglobulins G, M and A in the sera of the subjects from both groups. Statistically significant increase (p less than 0.001) of the values of the immunoglobulin A, secretory immunoglobulin A and secretory component was established in the saliva of the patients with prosthetic stomatitis as compared with the same values in the control group, very likely due to the local reaction of saliva to the present prosthetic constructions.

  7. The aberrancy of immunophenotype and immunoglobulin status as indicators of prognosis in B cell diffuse large cell lymphoma.

    PubMed Central

    Spier, C. M.; Grogan, T. M.; Lippman, S. M.; Slymen, D. J.; Rybski, J. A.; Miller, T. P.

    1988-01-01

    To assess the prognostic significance of the immunophenotype in diffuse large cell lymphoma (DLCL), 105 DLCL patients were studied between 1978 and 1987 using a panel of 40 monoclonal antibodies applied to frozen tissue. Eighty-three patients were found to have B cell phenotypes, and 20 patients had T cell phenotypes. Focusing on markers relevant to clinical outcome among B cell LCL showed that lack of expression of the pan B antigens Leu14 and Leu16 were correlated with decreased survival (Leu14, P = 0.01; Leu16, P = 0.06; log-rank). HLA-DR activity also showed that lack of expression of this antigen correlated with poor survival (P = 0.004, log-rank). Kappa light chain immunoglobulin lack of expression showed predictive value for decreased survival as well (P = 0.005, log-rank). Multivariate analyses of known clinically important variables and the immune phenotypes confirm that the loss of HLA-DR and B cell aberrancy are independent factors predicting a poor clinical outcome. Losing some B activation/kappa antigens appears to be a broad biologic phenomenon linking surface antigen lack of expression with decreased survival. This suggests that aberrancy of immunophenotype and immunoglobulin status are key predictors of survival in B-LCL. PMID:3140668

  8. Cell-cell communication mediated by the CAR subgroup of immunoglobulin cell adhesion molecules in health and disease.

    PubMed

    Matthäus, Claudia; Langhorst, Hanna; Schütz, Laura; Jüttner, René; Rathjen, Fritz G

    2016-11-18

    The immunoglobulin superfamily represents a diverse set of cell-cell contact proteins and includes well-studied members such as NCAM1, DSCAM, L1 or the contactins which are strongly expressed in the nervous system. In this review we put our focus on the biological function of a less understood subgroup of Ig-like proteins composed of CAR (coxsackievirus and adenovirus receptor), CLMP (CAR-like membrane protein) and BT-IgSF (brain and testis specific immunoglobulin superfamily). The CAR-related proteins are type I transmembrane proteins containing an N-terminal variable (V-type) and a membrane proximal constant (C2-type) Ig domain in their extracellular region which are implicated in homotypic adhesion. They are highly expressed during embryonic development in a variety of tissues including the nervous system whereby in adult stages the protein level of CAR and CLMP decreases, only BT-IgSF expression increases within age. CAR-related proteins are concentrated at specialized cell-cell communication sites such as gap or tight junctions and are present at the plasma membrane in larger protein complexes. Considerable progress has been made on the molecular structure and interactions of CAR while research on CLMP and BT-IgSF is at an early stage. Studies on mouse mutants revealed biological functions of CAR in the heart and for CLMP in the gastrointestinal and urogenital systems. Furthermore, CAR and BT-IgSF appear to regulate synaptic function in the hippocampus.

  9. 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.

  10. Effects of inorganic or organic selenium on immunoglobulins in swine

    PubMed Central

    2013-01-01

    A study was conducted to determine if Se source fed during gestation and lactation affects passive transfer of immunoglobulins. Sixty days prior to breeding (d -60), gilts were randomly assigned to one of three treatments prior to breeding and throughout gestation: control (Control, no supplemental Se; n = 8), inorganic Se (Inorganic Se, 0.3 ppm; n = 4) and organic Se (Organic Se, 0.3 ppm; n = 4). Blood was collected on d -60, 57 and 113 of gestation and on d 21 of lactation and milk was collected at d 0, 1, 7, 14, and 21 of lactation. Blood was collected from piglets at d 0, 1, 7, 14, and 21 of age. Gilts fed organic Se had greater (P < 0.05) circulating concentrations of Se than Inorganic and Control gilts. Regardless of treatment, circulating concentrations of Se were greatest (P < 0.05) at d -60 compared to all other days. Serum concentrations of IgG were greatest (P < 0.05) in gilts at d 57 of gestation compared to d 113. Serum concentrations of IgA were greatest (P < 0.05) on d 113 of gestation and d 21 of lactation compared to d -60 and 57. Serum concentrations of IgM were greater (P < 0.05) at d 57 compared to d -60. Inorganic gilts had greater (P < 0.05) colostral and milk concentrations of IgG and IgM than Organic or Control gilts. Circulating concentrations of Se in piglets were greatest (P < 0.05) at d 14 and 21 of age compared to all other days. Piglets from gilts supplemented with organic Se had greater (P < 0.05) circulating concentrations of Se on d 1 versus piglets from gilts supplemented with no additional Se. The immunoglobulin concentrations of IgG, IgA, and IgM were lowest (P < 0.05) on d 0 and then increased when compared to d 1. The addition of different sources of Se did not affect the immunoglobulin concentrations in the gilt or piglet. PMID:24280099

  11. Relationships between levels of lysozyme, lactoferrin, salivary peroxidase, and secretory immunoglobulin A in stimulated parotid saliva.

    PubMed Central

    Rudney, J D; Smith, Q T

    1985-01-01

    Recent studies suggest that salivary lysozyme (Lz), lactoferrin (Lf), peroxidase (Spx), and secretory immunoglobulin A (sIgA) may interact in a common antimicrobial system. A multiple protein approach therefore may be needed to determine the role of this system in oral health and ecology. In the present study we investigate the relationships between levels of Lz, Lf, Spx, and sIgA (adjusted for flow rate and total protein) in stimulated parotid saliva from 44 dental students. Principal components analysis was used to determine major patterns of intercorrelation between variables; cluster analysis was used to identify groups of subjects with similar salivary profiles for Lz, Lf, Spx, and sIgA. Spx tended to vary independently of Lz and Lf, which, in turn, tended to vary together. sIgA showed a weak negative relationship with Spx and a weak positive relationship with Lz and Lf. Six major clusters of subjects with similar antimicrobial protein profiles were found. These were significantly different at P less than 0.0001. Spx was the most important determinant of cluster membership followed (in order of importance) by Lz, Lf, and sIgA. Cluster profiles were Spx-, sIgAmu, Lf-, Lz-; Spx-, sIgA+, Lfmu, Lz+; Spxmu, sIgAmu, Lfmu, Lzmu; Spx+, sIgA-, Lf-, Lz-; Spx+, sIgAmu, Lf+, Lz-; and Spx+, sIgAmu, Lf+, Lz+ (-, mu, and + refer to the position of the cluster mean each variable relative to the overall mean for that variable). Results suggest that clusters may be a product of independent variation in the secretory activity of acinar and intercalated duct cells. PMID:4030086

  12. Immunoglobulin A nephropathy. Quantitative immunohistomorphometry of the tonsillar plasma cells evidences an inversion of the immunoglobulin A versus immunoglobulin G secreting cell balance.

    PubMed Central

    Bene, M C; Faure, G; Hurault de Ligny, B; Kessler, M; Duheille, J

    1983-01-01

    Primary IgA nephropathy (Berger's disease) is characterized by renal deposits of IgA, the origin of which is still unknown. However, several clinical and biological findings suggest that these immunoglobulins might have a mucosal origin, and that such patients should present mucosal abnormalities. This paper reports the results of the immunohistomorphometrical analysis of tonsillar plasma cells from seven patients suffering from Berger's disease and seven controls also with recurrent tonsillitis. IgG, IgA, and IgM-secreting cells were enumerated after immunofluorescent staining of serial frozen-cut sections from 20 tonsils. In controls, a predominance of the IgG-secreting population, similar to this reported in the literature was observed (65% of IgG secreting cells and 29% of IgA plasma cells), while an inversion in the patients' plasma cells percentages was evidenced (IgG:37%, IgA:56%). This increment in the IgA population was paralleled by an augmentation of the number of dimeric IgA-secreting cells (75% of IgA plasma cells), stained both for cytoplasmic IgA and J chain. In controls, the latter cells were in similar proportions as previously reported by others (45% of IgA plasma cells). These results demonstrate an imbalance in the IgA-producing system of patients with Berger's disease, which is in keeping with the hypothesis favoring a mucosal origin for the mesangial IgA present in their kidneys. PMID:6406547

  13. 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

  14. 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.

  15. 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.

  16. Sulfasalazine-induced linear immunoglobulin A bullous dermatosis with DRESS.

    PubMed

    Hernández, N; Borrego, L; Soler, E; Hernández, J

    2013-05-01

    Linear immunoglobulin (Ig) A dermatosis is an immune-mediated bullous disease characterized by linear deposits of IgA along the basal membrane. While usually idiopathic, it can occasionally be induced by drug exposure. We report the case of a 60-year-old woman with rheumatoid arthritis being treated with sulfasalazine who developed linear IgA dermatosis and drug rash with eosinophilia and systemic symptoms (DRESS). The dermatosis and associated symptoms resolved following withdrawal of the drug and treatment with systemic corticosteroids for 2 months. This is the first report of sulfasalazine-induced linear IgA dermatosis in association with DRESS and we believe that sulfasalazine should be added to the list of drugs that can cause linear IgA dermatosis.

  17. Direct versus sequential immunoglobulin switch in allergy and antiviral responses.

    PubMed

    Svirshchevskaya, E; Fattakhova, G; Khlgatian, S; Chudakov, D; Kashirina, E; Ryazantsev, D; Kotsareva, O; Zavriev, S

    2016-09-01

    Allergy is characterized by IgE production to innocuous antigens. The question whether the switch to IgE synthesis occurs via direct or sequential pathways is still unresolved. The aim of this work was to analyze the distribution of immunoglobulins (Ig) to house dust mite D. farinae and A. alternata fungus in allergic children with primarily established diagnosis and compare it to Epstein-Barr antiviral (EBV) response in the same patients. In allergy patients the only significant difference was found in allergen specific IgE, likely mediated by a direct isotype switch, while antiviral response was dominated by EBV specific IgG and low level of concordant IgA and IgG4 production consistent with a minor sequential Ig switches. Taken collectively, we concluded that sequential isotype switch is likely to be a much rarer event than a direct one.

  18. 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.

  19. 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

  20. Unusual selective immunoglobulin deficiency in an Arabian foal.

    PubMed

    Boy, M G; Zhang, C; Antczak, D F; Hamir, A N; Whitlock, R H

    1992-01-01

    A 10-month-old Arabian foal was evaluated for a suspected immunoglobulin (Ig) M deficiency. Decreased to nondetectable concentrations of IgM, IgA, and IgG (T), and a normal concentration of IgG, were present. Results of in vitro testing of the blood lymphocyte blastogenesis showed a weak response to the B-cell mitogen, lipopolysaccharide (LPS), but normal responses to T-cell mitogens. Results of postmortem examination showed synovitis of the left tibiotarsal and both scapulohumeral joints. Atrophy and edema of the lymph nodes and lymphocyte depletion in the thymus and spleen were seen. A subacute inflammatory infiltrate was observed in the kidney, synovium, liver, and brain. Etiologic agents were not identified. This case represents a previously unreported form of immunodeficiency disease in the horse.

  1. [Sialochemistry in nonneoplastic diseases of parotid gland: immunoglobulins and electrolytes].

    PubMed

    Wang, S; Zhu, X; Zhu, J

    1996-07-01

    The concentration and total value of immunoglobulins (SIgA, IgG) and electrolytes (sodium, potassium, chlorine, calcium and phosphorus) in mixed saliva were examined in 28 patients with Sjögren's syndrome (SS), 25 with chronic obstructive parotitis (COP), 32 with sialadenosis and 32 normal controls. The results showed that in SS group, total saliva flow rate was decreased: concentration of SIgA, IgG, electrolytes was significantly elevated; but total value of SIgA, IgG, electrolytes was markedly decreased. Decreased total value of sodium, potassium, chlorine and calcium was revealed in COP group. Elevated concentration and total value of phosphorus was found in sialadenosis group. This study indicates that examination of total value of immunoglobins and electrolytes has greater value than that of concentration. The possible mechanism of changes observed is discussed.

  2. 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

  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. Immunoglobulin M for Acute Infection: True or False?

    PubMed Central

    2016-01-01

    Immunoglobulin M (IgM) tests have clear clinical utility but also suffer disproportionately from false-positive results, which in turn can lead to misdiagnoses, inappropriate therapy, and premature closure of a diagnostic workup. Despite numerous reports in the literature, many clinicians and laboratorians remain unaware of this issue. In this brief review, a series of virology case examples is presented. However, a false-positive IgM can occur with any pathogen. Thus, when an accurate diagnosis is essential for therapy, prognosis, infection control, or public health, when the patient is sick enough to be hospitalized, or when the clinical or epidemiologic findings do not fit, IgM detection should not be accepted as a stand-alone test. Rather, whenever possible, the diagnosis should be confirmed by other means, including testing of serial samples and the application of additional test methods. PMID:27193039

  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. 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.

  7. Ubiquitination Events That Regulate Recombination of Immunoglobulin Loci Gene Segments

    PubMed Central

    Chao, Jaime; Rothschild, Gerson; Basu, Uttiya

    2014-01-01

    Programed DNA mutagenesis events in the immunoglobulin (Ig) loci of developing B cells utilize the common and conserved mechanism of protein ubiquitination for subsequent proteasomal degradation to generate the required antigen-receptor diversity. Recombinase proteins RAG1 and RAG2, necessary for V(D)J recombination, and activation-induced cytidine deaminase, an essential mutator protein for catalyzing class switch recombination and somatic hypermutation, are regulated by various ubiquitination events that affect protein stability and activity. Programed DNA breaks in the Ig loci can be identified by various components of DNA repair pathways, also regulated by protein ubiquitination. Errors in the ubiquitination pathways for any of the DNA double-strand break repair proteins can lead to inefficient recombination and repair events, resulting in a compromised adaptive immune system or development of cancer. PMID:24653725

  8. [Hyper-immunoglobulin E syndrome: report of one case].

    PubMed

    Aguilera, Guillermo; Cárcamo, Guillermo; Sepúlveda, Juan; Vinet, Ana María; Martínez, Carlos

    2015-06-01

    The Hyperimmunoglobulin E syndrome (HIES) is a rare sporadic or autosomal dominant immune and connective tissue disorder characterized by chronic eczema, cutaneous abscesses, pneumonias, invasive infections, high levels of Immunoglobulin E, primary teeth retention and bone abnormalities. We report a 24-year-old male with a history of cutaneous abscesses and esophageal candidiasis. He was admitted due to a left gluteal cellulitis. During the fifth day of hospitalization he presented a distal necrosis of the fourth finger of the right hand. Laboratory results showed high levels of IgE and positive cryoglobulins. The patient was discharged and was admitted again five days later with a new gluteal abscess. IgE levels were even higher. Applying Grimbacher scale, the diagnosis of Hyperimmunoglobulin E syndrome was reached.

  9. Immunoglobulin octanucleotide: independent activity and selective interaction with enhancers

    SciTech Connect

    Parslow, T.G.; Jones, S.D.; Bond, B.; Yamamoto, K.R.

    1987-03-20

    The thymidine kinase (tk) promoter of herpes simplex virus includes an octanucleotide sequence motif (ATTTGCAT) that is also an essential component of immunoglobulin kappa gene promoters. In the absence of an enhancer, tk promoter derivatives that contain this element support a higher rate of transcription than those that lack it. The action of the kappa enhancer augments that of the octanucleotide in B lymphoid cells; when both elements are present, tk promoter activity is increased by more than an order of magnitude. In contrast, the presence of the octanucleotide in this promoter markedly reduces its response to a nonimmunoglobulin enhancer. These results suggest that the octanucleotide may mediate a selective interaction among promoters and enhancers.

  10. Autoimmunity in Common Variable Immunodeficiency

    PubMed Central

    Agarwal, Shradha; Cunningham-Rundles, Charlotte

    2010-01-01

    Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. Although the hallmark of CVID is hypogammaglobulinemia, the intrinsic dysregulation of the immune system leads to defective T-cell activation and proliferation, as well as dendritic cell and cytokine defects. Although 70% to 80% of patients have had recurrent sinopulmonary infections, auto-immunity and inflammatory complications are also common. The most common autoimmune conditions are immune thrombocytopenic purpura and hemolytic anemia, but other autoimmune complications arise, including rheumatoid arthritis, pernicious anemia, primary biliary cirrhosis, thyroiditis, sicca syndrome, systemic lupus, and inflammatory bowel disease. Treatment of autoimmunity includes high-dose immunoglobulins, corticosteroids, selected immunosuppressants, and other immune modulators. This review focuses on autoimmune conditions associated with CVID, potential mechanisms of immune dysregulation, and therapeutic strategies. PMID:19671377

  11. Enhancer Complexes Located Downstream of Both Human Immunoglobulin Cα Genes

    PubMed Central

    Mills, Frederick C.; Harindranath, Nagaradona; Mitchell, Mary; Max, Edward E.

    1997-01-01

    To investigate regulation of human immunoglobulin heavy chain expression, we have cloned DNA downstream from the two human Cα genes, corresponding to the position in the mouse IgH cluster of a locus control region (LCR) that includes an enhancer which regulates isotype switching. Within 25 kb downstream of both the human immunoglobulin Cα1 and Cα2 genes we identified several segments of DNA which display B lymphoid–specific DNase I hypersensitivity as well as enhancer activity in transient transfections. The corresponding sequences downstream from each of the two human Cα genes are nearly identical to each other. These enhancers are also homologous to three regions which lie in similar positions downstream from the murine Cα gene and form the murine LCR. The strongest enhancers in both mouse and human have been designated HS12. Within a 135-bp core homology region, the human HS12 enhancers are ∼90% identical to the murine homolog and include several motifs previously demonstrated to be important for function of the murine enhancer; additional segments of high sequence conservation suggest the possibility of previously unrecognized functional motifs. On the other hand, certain functional elements in the murine enhancer, including a B cell–specific activator protein site, do not appear to be conserved in human HS12. The human homologs of the murine enhancers designated HS3 and HS4 show lower overall sequence conservation, but for at least two of the functional motifs in the murine HS4 (a κB site and an octamer motif  ) the human HS4 homologs are exactly conserved. An additional hypersensitivity site between human HS3 and HS12 in each human locus displays no enhancer activity on its own, but includes a region of high sequence conservation with mouse, suggesting the possibility of another novel functional element. PMID:9294139

  12. Immunoglobulin VH and VK genes of the BALB/c anti-foot-and-mouth disease virus (O1) VP1 response: cloning, characterization and transgenic mice.

    PubMed

    Conrad, U; Becker, K; Ziegner, M; Walter, G

    1991-11-01

    Hybridomas producing monoclonal antibodies of different isotypes were isolated from BALB/c antibody responses to the capsid protein VP1 of the foot-and-mouth disease virus (FMDV) strain O1. According to antigen binding measured by ELISA a weak-binding (81D10, IgM) and a strong-binding antibody (113C12, IgG2a) were selected. As RNA sequencing of productive immunoglobulin VH and VK genes turned out, both chains of the weak-binding antibody (81D10) are encoded by germline (i.e. not mutated) genes whereas the gene encoding the strong-binding antibody (113C12) k chain is mutated at several sites. Therefore, rearranged VH and VK genes of 81D10 were cloned, expressed in immunoglobulin non-producing plasmacytoma cells, and mice transgenic for the 81D10 k gene were produced. These mice provide a first step in the development of a transgenic mouse model for genetical investigations in the affinity maturation of anti-viral immunoglobulin variable genes.

  13. 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.

  14. 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.

  15. Factors regulating immunoglobulin production by normal and disease-associated plasma cells.

    PubMed

    Jackson, David A; Elsawa, Sherine F

    2015-01-21

    Immunoglobulins are molecules produced by activated B cells and plasma cells in response to exposure to antigens. Upon antigen exposure, these molecules are secreted allowing the immune system to recognize and effectively respond to a myriad of pathogens. Immunoglobulin or antibody secreting cells are the mature form of B lymphocytes, which during their development undergo gene rearrangements and selection in the bone marrow ultimately leading to the generation of B cells, each expressing a single antigen-specific receptor/immunoglobulin molecule. Each individual immunoglobulin molecule has an affinity for a unique motif, or epitope, found on a given antigen. When presented with an antigen, activated B cells differentiate into either plasma cells (which secrete large amounts of antibody that is specific for the inducing antigen), or memory B cells (which are long-lived and elicit a stronger and faster response if the host is re-exposed to the same antigen). The secreted form of immunoglobulin, when bound to an antigen, serves as an effector molecule that directs other cells of the immune system to facilitate the neutralization of soluble antigen or the eradication of the antigen-expressing pathogen. This review will focus on the regulation of secreted immunoglobulin by long-lived normal or disease-associated plasma. Specifically, the focus will be on signaling and transcriptional events that regulate the development and homeostasis of long-lived immunoglobulin secreting plasma cells.

  16. Factors Regulating Immunoglobulin Production by Normal and Disease-Associated Plasma Cells

    PubMed Central

    Jackson, David A.; Elsawa, Sherine F.

    2015-01-01

    Immunoglobulins are molecules produced by activated B cells and plasma cells in response to exposure to antigens. Upon antigen exposure, these molecules are secreted allowing the immune system to recognize and effectively respond to a myriad of pathogens. Immunoglobulin or antibody secreting cells are the mature form of B lymphocytes, which during their development undergo gene rearrangements and selection in the bone marrow ultimately leading to the generation of B cells, each expressing a single antigen-specific receptor/immunoglobulin molecule. Each individual immunoglobulin molecule has an affinity for a unique motif, or epitope, found on a given antigen. When presented with an antigen, activated B cells differentiate into either plasma cells (which secrete large amounts of antibody that is specific for the inducing antigen), or memory B cells (which are long-lived and elicit a stronger and faster response if the host is re-exposed to the same antigen). The secreted form of immunoglobulin, when bound to an antigen, serves as an effector molecule that directs other cells of the immune system to facilitate the neutralization of soluble antigen or the eradication of the antigen-expressing pathogen. This review will focus on the regulation of secreted immunoglobulin by long-lived normal or disease-associated plasma cells. Specifically, the focus will be on signaling and transcriptional events that regulate the development and homeostasis of long-lived immunoglobulin secreting plasma cells. PMID:25615546

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

    PubMed Central

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

    1990-01-01

    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. Images PMID:2304473

  18. [Occurrence of various immunoglobulin isotopes in horses with equine recurrent uveitis (ERU)].

    PubMed

    Eule, J C; Wagner, B; Leibold, W; Deegen, E

    2000-06-01

    We investigated 30 healthy eyes and 41 eyes with ERU from 57 horses. The total immunoglobulin titers and titers of IgGa, IgGb, IgM were measured in aqueous humour, vitreous and serum using different ELISA techniques. Every sample investigated contained detectable amounts of immunoglobulins. Compared to control eyes significantly increased titers were found in the aqueous humour and vitreous of the ERU eyes for all immunoglobulin isotypes studied (p < or = 0.01). While IgM was detected in only 2 out of thirty aqueous humour and in none of the thirty vitreous samples of healthy eyes, 79.6% of samples of ERU eyes revealed considerable IgM titers. Changes of the IgGa/IgGb ratio in the eye as compared to that in the autologous serum was more frequent in affected than in healthy eyes. In contrast to the intraocular immunoglobulins there were no significant differences in immunoglobulin serum titers in healthy horses and those affected with ERU (p > 0.05). In conclusion, the results argue for a physiological appearance of immunoglobulins in the healthy eye. The increased titers of immunoglobulins in eyes stricken with ERU might be signs either of a local ocular production of antibodies and/or an increased permeability of intraocular barriers.

  19. 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

  20. Organization, complexity and allelic diversity of the porcine (Sus scrofa domestica) immunoglobulin lambda locus.

    PubMed

    Schwartz, John C; Lefranc, Marie-Paule; Murtaugh, Michael P

    2012-05-01

    We have characterized the organization, complexity, and expression of the porcine (Sus scrofa domestica) immunoglobulin lambda (IGL) light chain locus, which accounts for about half of antibody light chain usage in swine, yet is nearly totally unknown. Twenty-two IGL variable (IGLV) genes were identified that belong to seven subgroups. Nine genes appear to be functional. Eight possess stop codons, frameshifts, or both, and one is missing the V-EXON. Two additional genes are missing an essential cysteine residue and are classified as ORF (open reading frame). The IGLV genes are organized in two distinct clusters, a constant (C)-proximal cluster dominated by genes similar to the human IGLV3 subgroup, and a C-distal cluster dominated by genes most similar to the human IGLV8 and IGLV5 subgroups. Phylogenetic analysis reveals that the porcine IGLV8 subgroup genes have recently expanded, suggesting a particularly effective role in immunity to porcine-specific pathogens. Moreover, expression of IGLV genes is nearly exclusively restricted to the IGLV3 and IGLV8 genes. The constant locus comprises three tandem cassettes comprised of a joining (IGLJ) gene and a constant (IGLC) gene, whereas a fourth downstream IGLJ gene has no corresponding associated IGLC gene. Comparison of individual BACs generated from the same individual revealed polymorphisms in IGLC2 and several IGLV genes, indicating that allelic variation in IGLV further expands the porcine antibody light chain repertoire.

  1. Natural killer cells, killer immunoglobulin-like receptors and human leucocyte antigen class I in disease

    PubMed Central

    Boyton, R J; Altmann, D M

    2007-01-01

    Natural killer cells constitute a potent, rapid part of the innate immune response to infection or transformation, and also generate a link to priming of adaptive immunity. Their function can encompass direct cytotoxicity as well as the release of cytokines and chemokines. In humans, a major component of natural killer (NK) cell target recognition depends mainly on the surveillance of human leucocyte antigen (HLA) class I molecules by killer immunoglobulin-like receptors (KIR). Different KIR can transmit inhibitory or activatory signals to the cell, and effector function is considered to result from the balance of these contributing signals. The regulation of NK cell responses depends on a number of variables: KIR genotype, HLA genotype, heterozygosity versus homozygosity for these, whether there is cognate recognition between the HLA and KIR products carried by an individual, clonal variation between individual NK cells in KIR expression, and the specific modulation of HLA expression by infection, transformation or peptide binding. Different HLA/KIR genotypes can impart different thresholds of activation to the NK cell repertoire and such genotypic variation has been found to confer altered risk in a number of diseases including human immunodeficiency virus (HIV) susceptibility and progression, hepatitis C virus clearance, idiopathic bronchiectasis, autoimmunity and cancer. PMID:17521317

  2. Molecular cloning and nucleotide sequencing of human immunoglobulin epsilon chain cDNA.

    PubMed Central

    Seno, M; Kurokawa, T; Ono, Y; Onda, H; Sasada, R; Igarashi, K; Kikuchi, M; Sugino, Y; Nishida, Y; Honjo, T

    1983-01-01

    DNA complementary to mRNA of human immunoglobulin E heavy chain (epsilon chain) isolated and purified from U266 cells has been synthesized and inserted into the PstI site of pBR322 by G-C tailing. This recombinant plasmid was used to transform E. coli chi 1776 to screen 1445 tetracycline resistant colonies. Nine clones (pGETI - 9) containing cDNA coding for the human epsilon chain were recognized by colony hybridization and Southern blotting analysis with a nick-translated human IgE genome fragment. The nucleotide sequence of the longest cDNA contained in pGET2 was determined. The results indicate that the sequence of 1657 nucleotides codes for 494 amino acids covering a part of the variable region and all of the constant region of the human epsilon chain. Most of the amino acid sequence deduced from the nucleotide sequence is in substantial agreement with that reported. Furthermore a termination codon after the -COOH terminal amino acid marks the beginning of a 3' untranslated region of 125 nucleotides with a poly A tail. Taking this into account, the structure of the human epsilon chain mRNA, except a part of the 5' end, is conserved fairly well in the cDNA insert in pGET2. Images PMID:6300763

  3. Solid-state NMR chemical shift assignments for AL-09 VL immunoglobulin light chain fibrils.

    PubMed

    Piehl, Dennis W; Blancas-Mejía, Luis M; Ramirez-Alvarado, Marina; Rienstra, Chad M

    2017-04-01

    Light chain (AL) amyloidosis is a systemic disease characterized by the formation of immunoglobulin light-chain fibrils in critical organs of the body. The light-chain protein AL-09 presents one severe case of cardiac AL amyloidosis, which contains seven mutations in the variable domain (VL) relative to its germline counterpart, κI O18/O8 VL. Three of these mutations are non-conservative-Y87H, N34I, and K42Q-and previous work has shown that they are responsible for significantly reducing the protein's thermodynamic stability, allowing fibril formation to occur with fast kinetics and across a wide-range of pH conditions. Currently, however, there is extremely limited structural information available which explicitly describes the residues that are involved in supporting the misfolded fibril structure. Here, we assign the site-specific (15)N and (13)C chemical shifts of the rigid residues of AL-09 VL fibrils by solid-state NMR, reporting on the regions of the protein involved in the fibril as well as the extent of secondary structure.

  4. 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.

  5. Three transposed elements in the intron of a human VK immunoglobulin gene.

    PubMed

    Straubinger, B; Osterholzer, E; Zachau, H G

    1987-11-25

    Two gene segments coding for the variable region of human immunoglobulin light chains of the kappa type (VK genes, ref. 2) were found to have unusual structures. The two genes which are called A6 and A22 are located in duplicated gene clusters. Their restriction maps are very similar. About 4 kb of the A22 gene region were sequenced. It turned out that the intron contains an insert with the characteristics of a transposed element. The inserted DNA of 1.2 kb length contains imperfect direct and inverted repeats at its ends; at the insertion site a duplication of five nucleotides was found. Within the inserted DNA one copy each of an Alu element and of the simple sequence motif (T-G)17 were identified. Also these two repetitive sequences are themselves flanked by short direct repeats. The major inserted DNA has no significant homology to published human nucleic acid sequences. The whole structure is interpreted best by assuming a sequential insertion of the three elements. The coding region of the VK gene itself has several mutations which by themselves would render it a pseudogene; we assume that the insertion event(s) occurred prior to the mutations. According to mapping and hybridization data A6 is very similar to A22.

  6. The human VK locus. Characterization of a duplicated region encoding 28 different immunoglobulin genes.

    PubMed

    Straubinger, B; Huber, E; Lorenz, W; Osterholzer, E; Pargent, W; Pech, M; Pohlenz, H D; Zimmer, F J; Zachau, H G

    1988-01-05

    Two large regions of the human multigene family coding for the variable parts of the immunoglobulin light chains of the K type (VK) have been characterized on cosmid clones. The two germline regions, called Aa and Ab, span together 250,000 base-pairs and comprise 28 different VK gene segments, nine of which have been sequenced. There is a preponderance of VKII genes but genes belonging to subgroups I and III, and genes that cannot be easily assigned to one of the known subgroups, are interspersed within the VKII gene clusters. A number of pseudogenes have been identified. Within the Aa and Ab regions, all gene segments are organized in the same transcriptional orientation. The regions Aa and Ab, whose restriction maps are highly homologous, were shown not to be allelic structures; they must have arisen by a duplication event. Taken together with previous results, one can conclude that the major part of the VK locus exists in duplicated form. One individual has been found who has only one copy of some of the duplicated regions. By chromosomal walking, the A regions could be linked to the O regions, an analysis of which has been reported. The A regions contribute about one-third of the VK genes so far identified.

  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. [Immunoglobulin G4 (IgG4)-related disease. A review of head and neck manifestations].

    PubMed

    Agaimy, A; Ihrler, S

    2014-03-01

    Immunoglobulin G4 (IgG4)-related disease (also known as hyper-IgG4 disease) is a recently defined emerging condition with highly heterogeneous clinicopathological features and variable disease manifestations. This disorder is characterized by unifocal or multifocal (multiorgan) involvement by tumefactive plasma cell-rich inflammatory infiltrates associated with prominent fibrosclerosis. This not uncommonly interferes with organ function resulting in diverse clinical symptoms. The autoimmune pancreatitis represents the prototype of this disease; however, to date almost all organs have been reported to be involved in this disorder. In the head and neck area several presentations of this disease may be encountered in salivary glands, lacrimal glands, thyroid gland, lymph nodes, soft tissue of the neck, ear and sinonasal tract. However, IgG4 positive plasma cells are occasionally prominent in non-specific chronic inflammatory conditions of the head and neck and the oral cavity unrelated to autoimmune diseases or systemic disorders, thus representing diagnostic pitfalls. The diagnosis of IgG4-related disease should be based on a combination of typical histological, clinical and serological findings.

  9. Change-O: a toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data

    PubMed Central

    Gupta, Namita T.; Vander Heiden, Jason A.; Uduman, Mohamed; Gadala-Maria, Daniel; Yaari, Gur; Kleinstein, Steven H.

    2015-01-01

    Summary: Advances in high-throughput sequencing technologies now allow for large-scale characterization of B cell immunoglobulin (Ig) repertoires. The high germline and somatic diversity of the Ig repertoire presents challenges for biologically meaningful analysis, which requires specialized computational methods. We have developed a suite of utilities, Change-O, which provides tools for advanced analyses of large-scale Ig repertoire sequencing data. Change-O includes tools for determining the complete set of Ig variable region gene segment alleles carried by an individual (including novel alleles), partitioning of Ig sequences into clonal populations, creating lineage trees, inferring somatic hypermutation targeting models, measuring repertoire diversity, quantifying selection pressure, and calculating sequence chemical properties. All Change-O tools utilize a common data format, which enables the seamless integration of multiple analyses into a single workflow. Availability and implementation: Change-O is freely available for non-commercial use and may be downloaded from http://clip.med.yale.edu/changeo. Contact: steven.kleinstein@yale.edu PMID:26069265

  10. 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.

  11. 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.

  12. Role of the Egami Score in Predicting Intravenous Immunoglobulin Resistance in Kawasaki Disease Among Different Ethnicities.

    PubMed

    Loomba, Rohit S; Raskin, Alexander; Gudausky, Todd M; Kirkpatrick, Edward

    Early treatment with intravenous immunoglobulin (IVIG) is necessary to help reduce the risk of coronary artery abnormalities, such as coronary artery aneurysms and to help alleviate symptoms, in Kawasaki disease. Some patients, however, do not respond to an initial dose of IVIG and require additional doses. Prediction of these IVIG nonresponders may be of assistance in altering initial therapy to make it more effective. The Egami score has been validated in the Japanese population to predict IVIG nonresponders but has shown to be ineffective in US populations. This study evaluates the Egami score in a Midwest US population, subdividing patients by race and the diagnosis of typical or atypical type of Kawasaki disease. Patients were included in the study if they met criteria for Kawasaki disease and received IVIG in the inpatient setting. A total of 182 patients were studied, and in all studied groups, the Egami score had poor sensitivity at predicting IVIG nonresponders. Sensitivity of the score differed between races and differed between typical and atypical Kawasaki disease. The Egami score, as well as other systems, have been validated to predict IVIG nonresponders. These, however, lack sensitivity in the US population. Other scores developed in the United States have also lacked sensitivity, likely due to the absence of race or Kawasaki disease classification as variables. The development of a sensitive scoring system to predict IVIG nonresponders in US populations will require the incorporation of race and Kawasaki disease classification, factors that seem to alter IVIG response.

  13. Immunoglobulins and transient paraproteins in sera of patients with the Wiskott-Aldrich syndrome: a follow-up study.

    PubMed Central

    Radl, J; Dooren, L H; Morell, A; Skvaril, F; Vossen, J M; Uittenbogaart, C H

    1976-01-01

    Immunoglobulin levels of individual classes and IgG subclasses and the occurrence of homogeneous immunoglobulins--paraproteins--were studied longitudinally in the sera of three patients with the Wiskott-Aldrich syndrome; Common findings in all three patients were great variations in the immunoglobulin levels, restricted heterogeneity of the immunoglobulins, the frequent appearance of transient homogeneous immunoglobulins and the presence of serum antibodies against bovine milk proteins. A partial and selective deficiency involving mainly the T immune system is postulated as an explanation for these findings. Images Fig. 2 Fig. 3 Fig. 4 PMID:954233

  14. 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

  15. In vivo effects of antiserum to IgD on surface immunoglobulins, serum immunoglobulins and lymphocyte blastogenesis in rhesus monkeys.

    PubMed Central

    Martin, L N; Leslie, G A

    1979-01-01

    The effects of injecting monkeys with goat antiserum to IgD, the IgG fraction of that antiserum or normal goat serum (NGS) were compared. The subcutaneous injection of 4 ml/kg of the whole antiserum resulted in decreased percentages of lymphocytes with surface IgD or IgM lasting from day 1 through day 7 post-injection followed by substantial recovery on day 10. Lymphocytes from these animals were stimulated as indicated by the increased incorporation of 3H-TdR by cells placed in culture on days 7-21 post-injection. The increased blastogenesis occurred in rosette-depleted (B cell) populations and did not occur in rosette-enriched (T cell) preparations. Hypergammaglobulinaemia and increased concentration of serum IgG were first detected on day 10 postinjection, maximal on day 14 and were in decline by day 18. Injection of 4 ml/kg NGS did not alter the percentages of lymphocytes with surface immunoglobulins, result in hypergammaglobulinaemia, or stimulate the degree of blastogenesis observed after anti-IgD. Injection of the IgG fraction of the antiserum resulted in decreased lymphocytes with surface immunoglobulins but did not stimulate hypergammaglobulinaemia or increase blastogenesis. Injection of one monkey with the IgG fraction of anti-IgD combined with NGS resulted in increased serum IgG and increased blastogenesis. Both antibody to IgD and multiple antigenic challenge appear to be required for these responses. Images Figure 1 Figure 2 PMID:112042

  16. Immunogenicity of heterologous Fc and Fab immunoglobulin fragments in rabbits, guinea-pigs and rats

    PubMed Central

    Binaghi, R. A.; Oriol, R.; Boussac-Aron, Yolande

    1967-01-01

    Rabbits, guinea-pigs and rats were immunized with various heterologous 7S and 19S immunoglobulins from each other and man, and the antisera obtained were studied by immunoelectrophoresis. Rabbits produced antibodies against the Fc and the Fab fragments of the immunoglobulin injected, while guinea-pigs and rats only produced anti-Fc antibodies. The fact that guinea-pigs and rats only respond to the specific determinants of each class of immunoglobulin provides a simple method for the preparation of class-specific antisera. ImagesFIG. 1FIG. 2 PMID:6027784

  17. Repeat organization and epigenetic regulation of the DH-Cmu domain of the immunoglobulin heavy-chain gene locus.

    PubMed

    Chakraborty, Tirtha; Chowdhury, Dipanjan; Keyes, Amanda; Jani, Anant; Subrahmanyam, Ramesh; Ivanova, Irina; Sen, Ranjan

    2007-09-07

    The first steps of murine immunoglobulin heavy-chain (IgH) gene recombination take place within a chromosomal domain that contains diversity (D(H)) and joining (J(H)) gene segments, but not variable (V(H)) gene segments. Here we show that the chromatin state of this domain is markedly heterogeneous. Specifically, only 5'- and 3'-most D(H) gene segments carry active chromatin modifications, whereas intervening D(H)s are associated with heterochromatic marks that are maintained by ongoing histone deacetylation. The intervening D(H)s form part of a tandemly repeated sequence that expresses tissue-specific, antisense oriented transcripts. We propose that the intervening D(H) genes are actively suppressed by repeat-induced epigenetic silencing, which is reflected in their infrequent representation in DJ(H) junctions compared to the flanking D(H) genes.

  18. The effect of autogenic training on salivary immunoglobulin A in surgical patients with breast cancer: a randomized pilot trial.

    PubMed

    Minowa, Chika; Koitabashi, Kikuyo

    2014-11-01

    Psychological stress among breast cancer patients can inhibit immune function and contribute to disease progression. We investigated the effects of autogenic training (AT), a relaxation method for reducing stress, on salivary immunoglobulin A (sIgA) in breast cancer surgery patients. Thirty patients scheduled to undergo breast cancer surgery were randomly assigned to an AT or control group (usual care). Patients in the AT group underwent training for 7 days after surgery. Salivary IgA and heart rate variability were assessed on the day before surgery, and on the third and seventh postoperative days. Levels of sIgA were significantly higher on the seventh postoperative day in the AT group (n = 7) compared to the control group (n = 7) (p = 0.049). These findings suggest that AT may improve immune function in breast surgery patients.

  19. Cloning of size-selected human immunoglobulin heavy-chain rearrangements from third complementarity-determining region fingerprint profiles.

    PubMed

    Raaphorst, F M; Tami, J; Sanz, I E

    1996-01-01

    Methods have been developed to rapidly visualize the size distribution of third complementarity-determining regions (CDR3) in immunoglobulin (Ig) and T-cell receptor (TCR) molecules. DNA fragments spanning the Ig or TCR CDR3 are generated by PCR using primers at fixed positions in the variable and constant segments. These fragments differ in length due to size variation of the CDR3s. Visualization of the amplification products in polyacrylamide gels as a "CDR3 fingerprint profile" is a rough measure for the complexity of the Ig and TCR antigen-binding specificities. We report an adaptation of this method for the analysis of human Ig heavy-chain genes that incorporates silver staining, which allows for the fine analysis of specific regions of the profiles. This is especially useful for the study of low-abundant transcripts.

  20. 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.

  1. CODV-Ig, a universal bispecific tetravalent and multifunctional immunoglobulin format for medical applications

    PubMed Central

    Steinmetz, Anke; Vallée, François; Beil, Christian; Lange, Christian; Baurin, Nicolas; Beninga, Jochen; Capdevila, Cécile; Corvey, Carsten; Dupuy, Alain; Ferrari, Paul; Rak, Alexey; Wonerow, Peter; Kruip, Jochen; Mikol, Vincent; Rao, Ercole

    2016-01-01

    ABSTRACT Bispecific immunoglobulins (Igs) typically contain at least two distinct variable domains (Fv) that bind to two different target proteins. They are conceived to facilitate clinical development of biotherapeutic agents for diseases where improved clinical outcome is obtained or expected by combination therapy compared to treatment by single agents. Almost all existing formats are linear in their concept and differ widely in drug-like and manufacture-related properties. To overcome their major limitations, we designed cross-over dual variable Ig-like proteins (CODV-Ig). Their design is akin to the design of circularly closed repeat architectures. Indeed, initial results showed that the traditional approach of utilizing (G4S)x linkers for biotherapeutics design does not identify functional CODV-Igs. Therefore, we applied an unprecedented molecular modeling strategy for linker design that consistently results in CODV-Igs with excellent biochemical and biophysical properties. CODV architecture results in a circular self-contained structure functioning as a self-supporting truss that maintains the parental antibody affinities for both antigens without positional effects. The format is universally suitable for therapeutic applications targeting both circulating and membrane-localized proteins. Due to the full functionality of the Fc domains, serum half-life extension as well as antibody- or complement-dependent cytotoxicity may support biological efficiency of CODV-Igs. We show that judicious choice in combination of epitopes and paratope orientations of bispecific biotherapeutics is anticipated to be critical for clinical outcome. Uniting the major advantages of alternative bispecific biotherapeutics, CODV-Igs are applicable in a wide range of disease areas for fast-track multi-parametric drug optimization. PMID:26984268

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

    PubMed

    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.

  3. Killer immunoglobulin-like receptor repertoire analysis in a Caucasian Spanish cohort with inflammatory bowel disease.

    PubMed

    López-Hernández, Ruth; Campillo, Jose A; Legaz, Isabel; Valdés, Mariano; Salama, Hortensia; Boix, Francisco; Hernández-Martínez, A M; Eguia, Jorge; González-Martínez, G; Moya-Quiles, Maria R; Minguela, Alfredo; García-Alonso, Ana; Carballo, Fernando; Muro, Manuel

    2016-11-01

    Immunological molecules are implicated in inflammatory disorders, including inflammatory bowel disease (IBD; Crohn disease [CD] and ulcerative colitis [UC]). Killer cell immunoglobulin-like receptors (KIRs) are also genetically variable proteins involved in immune function. They are expressed by NK cells and certain T lymphocytes, regulate specificity and function by interaction with HLA Class I molecules, may be either inhibitory or activating and are polymorphic both in terms of alleles and haplotype gene content. Genetic associations between activating KIRs and certain autoimmune and inflammatory diseases have been reported; however, a possible association between KIR and IBD remains unclear. The aim of this study was to determine the relationship between KIR repertoire and IBD pathologies in a Spanish cohort. KIR variability was analyzed using PCR-sequence specific oligonucleotide probes (SSOP). Inhibitory KIR2DL5 was found more frequently in UC and IBD patient groups than in healthy controls (P = 0.028 and P = 0.01, respectively), as was activating KIR2DS1 (P = 0.02, Pc > 0.05, UC vs. Controls; P = 0.001, Pc = 0.01, IBD vs Controls; P = 0.01, Pc > 0.05, Controls vs CR), KIR2DS5 (P = 0.0028, Pc = 0.04, Controls vs UC; P = 0.0001, Pc = 0.0017, Controls vs IBD; P = 0.01, Pc > 0.05, Controls vs CD) and KIR3DS1 (P = 0.012, Pc > 0.05, Controls vs IBD). Our data suggest that imbalance between activating and inhibitory KIR may partially explain the different pathogeneses of these IBDs and that there is a hypothetical role for the telomeric B region (which contains both KIR2DS5 and KIR2DS1) in these diseases.

  4. 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

  5. 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.

  6. 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.

  7. Lymphocyte Surface Markers and Serum Immunoglobulins in Persons with Down's Syndrome.

    ERIC Educational Resources Information Center

    And Others; Hann, Hie-Won L.

    1979-01-01

    Distributions of the serum immunoglobulins (IgM), of T and B lymphocytes, and subpopulations of B lymphocytes were studied in children and institutionalized adults with Down's syndrome and appropriate mentally retarded controls. (Author)

  8. Challenges in vaccinating infants born to mothers taking immunoglobulin biologicals during pregnancy.

    PubMed

    Ling, Juejing; Koren, Gideon

    2016-01-01

    While immunoglobulin biologicals are increasingly used during pregnancy, there have been concerns on the immune function and vaccination of infants born to mothers taking immunoglobulin biologicals. In addition to the detection of biologicals in cord blood, cases of severe neonatal neutropenia and fatal dissemination of Bacillus Calmette-Guérin (BCG) have been reported. With increasing number of infants exposed to immunoglobulin biologicals in utero, there is a need to address the challenges in vaccinating these infants. This review summarizes the available evidence to discuss the issues of immunoglobulin biological exposure in utero, neonatal immune function, long-term immune development, and the challenges and strategies of vaccinating newborns and infants who were born to mothers taking biologicals during pregnancy.

  9. 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.

  10. [Determination of immunoglobulin fractions in the blood serum of El Tor cholera patients and carriers].

    PubMed

    Pokrovskiĭ, V I; Reshetniak, T V; Bol'shakova, N Ia; Stefani, D V

    1975-01-01

    The authors present the results of examination of patients and carriers of El Tor vibrios for the purpose of detection in their blood sera of individual immunoglobulin fractions. The content of three immunoglobulin fractions (A, G and M) was determined by radial immunodiffusion after Mancini in 118 blood sera of 50 patients with cholera and in 61 sera from 31 vibrio carriers. Blood sera of 23 apparently healthy persons were examined for control. It was found that in cholera patients the level of all the immunoglobulin classes was much greater than in healthy individuals; at the period of convalescence the IgA content increased, and the IgM content decreased. The blood sera of vibrio carriers displayed an equally high IgA and IgG level. There was no significant difference in the immunoglobulin indices in patients with a different severity of the disease.

  11. [Comparison of two methods for determining G, A, M immunoglobulins (spectrophotometry and radial immunodiffusion)].

    PubMed

    Gamaleia, N B; Mondrus, K A

    1994-01-01

    Blood serum levels of immunoglobulins A, G, and M were measured by two methods, spectrophotometry and radial immunodiffusion. The results were in good correlation, this permitting the authors recommend spectrophotometry as a simpler and more objective method for such measurements.

  12. Immunoglobulins in tracheo-bronchial secretion with special reference to IgE

    PubMed Central

    Deuschl, H.; Johansson, S. G. O.

    1974-01-01

    Quantitative measurements of immunoglobulins E, A and G were made in tracheobronchial secretion and serum of thirty-four patients in association with bronchoscopy. Measurable quantities of all three immunoglobulins were found in both secretion and serum in all patients, except in one person, in whom IgA was found neither in the secretion nor the serum, and in another person in whom no measurable IgG was found in the secretion. Calculations indicated that all immunoglobulins were produced locally in the tracheo-bronchial mucosa. This applied especially to IgA and IgE, of which 84 and 73% respectively, were calculated to have been produced locally. Quantitative differences between the three immunoglobulins were also apparent between different groups of patients. The number of patients studied is too small, however, for definite conclusions to be drawn in this respect. PMID:4468847

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

    PubMed Central

    Kidson-Gerber, Giselle

    2015-01-01

    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

  14. Ashtekar variables

    NASA Astrophysics Data System (ADS)

    Ashtekar, Abhay

    2015-05-01

    In the spirit of Scholarpedia, this invited article is addressed to students and younger researchers. It provides the motivation and background material, a summary of the main physical ideas, mathematical structures and results, and an outline of applications of the connection variables for general relativity. These variables underlie both the canonical/Hamiltonian and the spinfoam/path integral approaches in loop quantum gravity.

  15. Phase I-II study of isotopic immunoglobulin therapy for primary liver cancer

    SciTech Connect

    Ettinger, D.S.; Order, S.E.; Wharam, M.D.; Parker, M.K.; Klein, J.L.; Leichner, P.K.

    1982-02-01

    A phase I-II study of isotopic immunoglobulin therapy was performed in 18 patients with primary liver cancer; 14 were evaluable for toxicity. The patients received a dose of 37-157 millicuries of 131I-labeled antibody. The dose-limiting factor appears to be hematologic toxicity, especially thrombocytopenia. An objective antitumor effect was seen in six of nine patients who were evaluable for response. Present results suggest that further clinical studies with isotopic immunoglobulin are indicated.

  16. Immunohistochemical study of expression of immunoglobulins in canine B-cell lymphomas.

    PubMed

    Sokołowska, J; Micuń, J; Zabielska, K; Malicka, E; Lechowski, R

    2010-01-01

    Nineteen canine lymphomas were included in this study. Tumors were classified according to the updated Kiel classification adapted for canine lymphomas by Fournel-Fleury et al. Immunoglobulin light chains (kappa and lambda) and IgM and IgG expression were determined by immunohistochemical method. In all examined cases neoplastic cells were positive for one of the immunoglobulin light chains. Expression of lambda light chains and kappa light chains was observed in 18/19 and 1/19 tumors, respectively. In the majority of neoplastic cells in each examined specimen this reaction had a membranous pattern (skappa/slambda). In all examined cases the presence of immunoglobulin light chains was also observed in the cytoplasm of some neoplastic cells (ckappa/clambda). These cells were usally rare and never constituted a dominant population. The expression of immunoglobulin was found in 13/19 cases. Most lymphomas were sIgM positive (11/13 cases). In one case expression of IgG was found, and in another lymphoma two populations of neoplastic cells with different expression of examined immunoglobulins (cells with IgM+ and IgG+ phenotypes) were observed. The reaction also had a membranous pattern. The cells containing cytoplasmic immunoglobulins were rare, and in most cases were of the same type as the surface immunoglobulins. Our study has confirmed that canine lymphomas are a monoclonal proliferation of B-cells usually expressing immunoglobulin lambda light chains and that the vast majority of tumors deriving from B-cells express IgM. Our study also indicates a possibility of occurence of biclonal lymphomas in canine species.

  17. [Immunoglobulin and electrolyte levels in sialadenosis of the parotid (author's transl)].

    PubMed

    Proescher, H J

    1975-03-01

    A comparison of 15 patients with sialadenosis of the parotid gland and 15 control patients was made of their levels of immunoglobulins A, G and M, sodium, potassium, calcium, chloride, albumin, inorganic phosphate, cholesterin, uric acid and creatinin. Those patients with sialadenosis, in comparison with the control group and the findings in other reports, show reduced immunoglobulin A and increased potassium in the parotic secretion. The disturbance of function of the acinic cell is discussed.

  18. LOX-1 dependent overexpression of immunoglobulins in cardiomyocytes in response to angiotensin II.

    PubMed

    Kang, Bum-Yong; Hu, Changping; Prayaga, Sastry; Khaidakov, Magomed; Sawamura, Tatsuya; Seung, Ki-Bae; Mehta, Jawahar L

    2009-02-06

    LOX-1, a cell surface lectin-like receptor, is upregulated by oxidized low-density lipoprotein (ox-LDL) and angiotensin II (Ang II), and plays an important role in host defense. The specific C-type lectin domain on LOX-1 is essential for ox-LDL binding and internalization, generation of oxidant species and eliciting immune response. Here, we show that LOX-1 deletion alters genes that relate to immune response. Microarray (and qPCR) analysis of cardiac tissues showed downregulated expression of several immunoglobulins (Igk-V8, Igk-C, Igh-6, Igj, Ighg, Igh, and Igl-V1) in the LOX-1 knockout (KO) mice [p<0.05 vs. the wild-type (WT) mice]. The expression of these immunoglobulins was upregulated several-fold in the LOX-1 KO mice hearts when these mice were infused with Ang II (p<0.05, vs. WT mice). Importantly, cultured mouse HL-1 cardiomyocytes expressed these immunoglobulins, and pretreatment of cardiomyocytes with a specific anti-LOX-1 antibody enhanced the generation of immunoglobulins upon subsequent exposure to Ang II. These observations mirrored the data obtained from WT and LOX-1 KO mice hearts in the resting state and following Ang II infusion. This study provides first set of data on immunoglobulin expression in cardiac tissues of WT and LOX-1 KO mice and in cultured HL-1 cardiomyocytes, and demonstrates that LOX-1 inactivation leads to upregulation of immunoglobulins in cardiomyocytes upon challenge with Ang II.

  19. Subcutaneous immunoglobulin in CIDP and MMN: a short-term nationwide study.

    PubMed

    Cocito, Dario; Merola, Aristide; Peci, Erdita; Mazzeo, Anna; Fazio, Raffaella; Francia, Ada; Valentino, Paola; Liguori, Rocco; Filosto, Massimiliano; Siciliano, Gabriele; Clerici, Angelo Maurizio; Lelli, Stefania; Marfia, Girolama Alessandra; Antonini, Giovanni; Cecconi, Ilaria; Nobile-Orazio, Eduardo; Lopiano, Leonardo

    2014-11-01

    This multi-center Italian prospective observational study reports the 4 months follow-up data of 87 patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) shifted from intravenous to subcutaneous immunoglobulin treatment. A therapeutic shift from intravenous to subcutaneous immunoglobulin was performed in 87 patients (66 CIDP; 21 MMN) affected by immune-mediated peripheral neuropathies with evidence of a sustained clinical response to intravenous immunoglobulin. Patients were evaluated by means of the Overall Neuropathy Limitation Scale, Medical Research Council Scale and Life Quality Index questionnaire, both at the time of therapeutic shift and after 4 months of subcutaneous immunoglobulin treatment. A sustained clinical efficacy was observed after the switch to subcutaneous immunoglobulin: the Overall Neuropathy Limitation Scale score improved in the group of 66 CIDP patients (P = 0.018), with only one subject reporting a worsening of 1 point, and remained stable in the group of 21 MMN patients (P = 0.841), with one subject reporting a worsening of two points. An improvement in the patient's perception of therapeutic setting was reported in both groups. This large multi-center study confirms the short-term clinical equivalence of subcutaneous versus intravenous immunoglobulin and a possible improvement in the patient's perception of therapeutic setting with the subcutaneous administration. However, further studies are required to extend the results to a longer observational period.

  20. Identification of immunoglobulins using Chou's pseudo amino acid composition with feature selection technique.

    PubMed

    Tang, Hua; Chen, Wei; Lin, Hao

    2016-04-01

    Immunoglobulins, also called antibodies, are a group of cell surface proteins which are produced by the immune system in response to the presence of a foreign substance (called antigen). They play key roles in many medical, diagnostic and biotechnological applications. Correct identification of immunoglobulins is crucial to the comprehension of humoral immune function. With the avalanche of protein sequences identified in postgenomic age, it is highly desirable to develop computational methods to timely identify immunoglobulins. In view of this, we designed a predictor called "IGPred" by formulating protein sequences with the pseudo amino acid composition into which nine physiochemical properties of amino acids were incorporated. Jackknife cross-validated results showed that 96.3% of immunoglobulins and 97.5% of non-immunoglobulins can be correctly predicted, indicating that IGPred holds very high potential to become a useful tool for antibody analysis. For the convenience of most experimental scientists, a web-server for IGPred was established at http://lin.uestc.edu.cn/server/IGPred. We believe that the web-server will become a powerful tool to study immunoglobulins and to guide related experimental validations.

  1. Preserved levels of uninvolved immunoglobulins are independently associated with favorable outcome in patients with symptomatic multiple myeloma.

    PubMed

    Kastritis, E; Zagouri, F; Symeonidis, A; Roussou, M; Sioni, A; Pouli, A; Delimpasi, S; Katodritou, E; Michalis, E; Michael, M; Hatzimichael, E; Vassou, A; Repousis, P; Christophoridou, A; Kartasis, Z; Stefanoudaki, E; Megalakaki, C; Giannouli, S; Kyrtsonis, M-C; Konstantopoulos, K; Spyroupoulou-Vlachou, M; Terpos, E; Dimopoulos, M A

    2014-10-01

    Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P<0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618-0.987, P=0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P<0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival.

  2. Atopic dermatitis: serum immunoglobulins and T-lymphocyte subpopulations.

    PubMed

    Valdés Sánchez, A F; Gómez Echevarría, A H; Lastra Alfonso, G

    1991-04-01

    A group of patients with atopic dermatitis who attended the Allergy Outpatient Service of the Hermanos Ameijeiras Clinical Surgical Hospital from May, 1987 to May, 1988 were studied. The patients were assigned to 2 groups; the first one composed of 38 patients and the second one composed of 12 non-allergic, supposedly healthy subjects. Different tests were carried out for the quantification of total serum immunoglobulins (A, G, M, E) by means of the radial immunodiffusion method and the ELISA ultramicromethod. They were also submitted to quantification of lymphocyte subpopulations by means of the indirect immunofluorescence test with monoclonal antibodies, using Cuban antiserum prepared at the National Institute of Oncology and Radiobiology. In our study IgG and IgA values were within normal limits in patients, contrary to the statistically significant increase in IgM and IgE values. The relative values of total T-lymphocytes (anti-T3) and of the suppressor lymphocyte subpopulations decreased.

  3. Short communication: Immunoglobulin variation in quarter-milked colostrum.

    PubMed

    Baumrucker, Craig R; Stark, Andrea; Wellnitz, Olga; Dechow, Chad; Bruckmaier, Rupert M

    2014-01-01

    Whereas whole first-milked colostrum IgG1 variation is documented, the IgG1 difference between the quarter mammary glands of dairy animals is unknown. First colostrum was quarter-collected from healthy udders of 8 multiparous dairy cows, all within 3h of parturition. Weight of colostrum produced by individual quarters was determined and a sample of each was frozen for subsequent analysis. Immunoglobulin G1 concentration (mg/mL) was measured by ELISA and total mass (g) was calculated. Standard addition method was used to overcome colostrum matrix effects and validate the standard ELISA measures. Analysis of the data showed that cow and quarter (cow) were significantly different in both concentration and total mass per quarter. Analysis of the mean IgG1 concentration of the front and rear quarters showed that this was not different, but the large variation in individual quarters confounds the analysis. This quarter difference finding indicates that each mammary gland develops a different capacity to accumulate precolostrum IgG1, whereas the circulating hormone concentrations that induce colostrogenesis reach the 4 glands similarly. This finding also shows that the variation in quarter colostrum production is a contributor to the vast variation in first milking colostrum IgG1 content. Finally, the data suggests other factors, such as locally acting autocrine or paracrine, epigenetic, or stochasticity, in gene regulation mechanisms may impinge on colostrogenesis capacity.

  4. Autonomic Neurotransmitters Modulate Immunoglobulin A Secretion in Porcine Colonic Mucosa

    PubMed Central

    Schmidt, Lisa D.; Xie, Yonghong; Lyte, Mark; Vulchanova, Lucy; Brown, David R.

    2007-01-01

    Secretory immunoglobulin A (sIgA) plays a crucial role in mucosal surface defense. We tested the hypothesis that colonic sIgA secretion is under enteric neural control. Immunohistochemistry of the porcine distal colonic mucosa revealed presumptive cholinergic and adrenergic nerve fibers apposed to secretory component (SC)-positive crypt epithelial cells and neighboring IgA+ plasmacytes. The cholinomimetic drug carbamylcholine elicited rapid, atropine-sensitive IgA secretion into the luminal fluid bathing mucosal explants mounted in Ussing chambers. The adrenergic receptor agonist norepinephrine also increased IgA secretion, an action inhibited by phentolamine. These effects were independent of agonist-induced anion secretion. In Western blots of luminal fluid, both agonists increased the density of protein bands co-immunoreactive for IgA and SC. Mucosal exposure to enterohemorrhagic Escherichia coli did not affect IgA secretion, and carbamylcholine treatment did not affect mucosal adherence of this enteropathogen. Acetylcholine and norepinephrine, acting respectively through muscarinic cholinergic and alpha-adrenergic receptors in the colonic mucosa, stimulate sIgA secretion and may enhance mucosal defense in vivo. PMID:17320195

  5. Measles and Other Virus-specific Immunoglobulins in Multiple Sclerosis

    PubMed Central

    Haire, Margaret; Fraser, K. B.; Millar, J. H. D.

    1973-01-01

    Immunoglobulins M and G specific for meales, herpes simplex, and rubella viruses were assayed by the fluorescent antibody method in sera and cerebrospinal fluids (C.S.F.) obtained simultaneously from 30 patients with multiple sclerosis, 30 patients with other neurological diseases, and 30 “normal” control subjects. Sera of 11 out of 30 patients with multiple sclerosis had IgM which reacted specifically with measles virus-infected cells, compared with 2 out of 30 of the patients with other neurological diseases and none of the 30 normal controls. Virus-specific IgM was not found in C.S.F. by this method. The geometric mean titre of measles virus-specific IgG in serum was significantly higher in the multiple sclerosis group than in either control group, and while IgG specific for all three viruses was found in C.S.F., suggesting transfer across the blood-brain barrier, measles IgG predominated. ImagesFIG. 1FIG. 2 PMID:4356870

  6. Measles and other virus-specific immunoglobulins in multiple sclerosis.

    PubMed

    Haire, M; Fraser, K B; Millar, J H

    1973-09-22

    Immunoglobulins M and G specific for meales, herpes simplex, and rubella viruses were assayed by the fluorescent antibody method in sera and cerebrospinal fluids (C.S.F.) obtained simultaneously from 30 patients with multiple sclerosis, 30 patients with other neurological diseases, and 30 "normal" control subjects. Sera of 11 out of 30 patients with multiple sclerosis had IgM which reacted specifically with measles virus-infected cells, compared with 2 out of 30 of the patients with other neurological diseases and none of the 30 normal controls. Virus-specific IgM was not found in C.S.F. by this method.The geometric mean titre of measles virus-specific IgG in serum was significantly higher in the multiple sclerosis group than in either control group, and while IgG specific for all three viruses was found in C.S.F., suggesting transfer across the blood-brain barrier, measles IgG predominated.

  7. Immunoglobulin G1 Fc domain motions: implications for Fc engineering

    PubMed Central

    Frank, Martin; Walker, Ross C.; Lanzilotta, William N.; Prestegard, James H.; Barb, Adam W.

    2014-01-01

    The fragment crystallizable (Fc) region links the key pathogen identification and destruction properties of immunoglobulin G(IgG). Pathogen opsonization positions Fcs to activate pro-inflammatory Fcγ receptors (FcγRs) on immune cells. The cellular response and committal to a damaging, though protective, immune response is tightly controlled at multiple levels. Control mechanisms are diverse and in many cases unclear, but one frequently suggested contribution originates in Fcγ receptor affinity being modulated through shifts in Fc conformational sampling. Here we report a previously unseen IgG1 Fc conformation. This observation motivated an extensive molecular dynamics (MD) investigation of polypeptide and glycan motions that revealed greater amplitude of motion for the N-terminal Cγ2 domains and N-glycan than previously observed. Residues in the Cγ2/Cγ3 interface and disulphide-bonded hinge were identified as influencing the Cγ2 motion. Our results are consistent with a model of Fc that is structurally dynamic. Conformational states that are competent to bind immune-stimulating FcγRs interconverted with Fc conformations distinct from those observed in FcγR complexes, which may represent a transient, nonbinding population. PMID:24522230

  8. Intrahepatic synthese of immunoglobulin G in chronic liver disease.

    PubMed

    Kronborg, I J; Knopf, P M

    1980-04-01

    A method has been developed to measure the in vitro production of immunoglobulin (Ig) by liver biopsy specimens. Five to 30 mg of liver tissue was cultured for 24 h in Dulbecco's modified Eagle's medium/10% foetal calf serum (FCS) containing radiolabelled leucine (L-[4,5-3H] leucine). The culture medium was collected, centrifuged and the supernatant dialysed to remove labelled leucine. The residual radioactivity was a measure of newly synthesized 3H-labelled proteins released into the medium. The quantity of IgG was determined by immunoprecipitation with monospecific antisera to IgG heavy chains. The presence of IgG in the supernatant was confirmed by chromatography on protein-A Sepharose column. In 6 biopsies without evidence of active inflammation (4 normal and 2 fatty liver by histological criteria) less than 1% of the protein synthesized was IgG. In contrast in the presence of active inflammation in 4 cases of alcoholic hepatitis the IgG percentage ranged from 2 to 6%. Maximal levels of IgG production were detected in 3 cases of chronic active hepatitis (CAH) and ranged from 5 to 30%. The increased Ig synthesis by the liver in alcoholic hepatitis and CAH is presumed to be an index of the intrahepatic host response and may have important implications for mechanisms of liver damage in these diseases.

  9. Neutralizing activities against seasonal influenza viruses in human intravenous immunoglobulin

    PubMed Central

    Onodera, Hiroyuki; Urayama, Takeru; Hirota, Kazue; Maeda, Kazuhiro; Kubota-Koketsu, Ritsuko; Takahashi, Kazuo; Hagiwara, Katsuro; Okuno, Yoshinobu; Ikuta, Kazuyoshi; Yunoki, Mikihiro

    2017-01-01

    Influenza viruses A/H1N1, A/H3N2, and B are known seasonal viruses that undergo annual mutation. Intravenous immunoglobulin (IVIG) contains anti-seasonal influenza virus globulins. Although the virus-neutralizing (VN) titer is an indicator of protective antibodies, changes in this titer over extended time periods have yet to be examined. In this study, variations in hemagglutination inhibition (HI) and VN titers against seasonal influenza viruses in IVIG lots over extended time periods were examined. In addition, the importance of monitoring the reactivity of IVIG against seasonal influenza viruses with varying antigenicity was evaluated. A/H1N1, A/H3N2, and B influenza virus strains and IVIG lots manufactured from 1999 to 2014 were examined. The HI titer was measured by standard methods. The VN titer was measured using a micro-focus method. IVIG exhibited significant HI and VN titers against all investigated strains. Our results suggest that the donor population maintains both specific and cross-reactive antibodies against seasonal influenza viruses, except in cases of pandemic viruses, despite major antigen changes. The titers against seasonal influenza vaccine strains, including past strains, were stable over short time periods but increased slowly over time. PMID:28331286

  10. 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.

  11. Case report: acute renal failure after administering intravenous immunoglobulin.

    PubMed

    Graumann, Aaron; Zawada, Edward T

    2010-03-01

    We report the case of an 87-year-old white woman with myasthenia gravis who presented with nausea, shortness of breath, azotemia, and hyperkalemia shortly after completing a course of intravenous immunoglobulin (IVIG). She had been receiving monthly transfusions of IVIG, but this time had received daily infusions for 5 days rather than 1 day. She had received this same dose in the past without incident. Her history was significant for coronary artery disease, atrial fibrillation, deep venous thrombosis, pulmonary embolism, chronic steroid use, and recurrent urinary tract infection. On examination, she was slightly confused, mildly dehydrated, had a grade II systolic ejection murmur along the upper left sternal border, had bilateral and symmetric mild weakness of the upper and lower extremities, and exhibited mild edema of the lower extremities. Before transfer from the emergency room, she was found to have an elevated serum urea nitrogen and creatinine of 55 and 5.8 mg/dL (19.6 mmol/L and 512.7 micromol/L, respectively). Creatinine 8 days earlier was 0.9 mg/dL (79.6 micromol/L). The hospital course of the acute renal failure is presented with a review of the literature on cases of acute renal failure after IVIG.

  12. The monocyte binding domain(s) on human immunoglobulin G.

    PubMed

    Woof, J M; Nik Jaafar, M I; Jefferis, R; Burton, D R

    1984-06-01

    Monocyte binding has previously been assigned to the C gamma 3 domain of human immunoglobulin G (IgG) largely on the ability of the pFc' fragment to inhibit the monocyte-IgG interaction. This ability is markedly reduced compared to the intact parent IgG. We find this result with a conventional pFc' preparation but this preparation is found to contain trace contamination of parent IgG as demonstrated by reactivity with monoclonal antibodies directed against C gamma 2 domain and light-chain epitopes of human IgG. Extensive immunoaffinity purification of the pFc' preparation removes its inhibitory ability indicating that this originates in the trace contamination of parent IgG (or Fc). Neither of the human IgG1 paraproteins TIM, lacking the C gamma 2 domain, or SIZ, lacking the C gamma 3 domain, are found to inhibit the monocyte-IgG interaction. The hinge-deleted IgG1 Dob protein shows little or no inhibitory ability. Indirect evidence for the involvement of the C gamma 2 domain in monocyte binding is considered. We suggest finally that the site of interaction is found either on the C gamma 2 domain alone or between the C gamma 2 and C gamma 3 domains.

  13. Specific immunoglobulin E in patients with immediate persulfate hypersensitivity.

    PubMed

    Aalto-Korte, Kristiina; Mäkinen-Kiljunen, Soili

    2003-07-01

    Persulfate salts may cause contact urticaria, allergic and irritant contact dermatitis, rhinitis and asthma. The mechanism of the immediate reactions has been unclear. Positive prick test, skin application and nasal and bronchial provocations identify immediate allergy. There is only 1 previous report of specific binding of immunoglobulin E (IgE) to ammonium persulfate demonstrated by radioallergosorbent test (RAST). In the present study, fresh 2% ammonium and potassium persulfate solutions were used for prick testing. Patients with positive prick tests were further evaluated with open skin application, immunospot and RAST. Prick testing with persulfate salts was performed in a total of 138 patients. 7 patients had a positive reaction to at least 1 persulfate salt. 6 of the patients had had skin symptoms, urticaria, eczema or angioedema, because of contact with hair bleaches. Open application on healthy skin was performed in 4 patients, and 3 out of them had urticarial reactions. The sera of 5 patients were investigated with immunospot and RAST. On immunospot, specific binding of IgE to human serum albumin (HSA)-conjugated ammonium and potassium persulfate was found in 2 patients. 1 immunospot-positive patient also had a positive RAST to ammonium persulfate-HSA conjugate. The mechanism of immediate hypersensitivity to persulfates thus seems to be IgE-mediated at least in some patients.

  14. Structural characterization of anti-inflammatory immunoglobulin G Fc proteins.

    PubMed

    Ahmed, Alysia A; Giddens, John; Pincetic, Andrew; Lomino, Joseph V; Ravetch, Jeffrey V; Wang, Lai-Xi; Bjorkman, Pamela J

    2014-09-09

    Immunoglobulin G (IgG) is a central mediator of host defense due to its ability to recognize and eliminate pathogens. The recognition and effector responses are encoded on distinct regions of IgGs. The diversity of the antigen recognition Fab domains accounts for IgG's ability to bind with high specificity to essentially any antigen. Recent studies have indicated that the Fc effector domain also displays considerable heterogeneity, accounting for its complex effector functions of inflammation, modulation, and immune suppression. Therapeutic anti-tumor antibodies, for example, require the pro-inflammatory properties of the IgG Fc to eliminate tumor cells, while the anti-inflammatory activity of intravenous IgG requires specific Fc glycans for activity. In particular, the anti-inflammatory activity of intravenous IgG is ascribed to a small population of IgGs in which the Asn297-linked complex N-glycans attached to each Fc CH2 domain include terminal α2,6-linked sialic acids. We used chemoenzymatic glycoengineering to prepare fully disialylated IgG Fc and solved its crystal structure. Comparison of the structures of asialylated Fc, sialylated Fc, and F241A Fc, a mutant that displays increased glycan sialylation, suggests that increased conformational flexibility of the CH2 domain is associated with the switch from pro-inflammatory to anti-inflammatory activity of the Fc.

  15. Biased immunoglobulin light chain gene usage in the shark1

    PubMed Central

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-01-01

    This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

  16. 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.

  17. Mechanisms of action of intravenous immunoglobulin in inflammatory muscle disease.

    PubMed

    Quick, Adam; Tandan, Rup

    2011-06-01

    Intravenous immunoglobulin (IVIG) is a unique immune-modulating therapy that has a wide range of effects on the immune system at multiple levels. This allows it to be used successfully in a variety of immune-mediated, systemic, and neurological disorders, including the inflammatory myopathies. It is likely that the specific action of IVIG varies depending on the underlying pathogenesis of a given disease. In dermatomyositis (DM), IVIG has been shown to diminish the activity of complement and deposition of membrane attack complex on capillaries and muscle fibers, the expression of adhesion molecules, and cytokine production. IVIG also appears to modify gene expression in the muscle of DM patients. The mechanism by which IVIG affects muscle in polymyositis and inclusion body myositis has not been well-studied. However, it may work via suppression of T-cell activation (including cytotoxic T cells) and migration into muscle tissue and alterations in cytokine production. IVIG generally yields the greatest therapeutic benefit in DM and is often of marginal utility in inclusion body myositis. It is generally considered as second-line or adjunctive therapy in the inflammatory myopathies.

  18. 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.

  19. 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

  20. Immunoglobulin λ Gene Rearrangement Can Precede κ Gene Rearrangement

    DOE PAGES

    Berg, Jörg; Mcdowell, Mindy; Jäck, Hans-Martin; ...

    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

  1. 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.

  2. Protein A affinity precipitation of human immunoglobulin G.

    PubMed

    Janoschek, Lars; Freiherr von Roman, Matthias; Berensmeier, Sonja

    2014-08-15

    The potential of protein A affinity precipitation as an alternative method for traditional antibody purification techniques was investigated. Recombinant produced protein A from Staphylococcus aureus (SpA) was covalently linked to the pH-responsive copolymer Eudragit(®) S-100 and used for purification of human immunoglobulin G (hIgG). The Eudragit-SpA conjugate had a static binding capacity of 93.9 ± 2.8 mg hIgG per g conjugate and a dissociation constant of 787 ± 67 nM at 7 ± 1°C. The antibody was adsorbed rapidly onto Eudragit-SpA and reached equilibrium within 5 min. An excess of hIgG binding sites, provided by the conjugate, as well as adjusted elution conditions resulted in an appropriate hIgG purification performance. In summary, Eudragit-SpA was successfully applied to capture hIgG from a protein mixture with 65% antibody yield in the elution step. Nearly 96% purity and a purification factor of 12.4 were achieved. The Eudragit-SpA conjugate showed a stable ligand density over several cycles, which enabled reusability for repeated precipitation of hIgG. According to this, pH induced affinity precipitation can be seen as a potential alternative for protein A chromatography in antibody purification processes.

  3. Immunoglobulin light chain isotypes in the teleost Trematomus bernacchii.

    PubMed

    Coscia, Maria Rosaria; Giacomelli, Stefano; De Santi, Concetta; Varriale, Sonia; Oreste, Umberto

    2008-06-01

    Three immunoglobulin light chain (IgL) isotypes TrbeL1, TrbeL2, and TrbeL3 were identified in the Antarctic teleost Trematomus bernacchii by immunoscreening a cDNA expression library, and using RT-PCR, and 5' RACE. One of them was distinguished in two subisotypes TrbeL1A and TrbeL1B. Real-time PCR experiments showed that the different isotypes were expressed in similar ratios in the various tissues analyzed. Interestingly, the expression level of TrbeL1A isotype was very high in all tissues. Molecular models of the CH1-CL domain pairings were built and minimized for the different isotypes. Several differences were identified in the superimposable structures mainly in the loops. In addition, the isotype-specific residues determined a different distribution of the charges on the external CL domain surface. Phylogenetic trees of 43 isotype representative sequences of CL domain from teleost species, built by different methods, indicated that all teleost light chain isotypes are distributed into three groups. Furthermore, the split of the group IgL1 into two subgroups, one of them carrying a micro-satellite DNA insertion, may have occurred in the Acanthopterygean ancestor.

  4. Inhibitory leukocyte immunoglobulin-like receptors in cancer development.

    PubMed

    Zhang, FeiFei; Zheng, JunKe; Kang, XunLei; Deng, Mi; Lu, ZhiGang; Kim, Jaehyup; Zhang, ChengCheng

    2015-12-01

    Inhibitory leukocyte immunoglobulin-like receptors (LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase (SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.

  5. Immunoglobulin G4-related ophthalmic disease presenting as uveitis.

    PubMed

    Prayson, Richard A

    2015-11-01

    This report documents a 47-year-old man who presented with back pain, uveitis and an elevated Westergren sedimentation rate. On biopsy, a paraspinal lesion showed a nonspecific chronic inflammatory cell infiltrate. The eye symptoms, after initially responding to immunosuppressive therapy, worsened and progressed to pain, resulting in an extirpation of the right eye. The histopathology of the excised eye showed an inflammatory pseudotumor marked by a lymphoplasmacytic infiltrate, areas of fibrosis, rare evidence of obliterative phlebitis and, focally, over 20 Immunoglobulin G4 (IgG4)-positive staining cells per high power microscopic field. IgG4-related ophthalmic disease is a relatively rare inflammatory lesion involving the eye and periorbital region. It is defined by a marked lymphoplasmacytic cell infiltrate, fibrosis obliterative phlebitis and increased IgG4 immunostaining (at least 10 cells per high power microscopic field in excised tissue). The entity is not unique to the eye, and has been described in other organs including the brain, endocrine organs, liver and kidney. The clinical presentation is often related to the location of the inflammatory infiltrates, and treatment involves the use of corticosteroids and other immunosuppressive agents. It is important to recognize IgG4-related ophthalmic disease because the condition appears to put patients at increased risk of developing lymphoma.

  6. 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.

  7. Immunoglobulins: 25 years of immunoinformatics and IMGT-ONTOLOGY.

    PubMed

    Lefranc, Marie-Paule

    2014-12-16

    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).

  8. Detection of specific immunoglobulin E in patients with toxoplasmosis.

    PubMed Central

    Pinon, J M; Toubas, D; Marx, C; Mougeot, G; Bonnin, A; Bonhomme, A; Villaume, M; Foudrinier, F; Lepan, H

    1990-01-01

    An immunocapture assay was developed to detect Toxoplasma gondii-specific immunoglobulin E (IgE) in sera from adults with acute acquired infection or reactivation and from babies with congenital toxoplasmosis. The components of this assay were monoclonal antibody to human IgE, samples from patients, and T. gondii tachyzoites treated with Formalin. When T. gondii-specific IgE antibodies were present, visually detectable agglutination occurred. Sera, umbilical cord blood, fetal blood, cerebrospinal fluid, and amniotic fluid were tested by this method. Specific IgE antibodies were detected in sera from 25 (86%) of 29 adults who developed specific IgG antibody during pregnancy or had specific IgA and IgM antibodies. Specific IgE was present early during infection, at the time that IgM antibodies were present, and slightly preceding the presence of specific IgA antibodies. In 23 patients tested serially, IgE antibodies never persisted for longer than 4 months. No nonspecific anti-T. gondii IgE was detected in sera from uninfected individuals. Maternal IgE antibodies did not cross the placenta. In sera of patients with congenital toxoplasmosis, specific IgE antibodies were found at birth, during the first year of life, and during immunologic recrudescence following discontinuation of pyrimethamine-sulfonamide therapy. The IgE immunocapture assay is simple to perform. It is especially useful for determining when T. gondii was acquired by recently infected pregnant women. PMID:2203811

  9. 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.

  10. Oligoclonal immunoglobulins and smooth muscle antibodies in arthritic joints.

    PubMed

    Mellbye, O J; Fyrand, O; Brath, H K; Olsen, E

    1980-04-01

    In twelve synovial fluid/serum pairs from patients with various types of seronegative polyarthritis, homogeneous gamma-bands by agarose gel electrophoresis were found in seven of the synovial fluids and in only one of the sera. In six of the fluids with gamma-bands, smooth muscle antibodies (SMA) were also present, usually in a titre identical to that in serum. In fluids with no gamma-bands, no SMA were detected. In forty synovial fluid/serum pairs from paitients with seropositive rheumatoid arthritis, no gamma-bands were detected in the synovial fluids, and SMA were present in only three pairs. Absorption and inhibition experiments did not give evidence that the SMA activity in seronegative polyarthritis was confined to the gamma-bands in the synovial fluids. The SMA activity in the fluids seemed to be directed against both actin and 'non-actin' muscular antigens. The association between locally produced oligoclonal immunoglobulins and possible locally produced SMA with differnet electrophoretic mobility suggests that in some of thes patients there is a local synovial production of oligoclonal antibodies with different specificities. Thus, even if the results may indicate a local virus infection in some arthritic joints, they may also be dur to an unspecific local stimulation of B cells or to a specific antigen stimulation combined with an unspecific co-activation of other antibody-producing cells.

  11. A double-strand break can trigger immunoglobulin gene conversion

    PubMed Central

    Bastianello, Giulia; Arakawa, Hiroshi

    2017-01-01

    All three B cell-specific activities of the immunoglobulin (Ig) gene re-modeling system—gene conversion, somatic hypermutation and class switch recombination—require activation-induced deaminase (AID). AID-induced DNA lesions must be further processed and dissected into different DNA recombination pathways. In order to characterize potential intermediates for Ig gene conversion, we inserted an I-SceI recognition site into the complementarity determining region 1 (CDR1) of the Ig light chain locus of the AID knockout DT40 cell line, and conditionally expressed I-SceI endonuclease. Here, we show that a double-strand break (DSB) in CDR1 is sufficient to trigger Ig gene conversion in the absence of AID. The pattern and pseudogene usage of DSB-induced gene conversion were comparable to those of AID-induced gene conversion; surprisingly, sometimes a single DSB induced multiple gene conversion events. These constitute direct evidence that a DSB in the V region can be an intermediate for gene conversion. The fate of the DNA lesion downstream of a DSB had more flexibility than that of AID, suggesting two alternative models: (i) DSBs during the physiological gene conversion are in the minority compared to single-strand breaks (SSBs), which are frequently generated following DNA deamination, or (ii) the physiological gene conversion is mediated by a tightly regulated DSB that is locally protected from non-homologous end joining (NHEJ) or other non-homologous DNA recombination machineries. PMID:27701075

  12. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease.

    PubMed

    Palm, Noah W; de Zoete, Marcel R; Cullen, Thomas W; Barry, Natasha A; Stefanowski, Jonathan; Hao, Liming; Degnan, Patrick H; Hu, Jianzhong; Peter, Inga; Zhang, Wei; Ruggiero, Elizabeth; Cho, Judy H; Goodman, Andrew L; Flavell, Richard A

    2014-08-28

    Specific members of the intestinal microbiota dramatically affect inflammatory bowel disease (IBD) in mice. In humans, however, identifying bacteria that preferentially affect disease susceptibility and severity remains a major challenge. Here, we used flow-cytometry-based bacterial cell sorting and 16S sequencing to characterize taxa-specific coating of the intestinal microbiota with immunoglobulin A (IgA-SEQ) and show that high IgA coating uniquely identifies colitogenic intestinal bacteria in a mouse model of microbiota-driven colitis. We then used IgA-SEQ and extensive anaerobic culturing of fecal bacteria from IBD patients to create personalized disease-associated gut microbiota culture collections with predefined levels of IgA coating. Using these collections, we found that intestinal bacteria selected on the basis of high coating with IgA conferred dramatic susceptibility to colitis in germ-free mice. Thus, our studies suggest that IgA coating identifies inflammatory commensals that preferentially drive intestinal disease. Targeted elimination of such bacteria may reduce, reverse, or even prevent disease development.

  13. Analysis of the structural integrity of YACs comprising human immunoglobulin genes in yeast and in embryonic stem cells

    SciTech Connect

    Mendez, M.J.; Abderrahim, H.; Noguchi, M.

    1995-03-20

    With the goal of creating a strain of mice capable of producing human antibodies, we are cloning and reconstructing the human immunoglobulin germline repertoire in yeast artificial chromosomes (YACs). We describe the identification of YACs containing variable and constant region sequences from the human heavy chain (IgH) and kappa light chain (IgK) loci and the characterization of their integrity in yeast and in mouse embryonic stem (ES) cells. The IgH locus-derived YAC contains five variable (V{sub H}) genes, the major diversity (D) gene cluster, the joining (J{sub H}) genes, the intronic enhancer (E{sub H}), and the constant region genes, mu (C{mu}) and delta (C{delta}). Two IgK locus-derived YACs each contain three variable (V{kappa}) genes, the joining (J{kappa}) region, the intronic enhancer (E{kappa}), the constant gene (C{kappa}), and the kappa deleting element (kde). The IgH YAC was unstable in yeast, generating a variety of deletion derivatives, whereas both IgK YACs were stable. YACs encoding heavy chain and kappa light chain, retrofitted with the mammalian selectable marker, hypoxanthine phosphoribosyltransferase (HPRT), were each introduced into HPRT-deficient mouse ES cells. Analysis of YAC integrity in ES cell lines revealed that the majority of DNA inserts were integrated in substantially intact form. 78 refs., 7 figs.

  14. 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.

  15. Characterization of cysteine-linked conjugation profiles of immunoglobulin G1 and immunoglobulin G2 antibody-drug conjugates.

    PubMed

    Wiggins, Brian; Liu-Shin, Lily; Yamaguchi, Hideto; Ratnaswamy, Gayathri

    2015-04-01

    Two US FDA-approved antibody-drug conjugates (ADCs; Kadcyla(®) and Adcetris(®) ) have accelerated clinical interest in the potential of targeted cancer therapeutics as the next generation of oncology drugs that are designed to increase efficacy while reducing overall toxicity. Thiol conjugates are produced by partial reduction of the interchain disulfides, followed by conjugation with a drug-linker, resulting in a heterogeneous mix of molecules that differ with respect to the site of conjugation and the number of drugs per antibody. ADCs that have been characterized in this class have an immunoglobulin G1 (IgG1) framework and there is little information available on IgG2 ADCs. As IgG1s and IgG2s differ in the number of disulfides and molecular conformations, each subclass could lead to unique combinations of possible conjugation sites. We conducted in-depth characterization of two ADCs, an IgG1 and an IgG2 conjugated to monomethyl auristatin E. The results demonstrate that the IgG1 monoclonal antibodies favor conjugation to the cysteines between the light and heavy chains, whereas IgG2s demonstrate preference for the hinge region cysteines. The drug-loading distribution and conjugation sites of ADCs have been reported to influence pharmacokinetics, toxicity, and clearance. Therefore, an understanding of the conjugation profiles is important for the selection and engineering of ADCs.

  16. 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.

  17. Estimation of serum and salivary immunoglobulin G and immunoglobulin A in oral pre-cancer: A study in oral submucous fibrosis and oral lichen planus

    PubMed Central

    Divya, V. C.; Sathasivasubramanian, S.

    2014-01-01

    Aim: Oral submucous fibrosis (OSMF) and oral lichen planus (OLP) are two frequently reported, potentially malignant disorders with multifactorial etiologies and ambiguous pathogenesis. An immunological pathogenesis has been hypothesized as a causative factor for both. The present study aims to evaluate the role of serum and salivary immunoglobulin G (IgG) and immunoglobulin A (IgA) in both these conditions, by their quantitative estimation. Materials and Methods: Saliva and serum samples were collected from 30 patients, clinically diagnosed and histopathologically confirmed with OSMF, 30 with OLP and 30 age and sex matched controls. The levels of IgG and IgA were estimated by nephelometry. Results: The mean values of serum IgG were marginally higher in both OSMF and OLP groups compared to the controls but this difference was not significant and the mean values of serum immunoglobulin A were marginally decreased in both the study groups compared to the controls but this difference was also not significant. Inconclusively low levels of salivary IgG and IgA were obtained in the three groups. Conclusion: The present study suggests an insignificant association of these immunoglobulins in the pathogenesis of both these diseases. PMID:24678204

  18. 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

  19. 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

  20. Detection of Impaired IgG Antibody Formation Facilitates the Decision on Early Immunoglobulin Replacement in Hypogammaglobulinemic Patients

    PubMed Central

    Wolf, Hermann M.; Thon, Vojtech; Litzman, Jiri; Eibl, Martha M.

    2015-01-01

    Hypogammaglobulinemia (serum IgG lower than 2 SD below the age-matched mean) and clinical symptoms such as increased susceptibility to infection, autoimmune manifestations, granulomatous disease, and unexplained polyclonal lymphoproliferation are considered to be diagnostic hallmarks in patients with common variable immunodeficiency (CVID), the most frequent clinically severe primary immunodeficiency syndrome. In the present study, we investigated patients with hypogammaglobulinemia and no clinical or immunological signs of defective cell-mediated immunity and differentiated two groups on the basis of their IgG antibody formation capacity against a variety of different antigens (bacterial toxins, polysaccharide antigens, viral antigens). Patients with hypogammaglobulinemia and intact antibody production (HIAP) displayed no or only mild susceptibility to infections, while CVID patients showed marked susceptibility to bacterial infections that normalized following initiation of IVIG or subcutaneous immunoglobulin replacement therapy. There was a substantial overlap in IgG serum levels between the asymptomatic HIAP group and the CVID patients examined before immunoglobulin treatment. HIAP patients showed normal levels of switched B-memory cells (CD19+CD27+IgD−), while both decreased and normal levels of switched B-memory cells could be found in CVID patients. IgG antibody response to a primary antigen, tick-borne encephalitis virus (TBEV), was defective in CVID patients, thus confirming their substantial defect in IgG antibody production. Defective IgG antibody production against multiple antigens could also be demonstrated in an adult patient with recurrent infections but normal IgG levels. To facilitate early treatment before recurrent infections may lead to organ damage, the antibody formation capacity should be examined in hypogammaglobulinemic patients and the decision to treat should be based on the finding of impaired IgG antibody production. PMID:25699049

  1. Levels of serum immunoglobulins in apparently healthy children and adults in Port Harcourt, Nigeria.

    PubMed

    Obiandu, C; Okerengwo, A A; Dapper, D V

    2013-06-30

    Serum levels of the immunoglobulins: IgG, IgA and IgM were determined by the single radial immunodiffusion technique of Mancini in a total of 122 apparently healthy subjects consisting of 43 children (20 males; 23 females) aged 5-12 years and 79 adults (39 males; 40 females) aged 18-65 years resident in Port Harcourt, southeastern Nigeria. The effects of age and sex on the serum levels of the various immunoglobulin types were also determined. The mean values and ranges for the various immunoglobulin types are presented for both children and adults. Although, female children were found to have significantly lower mean values of IgA compared to male children (p<0.05), there were no significant differences in the mean values of both IgG and IgM between male and female children involved in the present study (p>0.05). However, female adults had significantly higher mean values of IgG and significantly lower mean values of IgA compared to male adults (p<0.05); suggesting a significant gender difference in the value of both IgG and IgA amongst adult subjects. No significant differences were observed in the mean values of any of the various types of immunoglobulin between adults and children. The present study reports mean values of the various types of immunoglobulin in apparently healthy children and adults resident in Port Harcourt, southeastern Nigeria. Significant gender differences were observed for some of the immunoglobulin types only amongst adults. Our results suggest that these gender differences amongst adults were apparently a gradual build-up from childhood. The results also confirm suggestions that levels of some immunoglobulin types seen amongst African adults may have possibly been attained during childhood. Our study could be of value since previous reports in this regard have been relatively scanty especially in this part of Nigeria.

  2. 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

  3. Switch from intravenous to subcutaneous immunoglobulin in CIDP and MMN: improved tolerability and patient satisfaction

    PubMed Central

    Marreno, Fabrizio

    2015-01-01

    Objectives: To assess clinical outcomes and patient satisfaction in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or multifocal motor neuropathy (MMN) who were switched from intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin (SCIG). Methods: Eight consecutive patients, four with MMN and four with CIDP, already on long-term, hospital-based IVIG were switched to home-based SCIG. These patients were selected on the basis of their requirement for relatively low treatment doses, problems experienced with IVIG, and their willingness to switch to SCIG. Results: After a mean 33 [standard deviation (SD) 19] months receiving SCIG, 7 patients remained neurologically stable and 6 remained on a similar mean weekly immunoglobulin dose relative to their original intravenous dose. A good outcome was reported by 7 of the 8 patients: there were improvements in nausea and headache (n = 4), need to travel to hospital (n = 4), venous access problems (n = 3), immunoglobulin-induced neutropenia (n = 3), treatment wearing-off fluctuations (n = 2), IVIG-induced allergy requiring antihistamine/hydrocortisone (n = 1) and time taken off work (n = 1). The eighth patient required increasing doses of immunoglobulin to maintain strength but still wanted to continue SCIG. Seven patients completed a questionnaire: there was a very high overall satisfaction level with immunoglobulin treatment [mean 96 (SD 5), visual analogue scale (VAS) where 0 = very unsatisfied, 100 = very satisfied]; and very strong preference for subcutaneous over intravenous immunoglobulin (VAS mean 93 [SD 12] where 0 = prefer IVIG, 100 = prefer SCIG). Conclusions: In seven of the eight patients, SCIG gave improved tolerability and patient satisfaction with similar efficacy compared with IVIG. PMID:25584070

  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. Validation of Brix refractometer to estimate colostrum immunoglobulin G content and composition in the sow.

    PubMed

    Hasan, S M K; Junnikkala, S; Valros, A; Peltoniemi, O; Oliviero, C

    2016-10-01

    Colostrum is an essential source of immunoglobulin G (IgG) for neonate piglets. However, colostrum IgG content and nutritional composition can vary considerably among sows due to age, parity, feeding regime and immunological background. Currently, there is no practical way to obtain information about colostrum IgG concentration at herd level. We evaluated sows' colostrum IgG content on-farm using a Brix refractometer and its performance was compared with that of an IgG ELISA. In addition, nutritional compositions of the colostrum samples were analyzed using Fourier transform IR spectroscopy. Colostrum samples (5 to 6 ml) (n=153) were obtained within 0 to 3 h of farrowing. However, to obtain a 24 h IgG profile for 11 sows, colostrum samples were collected at 0, 2, 4, 6, 8, 10, 16 and 24 h after farrowing. A 0.3 ml of freshly drawn colostrum sample was used for the on-farm measurement of Brix percentages using a digital refractometer shortly after collection. The remaining fractions of the samples were frozen and submitted to laboratory analysis for total IgG, using a commercially available pig IgG ELISA kit. For nutritional composition analysis, a 35 ml colostrum sample (n=34) was obtained immediately after birth of first piglet from the first three pairs of frontal teats. Colostrum concentrations of IgG averaged 52.03±30.70 mg/ml (mean±SEM) at 0 to 3 h after farrowing. Concentration of IgG decreased on average by 50% during the 1st day of lactation (P30%. Colostrum IgG concentration is highly variable among sows, Brix measurement of a sows' fresh colostrum is an inexpensive, rapid and satisfactorily accurate method of estimating IgG concentration, providing indication of differentiation between good and poor IgG content of colostrum.

  6. Increased immunoglobulin G, but not M, binding to endogenous retroviral antigens in HIV-1 infected persons.

    PubMed

    Lawoko, A; Johansson, B; Rabinayaran, D; Pipkorn, R; Blomberg, J

    2000-12-01

    The modes of interaction between products of human endogenous retroviral (HERV) sequences and the immune system are largely unknown. In HIV infected persons, an exogenous retrovirus adds further complexity to the situation. Therefore, 14 synthetic peptides with sequences derived from conserved regions of various endogenous retroviruses (ERVs) and from related exogenous retroviruses were used to search for IgG and IgM antibodies that bind to such antigens in 15 HIV-1 seropositive and 17 seronegative immunosuppressed patients. IgG binding to three peptides, namely, the C-terminal half of murine leukemia virus (MLV) capsid protein, the conserved portion of HERV-H transmembrane protein, and the Pol region of human mouse mammary tumor virus (MMTV)-like (HML3) sequence, was observed in both groups. Binding was, however, more frequent and more firm in HIV-1 positive samples (P<0.0001, Wilcoxon rank sum test). IgM binding to the same peptides showed no significant differentiation between the two groups of patients. Binding to both immunoglobulin isotypes was sometimes variable over time in both groups. No correlation of either IgG or IgM peptide binding with progression to AIDS in HIV-1 infected individuals was observed. Inhibition studies using analogous endogenous and exogenous retroviral peptides, including HIV-1, demonstrated specificity of the IgG antibodies for a narrow range of MLV- and MMTV-like retroviral antigens, and excluded cross-reactivity of antibodies to HIV-1 as a cause of these observations. Thus, unlike IgG, IgM binding to retroviral antigens was ubiquitous. It is suggested that anti-HERV IgM belong to a class of natural antibodies and might serve as primers in the mediation of humoral immune responses to more or less related exogenous retroviruses. Increased IgG binding in HIV-1 infected individuals could result from such priming, or reflect higher HERV antigen expression.

  7. Polymorphism in anti-phosphocholine antibodies reflecting evolution of immunoglobulin families

    PubMed Central

    1983-01-01

    Complete variable (V) region amino acid sequences were determined for four heavy (H) and one light (L) chain from C57BL phosphocholine (PC)- binding monoclonal antibodies. Additional NH2-terminal sequences were obtained from H and L chains of C57BL and CBA/J origin. When these V regions were compared with previously reported anti-PC sequences, a number of observations could be made regarding the function and evolution of L and H chain segments used in these antibodies. (a) L and H chain V segments are remarkably conserved in these inbred strains, although there has been an accumulation of point mutations identifying apparently allelic forms of VK and VH. (b) Mice of each genotype use the same three VK segments in combination with a single VH segment to produce most anti-PC antibodies. An exception has been noted that indicates the occasional use of a second VH gene segment. (c) Multiple, different DH regions are used by mice of each strain, which suggests that the DH segment sequence plays no critical role in either antigen binding or VH-VL pairing. Furthermore, the DH segments and their corresponding gene families appear to be highly conserved in the inbred strains studied. (d) Most PC-binding antibodies use the JH1 joining segment. All JH1 sequences from C57BL mice differ from the BALB/c JH1 at position 105, which identifies allelic forms of the JH1 region. These studies are a first assessment of the nature of mutational events associated with the evolution of specific multigene immunoglobulin families and indicate that homologous VH, DH, JH, VK, and JK genes are similarly assembled and expressed in PC antibodies from three diverse genotypes. PMID:6401319

  8. Immunoglobulin and T Cell Receptor Genes: IMGT(®) and the Birth and Rise of Immunoinformatics.

    PubMed

    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).

  9. The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins

    PubMed Central

    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

    2014-01-01

    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. PMID:24830426

  10. 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

    2014-06-03

    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.

  11. cDNA cloning of the immunoglobulin heavy chain genes in banded houndshark Triakis scyllium.

    PubMed

    Honda, Yuka; Kondo, Hidehiro; Caipang, Christopher Marlowe A; Hirono, Ikuo; Aoki, Takashi

    2010-11-01

    In this study, cDNAs encoding the secreted forms of the immunoglobulin (Ig) heavy chains of IgM, IgNAR, and IgW were cloned from the banded houndshark Triakis scyllium. Two clones for the IgM heavy chains encoded 569 and 570 amino acids, whose conserved (C) region showed 47-70% amino acid identities to those reported in other cartilaginous fish. Four clones for the IgNAR encoded 673-670 amino acids with conserved Ig-superfamily domains. The IgNAR C region showed 56-69% amino acid identities to those so far reported. High-throughput sequencing revealed that in most of the IgNAR sequences, the two variable regions (CDR1 and CDR3) each possess a cysteine residue. Three types of IgW were identified; one contained Ig-superfamily domains that are in other cartilaginous fish, one lacks the 3rd domain in the constant region, and one lacks the 3rd to 5th domains. Despite these differences, the IgW isoforms clustered with IgWs of other cartilaginous fishes and the C regions showed 47-89% amino acid identities. mRNAs for IgM and IgNAR were detected in various tissues, while IgW mRNA was mainly detected in pancreas. The banded hounded shark also has IgM, IgW and IgNAR as well as the other cartilaginous fish with unique IgW isoform.

  12. Excretion of Human Immunodeficiency Virus Type 1 through Polarized Epithelium by Immunoglobulin A▿

    PubMed Central

    Wright, Alison; Lamm, Michael E.; Huang, Yung T.

    2008-01-01

    Human immunodeficiency virus (HIV) is transmitted primarily sexually across mucosal surfaces. After infection, HIV propagates initially in the lamina propria below the polarized epithelium and causes extensive destruction of mucosal T cells. Immunoglobulin A (IgA) antibodies, produced in the lamina propria and then transcytosed across the mucosal epithelium into the lumen, can be the first line of immune defense against HIV. Here, we used IgA monoclonal antibodies against HIV envelope proteins to investigate the abilities of polarized primate and human epithelial cells to excrete HIV virions from the basolateral to the apical surface via polymeric Ig receptor (pIgR)-mediated binding and the internalization of HIV-IgA immune complexes. African green monkey kidney cells expressing pIgR demonstrated HIV excretion that was dependent on the IgA concentration and the exposure time. Matched IgG antibodies with the same variable regions as the IgA antibodies and IgA antibodies to non-HIV antigens had no HIV excretory function. A mixture of two IgA anti-bodies against gp120 and gp41 showed a synergistic increase in the level of HIV excreted. The capacity for HIV excretion correlated with the ability of IgA antibodies to bind HIV and of the resulting immune complexes to bind pIgR. Consistent with the epithelial transcytosis of HIV-IgA immune complexes, the colocalization of HIV proteins and HIV-specific IgA was detected intracellularly by confocal microscopy. Our results suggest the potential of IgA antibodies to excrete HIV from mucosal lamina propria, thereby decreasing the viral burden, access to susceptible cells, and the chronic activation of the immune system. PMID:18829757

  13. 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

  14. Scaffolds for oriented and close-packed immobilization of immunoglobulins.

    PubMed

    Iijima, Masumi; Kuroda, Shun'ichi

    2017-03-15

    Immunosensing is a widely used technique that detects the interactions between antibodies and antigens such as biochemical markers, pathogens, allergens, and tumor-associated antigens. Since target antigens are often of high molecular mass and their binding affinities are sometimes weak, the spatial arrangement of immunoglobulin Gs (IgGs) on immunosensing probes should be optimized by presenting them in as close-packed a manner as possible and reducing steric hindrance around the antigen-binding Fv regions. Both clustering and oriented immobilization of IgGs on immunosensing probes are thus important for enhancing the sensitivity and antigen-binding capacity of probes. Intact IgGs, IgG-derived fragments, or IgG-compatible fragments have previously been clustered onto solid phases with a variety of scaffold chemistries (e.g., crosslinkers, polymers, self-assembled monolayers, protein A/G, avidin, DNA) to improve immunosensing probes, none of these strategies has yet accomplished both clustering and oriented immobilization of IgGs. Recently, we developed an ~30-nm bio-nanocapsule (ZZ-BNC), consisting of transmembrane ZZ-L protein deploying a tandem form of the IgG Fc-binding Z domain derived from Staphylococcus aureus protein A on its outer surface that functioned as a scaffold for the clustering and oriented immobilization of IgGs and Fc-fused biosensing molecules. In this review, we present an overview of conventional techniques for IgG immobilization and describe the molecular basis of the ZZ-BNC-based technology, discussing the potential and versatility of this technology not only in immunosensors but also in other types of biosensors.

  15. Supercritical fluid precipitation of recombinant human immunoglobulin from aqueous solutions.

    PubMed

    Nesta, D P; Elliott, J S; Warr, J P

    2000-02-20

    Supercritical carbon dioxide was used as an antisolvent for producing recombinant human immunoglobulin G (rIgG) particulate powders. Liquid carbon dioxide (CO(2)) was premixed with ethanol to create a single-phase, modified supercritical fluid (SCF). The modified SCF was then vigorously mixed with a pharmaceutically acceptable, aqueous formulation of rIgG, and the mixture was immediately atomized into a pressurized vessel where rapid expansion of the modified SCF extracted the aqueous phase, resulting in precipitation of the protein powder. The process was reproducible, and resulting powder products were characterized by their aqueous solubilities, and the spectroscopic profile, molecular integrity, and antigen binding activity of the individual soluble fractions. Molecular integrity was assessed via size-exclusion high-performance liquid chromatography (SEC), whereas antigen binding activity was determined using an enzyme-linked immunosorbent assay (ELISA). Attempts to characterize particle size and morphology were confounded due to the extremely deliquescent nature of the powders, causing them to absorb moisture rapidly and become gummy. Operational conditions were optimized to a point which yielded powders that were completely soluble, and had ultraviolet (UV) spectroscopic and SEC profiles indistinguishable from those of the reference standard starting solution from which the powders were derived. Antigen binding activities of the powders, however, were

  16. SCM, the M Protein of Streptococcus canis Binds Immunoglobulin G

    PubMed Central

    Bergmann, Simone; Eichhorn, Inga; Kohler, Thomas P.; Hammerschmidt, Sven; Goldmann, Oliver; Rohde, Manfred; Fulde, Marcus

    2017-01-01

    The M protein of Streptococcus canis (SCM) is a virulence factor and serves as a surface-associated receptor with a particular affinity for mini-plasminogen, a cleavage product of the broad-spectrum serine protease plasmin. Here, we report that SCM has an additional high-affinity immunoglobulin G (IgG) binding activity. The ability of a particular S. canis isolate to bind to IgG significantly correlates with a scm-positive phenotype, suggesting a dominant role of SCM as an IgG receptor. Subsequent heterologous expression of SCM in non-IgG binding S. gordonii and Western Blot analysis with purified recombinant SCM proteins confirmed its IgG receptor function. As expected for a zoonotic agent, the SCM-IgG interaction is species-unspecific, with a particular affinity of SCM for IgGs derived from human, cats, dogs, horses, mice, and rabbits, but not from cows and goats. Similar to other streptococcal IgG-binding proteins, the interaction between SCM and IgG occurs via the conserved Fc domain and is, therefore, non-opsonic. Interestingly, the interaction between SCM and IgG-Fc on the bacterial surface specifically prevents opsonization by C1q, which might constitute another anti-phagocytic mechanism of SCM. Extensive binding analyses with a variety of different truncated SCM fragments defined a region of 52 amino acids located in the central part of the mature SCM protein which is important for IgG binding. This binding region is highly conserved among SCM proteins derived from different S. canis isolates but differs significantly from IgG-Fc receptors of S. pyogenes and S. dysgalactiae sub. equisimilis, respectively. In summary, we present an additional role of SCM in the pathogen-host interaction of S. canis. The detailed analysis of the SCM-IgG interaction should contribute to a better understanding of the complex roles of M proteins in streptococcal pathogenesis.

  17. Are immunoglobulin concentrations associated with the body composition of adolescents?

    PubMed

    Zúñiga-Torres, María G; Martínez-Carrillo, Beatriz E; Pardo-Morales, Rosa V; Wärnberg, Julia; Marcos, Ascensión; Benítez-Arciniega, Alejandra D; Valdés-Ramos, Roxana

    2009-11-01

    The aim of this study was to analyze the association between serum concentrations of immunoglobulins (Ig) A, G, and M and body composition of adolescents from Mexico. Informed consent was obtained from parents and assent was obtained from the adolescents for the evaluation of 125 adolescents from the Capital city of Toluca and the adjacent semiurban county of Lerma de Villada. Height, weight, waist, and hip circumference were measured by trained personnel. Body mass index and waist:hip ratio were calculated from these measurements, whereas body fat (BF) was calculated from tricipital and subscapular skinfolds and measured by bioelectrical impedance. Serum concentrations of Ig were determined by nephelometry. Data were analyzed by independent samples t test and Pearson correlations. Subjects were mainly females (71.2%), with a mean age of 16.8 years (+/-0.8). No differences were reported in all indicators by weight or BF between gender. Female participants had higher Ig concentrations than males (IgG t = 2.24, p = 0.027; IgA t = 2.05, p = 0.043; IgM t = 4.49, p < 0.001). Positive correlations were reported for IgA and IgM with tricipital skinfold (r = 0.192, p = 0.041; and r = 0.221, p = 0.018, respectively) and for total BF by bioimpedance (r = 0.243, p = 0.009). Ig concentrations do not seem to be affected by overweight, obesity, or excessive or central BF in adolescents.

  18. Infantile immunoglobulin A nephropathy showing features of membranoproliferative glomerulonephritis.

    PubMed

    Kurosu, Akira; Oka, Noriko; Hamaguchi, Takeshi; Yoshikawa, Norishige; Joh, Kensuke

    2012-01-01

    Immunoglobulin A nephropathy (IgAN) showing predominant IgA and complement 3 (C3) deposition on the mesangium is an immune complex-mediated glomerulonephritis. This renal disease is the most common primary glomerular disease worldwide. However, infantile onset of IgAN is rare. In the present patient, urinary protein and occult blood were detected in a girl aged 1 year and 8 months on urinalysis at a nursery school. Despite being young, a kidney biopsy was performed for diagnosis and the correct choice of therapy. Glomerular mesangial cell proliferation and a double contour of the glomerular basement membrane (GBM) resembling a railroad track were noted on light microscopy. Therefore, the patient was diagnosed morphologically with membranoproliferative glomerulonephritis (MPGN), because mesangial hypercellularity and thickening of the GBM were identified. However, on immunofluorescent staining, the deposition of immune complexes mainly consisting of IgA, IgG, and C3 was noted in the mesangial region and glomerular capillary loops. On electron microscopy, electron-dense deposits were recognized in the subendothelial and paramesangial regions associated with mesangial cell interposition into the subendothelial space. Autoimmune diseases and infection-associated secondary glomerulonephritis were clinically excluded, because there were no relevant signs or symptoms. Steroid treatment was initiated and findings of urinalysis were normalized within 8 months. This patient was finally diagnosed with IgA nephropathy showing the features of MPGN. The present patient was the youngest among reported cases of IgA nephropathy, suggesting that early onset of IgAN is associated with an MPGN-like lesion. The present report provides information for pathogenesis of IgA nephropathy.

  19. Differential Diagnosis of Immunoglobulin G4-associated Cholangitis From Cholangiocarcinoma

    PubMed Central

    Du, Shunda; Liu, Gang; Cheng, Xinqi; Li, Yue; Wang, Qian; Li, Ji; Lu, Xin; Zheng, Yongchang; Xu, Haifeng; Chi, Tianyi; Zhao, Haitao; Xu, Yiyao; Sang, Xinting; Zhong, Shouxian

    2016-01-01

    Background and Aim: Immunoglobulin G4-associated cholangitis (IAC) shares many similar symptoms with cholangiocarcinoma (CCA). However, the treatment and the prognosis are substantially different. This study aimed to identify the important markers for the differential diagnosis of these 2 diseases. Methods: Thirty IAC patients and 275 CCA patients were reviewed retrospectively for their clinical symptoms, serological tests, and imaging characteristics. Posttreatment responses were also studied. Results: IgG4 had 100% specificity for IAC at a cutoff of 6 times the upper normal limit. IAC patients had a significantly higher incidence of weight loss (P=0.025) and a higher level of weight loss (P=0.008) than CCA patients. The positive rates of biological markers CA199, CA242, and CEA in CCA and IAC were 81.5% versus 42.9%, 45.5% versus 4.5%, and 29.2% versus 7.1%, respectively. Levels of these tumor markers in CCA were significantly higher than in IAC (P<0.05). The thickened wall [17/18 (94.4%) vs. 3/10 (30%), P=0.001] and the occupying lesion on the bile duct [1/18 (5.6%) vs. 8/10 (80%), P<0.001] were found to be significantly different in IAC and CCA, respectively, by endoscopic ultrasonography. Autoimmune pancreatitis was the most frequently observed comorbidity of IAC (25/30). All IAC patients respond positively to steroid treatment. Conclusions: Increased tumor markers, 6-fold higher levels of serum IgG4, and other organs’ involvement could be the reference factors for a differential diagnosis of IAC and CCA. Endoscopic ultrasonography might be an effective imaging tool for diagnosis, although clinical signs and symptoms of IAC and CCA are similar. Experimental steroid treatment can be useful in the diagnosis for certain difficult cases. PMID:26974756

  20. 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

  1. Allergen-specific immunoglobulin E and allergic rhinitis severity

    PubMed Central

    Corsico, Angelo G.; De Amici, Mara; Ronzoni, Vanessa; Giunta, Vania; Mennitti, Maria Chiara; Viscardi, Arianna; Marseglia, Gian Luigi

    2017-01-01

    Background: Allergic rhinitis (AR) is a common disorder. The diagnosis is based on the concordance between allergy sensitization and history. Serum allergen specific immunoglobulin E (sIgE) assessment allows characterization of the relevant sensitizing allergens. Presently, Allergic Rhinitis and its Impact on Asthma (ARIA) classification subdivides AR based on symptoms severity and duration. However, the relationship between sIgE levels and symptom severity is still a matter of debate. Objective: Therefore, this study aimed at relating sIgE levels with symptom severity assessed by ARIA classification in a group of patients with AR. Methods: We enrolled 217 patients with AR (123 women; median age, 39.5 years). The sIgE levels (expressed in kUA/L) to house-dust mite were detected by the fluorescence enzyme immunoassay in peripheral blood samples. The IgE calibrators were traceable to the second international reference preparation 75/502 of human serum IgE from the World Health Organization. Symptom severity was assessed by ARIA classification. Results: We found a significant difference in sIgE levels in patients with mild intermittent versus mild persistent symptoms (p < 0.05), mild intermittent versus moderate-to-severe persistent symptoms (p < 0.001), moderate-to-severe intermittent versus moderate-to-severe persistent symptoms (p < 0.01), and mild persistent versus moderate-to-severe persistent symptoms (p < 0.05). Conclusion: Analysis of these findings indicated that the sIgE level to house-dust mite might be a reliable biomarker for symptom severity in patients with AR. This outcome might be clinically relevant, particularly in candidates for immunotherapy. PMID:28381320

  2. 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.

  3. Immunoglobulin D Multiple Myeloma With Rapidly Progressing Renal Failure

    PubMed Central

    Modi, Jwalant; Kamal, Jeanne; Eter, Ahmad; El-Sayegh, Suzanne; El-Charabaty, Elie

    2015-01-01

    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

  4. 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.

  5. IGG Subclass and Isotype Specific Immunoglobulin Responses to LASSA fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunication

    DTIC Science & Technology

    1989-03-01

    DAIC FLL COpy AD-A218 815 A_ ARMY PROJECT ORDER NO: 88PP8804 TITLE: IGG SUBCLASS & ISOTYPE SPECIFIC IMMUNOGLOBULIN RESPONSES TO LASSA FEVER...TITLE (include Security Classification) IGG SUBCLASS & ISOTYPE SPECIFIC IMMUNOGLOBULIN RESPONSES TO LASSA FEVER & VENEZUELAN EQUINE ENCEPHALOMYELITIS...Immunoglobulin; IgG Sub- 06 01 classes; Lassa Fever; VEE; PO; Togavirus; IgG; IgA; IgM; 06 13 Arenavirus; Hemmorhagic Fever: BD; RA I 19, ABSTRACT

  6. 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

  7. Exclusion of polymeric immunoglobulins and selective immunoglobulin Y transport that recognizes its Fc region in avian ovarian follicles.

    PubMed

    Kitaguchi, Kohji; Osada, Kenichi; Horio, Fumihiko; Murai, Atsushi

    2008-02-15

    In avian species, blood immunoglobulin (Ig) Y, the equivalent to mammalian IgG, is selectively incorporated into ovarian follicles, but other classes, IgA and IgM, are much less abundant in the follicles. Several mammalian Igs, including IgG and IgA, are also incorporated into ovarian follicles when administered to birds. To clarify the Ig structure required for incorporation into ovarian follicles, Ig uptakes were determined after the intravenous injection of chicken and human Igs. Three chicken Igs (cIgY, cIgA and cIgM) and two human IgAs (monomeric hIgA and polymeric hIgA) were labeled with digoxigenin, and their uptakes into quail (Coturnix japonica) egg yolks were determined by ELISA and SDS-PAGE. The uptake of cIgY was the highest among the three cIgs (22% of injected cIgY was recovered from egg yolks). Chicken IgA was efficiently incorporated into egg yolk when it formed a monomeric state. Pentameric IgM was untransportable into egg yolk. We also found that the uptake of monomeric hIgA was much more efficient than that of polymeric hIgA. These results suggest that the retention of the monomeric form contributes to the efficient transport of Igs into ovarian follicles. On the other hand, Ig uptakes among monomeric Igs nevertheless differed; for example, a time-course analysis showed that the rate of monomeric cIgY uptake was approximately eight times faster than that of monomeric hIgA. The injection of cIgY fragments Fc, Fab and F(ab')(2) resulted in the largest uptake of Fc fragment, with the same level as that of cIgY. These results suggest the presence of a selective IgY transport system that recognizes its Fc region in avian ovarian follicles.

  8. Specific absorption of human serum albumin, immunoglobulin A, and immunoglobulin G with selected strains of group A and G streptococci.

    PubMed Central

    Kronvall, G; Simmons, A; Myhre, E B; Jonsson, S

    1979-01-01

    Five gram-positive bacterial strains were selected for absorption studies of human serum samples. Strain AR1 (group A, M-type 1) and G148 (group G), with strong immunoglobulin G (IgG) binding capacities, and strain AW43 (group A, M-type 60), binding both IgA1 and IgA2, were compared with Staphylococcus aureus Cowan I and with Staphylococcus epidermidis L603. Both AR1 and G148 were capable of completely absorbing out serum IgG. In contrast, S. aureus Cowan I left a fraction unabsorbed, as expected from its known lack of IgG3 binding. Strain AW43 absorbed out all serum IgA, using a 10-microliter bacterial pellet for 20 microliter of serum. Serum IgM levels were slightly reduced by S. aureus Cowan I absorption. On the basis of the experiments, a bacterial mixture was designed consisting of S. aureus Cowan I and group A streptococcus strains AR1 and AW43, with absorption characteristics suitable for use in discriminating between early IgM and late IgG and IgA immune responses in routine serological work. A new type of bacteria-mammalian protein binding was discovered. Human serum albumin was completely absorbed out by strain G148 and to a lesser extent by strain AR1 and AW43. S. aureus Cowan I and S. epidermidis were negative. The binding capacity of G148 for albumin equalled that of Cowan I for IgG. The binding pattern of albumin to the strains was different from those of IgG, IgA, IgM, fibrinogen, haptoglobin, or aggregated beta 2-microglobulin and therefore seems to represent another type of bacterial-mammalian interaction with a specific albumin receptor on the surface of streptococci. Images PMID:383609

  9. Monoclonal antibodies recognising serum immunoglobulins and surface immunoglobulin-positive cells of puffer fish, torafugu (Takifugu rubripes).

    PubMed

    Miyadai, Toshiaki; Ootani, Maki; Tahara, Daisuke; Aoki, Masatoshi; Saitoh, Kenjiro

    2004-09-01

    Immunoglobulin of the torafugu, Takifugu rubripes, was purified by a combination of precipitation by low ionic strength dialysis and gel filtration. The Ig was used to immunise mice for the production of monoclonal antibody (MAb). Supernatants of hybridoma cultures were screened by enzyme-linked immunosorbent assay using purified-torafugu Ig-coated plates, and two stable hybridomas producing MAbs against torafugu Ig were obtained. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis under reducing conditions and Western blotting indicated that one MAb (16F3) was specific for the deglycosylated heavy chain of torafugu, and the other MAb (4H5) did not bind to the reduced Ig, suggesting that 4H5 recognised the higher-order structure of Ig. Under non-reduced conditions, both MAbs recognised mainly a 750 kDa band and also minor bands of 672, 410 and 205 kDa. MAb 16F3- and 4H5-primed magnetic beads (Dynabeads) adsorbed 84.9+/-3.3% and 63.6+/-4.4% of the torafugu Ig, respectively. The Ig adsorbed by MAb 16F3-primed Dynabeads was reactive to 4H5 on immunoblotting, and vice versa, indicating that the epitopes for both MAbs are held on the same Ig molecule. Both of these MAbs cross-reacted extensively with the Ig of other Takifugu species, but not with other genus. The MAbs were used to identify surface Ig-positive lymphocytes in the spleen, pronephros, peripheral blood and thymocytes of torafugu by flow cytometry. Flow cytometric analysis of the cells in the lymphocyte-enriched fraction revealed that 50.2+/-6.9% in the PBL, 11.8+/-1.7% in the mesonephros, 13.3+/-2.1% in the pronephros, 42.5+/-4.3% in the spleen and 3.2+/-0.6% in thymus were reactive to 4H5 or 16F3.

  10. The role of immunoglobulin for the treatment of Clostridium difficile infection: a systematic review.

    PubMed

    O'Horo, John; Safdar, Nasia

    2009-11-01

    Clostridium difficile is the most common infectious cause of nosocomial healthcare-associated diarrhea. The increasing prevalence of C difficile, spread in the community, virulence and frequent relapse has created an urgent need to identify new effective treatments for C. difficile infection. Among these, intravenous immunoglobulin (IVIG) is used for cases of severe C. difficile infection. We undertook a systematic review to examine the published literature pertaining to the use of immunoglobulin for C. difficile infection. Four retrospective studies and five case reports that addressed the use of IVIG for the treatment of C. difficile infection were identified. One study on the use of oral immunoglobulin was identified. Although overall there appear to be benefits to using IVIG in recurrent severe disease, the small sample sizes and lack of control groups in three of the four studies do not allow recommendations to be made regarding the use of immunoglobulin in C. difficile infection. Further research is urgently needed to clarify the role of immunoglobulin--intravenous or oral--for the treatment of C. difficile infection.

  11. 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.

  12. 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.

  13. 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.

  14. A Preliminary Analysis of the Immunoglobulin Genes in the African Elephant (Loxodonta africana)

    PubMed Central

    Guo, Yongchen; Bao, Yonghua; Wang, Hui; Hu, Xiaoxiang; Zhao, Zhihui; Li, Ning; Zhao, Yaofeng

    2011-01-01

    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 VH gene segments, 87 DH gene segments (the largest number in mammals examined so far), six JH 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 Vκ gene segments, three 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 68 includes 15 Vλ gene segments, all with the same transcriptional polarity as the downstream Jλ-Cλ 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. PMID:21364892

  15. 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.

  16. Homologous recombination can restore normal immunoglobulin production in a mutant hybridoma cell line.

    PubMed Central

    Baker, M D; Pennell, N; Bosnoyan, L; Shulman, M J

    1988-01-01

    We report here the occurrence of homologous recombination between transferred and chromosomal immunoglobulin genes. Specifically, we have corrected a chromosomal immunoglobulin gene mutation by transferring pSV2neo vectors encoding the constant region of the immunoglobulin mu heavy chain to mutant hybridoma cells that bear a 2-base-pair deletion in the third constant region exon of their chromosomal mu gene. After DNA transfer, we detected G418-resistant transformants that produce normal IgM. Analysis of the DNA structure of the mu gene in these transformants indicates that in four of five cases the mu gene has been restored as a result of the integration of a single copy of the transfer vector by a reciprocal homologous recombination event; the fifth case seems to have resulted from gene conversion or double crossover. These results suggest that this technology might be adapted for mapping immunoglobulin gene mutations by marker rescue and for more convenient engineering of specifically altered immunoglobulin. Images PMID:2842771

  17. Rapid determination of immunoglobulin G concentration in cold ethanol precipitation process of raw plasma with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhang, Hui; Liu, Aihua; Zang, Hengchang; Li, Hu; Jiang, Wei; Li, Lian; Wang, Jinfeng

    2013-12-01

    Near-infrared spectroscopy (NIRS) is known to be a powerful analytical tool in process monitoring. The feasibility of NIRS was investigated for determination of immunoglobulin G (IgG) in raw plasma cold ethanol precipitation process. Partial least squares (PLS) was used to develop regression model for 63 samples between spectra and reference data measured with a UV spectrophotometer. Three different variable selection methods, including correlation coefficient method, interval partial least squares (iPLS) and successive projection algorithm (SPA), were performed and compared with models based on all the variables. The values of Rc and root mean square error of cross validation (RMSECV) produced by the best model for the calibration set were 0.9599 and 0.6135 g/L, respectively. While for the validation set, the values of Rp and root mean square error of prediction (RMSEP) were 0.9577 and 0.4913 g/L, respectively. The results of this paper demonstrated that NIRS could be a feasible alternative approach for rapid determination of IgG in the cold ethanol precipitation process and can be used as a PAT tool in the future.

  18. 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.

  19. Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution

    PubMed Central

    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

  20. Plasma haptoglobin and immunoglobulins as diagnostic indicators of deoxynivalenol intoxication

    PubMed Central

    Kim, Eun-Joo; Cho, Joon-Hyoung; Ku, Hyun-Ok; Pyo, Hyun-Mi; Kang, Hwan-Goo; Choi, Kyoung-Ho

    2008-01-01

    This study aimed to discover potential biomarkers for dioxynivalenol (DON) intoxication. B6C3F1 male mice were orally exposed to 0.83, 2.5 and 7.5 mg/kg body weight (bw) DON for 8 days and the differential protein expressions in their blood plasma were determined by SELDI - Time-of-Flight/Mass Spectrometry (TOF/MS) and the immunoglobulins (Igs) G, A, M and E in the serum were investigated. 11.7 kDa protein was significantly highly expressed according to DON administration and this protein was purified by employing a methyl ceramic HyperD F column with using optimization buffer for adsorption and desorption. The purified protein was identified as a haptoglobin precursor by peptide mapping with using LC/Q-TOF/MS and MALDI-TOF/MS and this was confirmed by western blotting and ELISA. IgG and IgM in serum were decreased in a dose-dependent manner and IgA was decreased at 7.5 mg/kg bw DON administration, but the IgE level was not changed. To compare the expressions of haptoglobin and the Igs patterns between aflatoxin B1 (AFB1), zearalenone (ZEA) and DON intoxications, rats were orally administered with AFB1 1.0, ZEA 240 and DON 7.5 mg/kg bw for 8 days. Haptoglobin was increased only at DON 7.5 mg/kg bw, while it was slightly decreased at ZEA 240 mg/kg bw and it was not detected at all at AFB1 1.0 mg/kg bw. IgG and IgA were decreased by DON, but IgG, IgA, IgM and IgE were all increased by AFB1. No changes were observed by ZEA administration. These results show that plasma haptoglobin could be a diagnostic biomarker for DON intoxication when this is combined with examining the serum Igs. PMID:18716445

  1. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients.

    PubMed

    Compagno, Nicolò; Cinetto, Francesco; Semenzato, Gianpietro; Agostini, Carlo

    2014-06-01

    Intravenous immunoglobulin replacement therapy represents the standard treatment for hypogammaglobulinemia secondary to B-cell lymphoproliferative disorders. Subcutaneous immunoglobulin infusion is an effective, safe and well-tolerated treatment approach in primary immunodeficiencies but no extensive data are available on their use in secondary hypogammaglobulinemia, a frequent phenomenon occurring after treatment with anti-CD20 monoclonal antibodies in lymphoproliferative disorders. In this retrospective study we evaluated efficacy (serum IgG trough levels, incidence of infections per year, need for antibiotics) and safety (number of adverse events) of intravenous (300 mg/kg/4 weeks) versus subcutaneous (75 mg/kg/week) immunoglobulin replacement therapy in 61 patients. In addition, the impact of the infusion methods on quality of life was compared. All patients were treated with subcutaneous immunoglobulin, and 33 out of them had been previously treated with intravenous immunoglobulin. Both treatments appeared to be effective in replacing Ig production deficiency and in reducing the incidence of infectious events and the need for antibiotics. Subcutaneous immunoglobulin obtained a superior benefit when compared to intravenous immunoglobulin achieving higher IgG trough levels, lower incidence of overall infection and need for antibiotics. The incidence of serious bacterial infections was similar with both infusion ways. As expected, a lower number of adverse events was registered with subcutaneous immunoglobulin, compared to intravenous immunoglobulin, with no serious adverse events. Finally, we observed an improvement in health-related quality of life parameters after the switch to subcutaneous immunoglobulin. Our results suggest that subcutaneous immunoglobulin is safe and effective in patients with hypogammaglobulinemia associated to lymphoproliferative disorders.

  2. 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

  3. [10 years' of production and use of human rabies immunoglobulin in Yugoslavia].

    PubMed

    Romić, M; Tomović, O; Medić, P; Pelević, S; Sindić, M; Popović, M; Gligorović, V; Bogdanović, G; Mitrović, M; Petrović, M; Stankov, S; Lazarević-Ivanc, L; Lalosević, V; Lalosević, D

    2001-01-01

    Application of the rabies immunoglobuline is a compulsory part of the prophylaxis of rabies in all severe, transdermal lesions caused by rabies infected animals. Sylvatic rabies has spread in the past few years throughout the whole Yugoslavia, and human cases of rabies have also been reported in other East European countries. In order to achieve the highest level of rabies prophylaxis, apart from postinfective rabies vaccination, it is necessary to provide passive immunization using specific antibodies against rabies. After successful immunization of the young, healthy volunteers in 1990, National Blood Transfusion Institute, in cooperation with the Pasteur Institute from Novi Sad, prepared the first quantities of immunized plasma by plasmapheresis procedure and human rabies immunoglobuline. Without national production, sufficient quantities of human rabies immunoglobuline could not be provided, since the price on the world market is rather high (over $1000 per patient).

  4. 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.

  5. [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.

  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. Multi-scale modeling of the phase diagram of Human Immunoglobulin

    NASA Astrophysics Data System (ADS)

    Tuchman, Mark; Buldyrev, Sergey; Wang, Ying; Lomakin, Aleksey; Benedek, George B.

    2014-03-01

    Human Immunoglobulin antibodies IGg is a Y-shape trimer consisting of three folded protein globules, connected by two polypeptide hinges in random conformations linked by disulfide bonds. The solubility and crystallization phase diagrams of immunoglobulin are crucial in understanding various pathological conditions. It is experimentally known that the critical volume fraction of immunoglobulin is three times smaller than for typical globular proteins. In order to explain this phenomenon, we perform a multi-scale molecular dynamic (MD) simulations. First we produce all atom simulations of the hinges and compute the distribution of their end-to-end distances. Using these results we construct a simple effective bond potential and study a phase diagram of a system of three sticky hard-spheres linked by these bonds by discrete MD simulations. The results are in good agreement with the experiment.

  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. [Evaluation of the indirect hemagglutination inhibition and radial immunodiffusion tests as methods of quantitative immunoglobulin determination].

    PubMed

    Kukain, E M; Nikolaeva, T A; Khazenson, L B

    1975-03-01

    In comparison with the radial immunodiffusion method, the sensitivity of the indirect hemagglutination test in determining the concentration of immunoglobulins G, M and A in various biological substrates (blood serum, saliva, cerebrospinal fluid, feces) was 35--100 greater. Under the action of proteolytic enzymes immunoglobulin fragmentation led to increase in the concentration of the Ig indices (according to the data of radial immunodiffusion) and produced no effect on the indices of the indirect hemagglutination test; The latter should be used to determine the immunoglobulins in the external secretions characterized by a low content of the given proteins and a marked probability of their proteolytic splitting. In assessing the results of the indirect hemagglutination test it should be remembered that it was less precise and less reproducible than the radial immunodiffusion method.

  10. The impact of glycosylation on the biological function and structure of human immunoglobulins.

    PubMed

    Arnold, James N; Wormald, Mark R; Sim, Robert B; Rudd, Pauline M; Dwek, Raymond A

    2007-01-01

    Immunoglobulins are the major secretory products of the adaptive immune system. Each is characterized by a distinctive set of glycoforms that reflects the wide variation in the number, type, and location of their oligosaccharides. In a given physiological state, glycoform populations are reproducible; therefore, disease-associated alterations provide diagnostic biomarkers (e.g., for rheumatoid arthritis) and contribute to disease pathogenesis. The oligosaccharides provide important recognition epitopes that engage with lectins, endowing the immunoglobulins with an expanded functional repertoire. The sugars play specific structural roles, maintaining and modulating effector functions that are physiologically relevant and can be manipulated to optimize the properties of therapeutic antibodies. New molecular models of all the immunoglobulins are included to provide a basis for informed and critical discussion. The models were constructed by combining glycan sequencing data with oligosaccharide linkage and dynamics information from the Glycobiology Institute experimental database and protein structural data from "The Protein Data Bank."

  11. [Topical corticosteroids as a therapeutic alternative in linear immunoglobulin A bullous dermatosis in childhood: case report].

    PubMed

    Gil Sáenz, Francisco José; Durán Urdániz, Gabriel; Fernández Galar, Marta; Ballester, Juan Gimeno; Herrero Varasa, Ana; Garcés Bordege, Rosa

    2016-12-01

    Linear immunoglobulin A dermatosis of childhood is a rare autoimmune disorder. Its etiology remains unknown, although it has been linked to drugs, infections, immunological diseases and lymphoproliferative processes. We report the case of a 6 year old girl who consulted for perioral bullous lesions without other symptoms. Neither treatment with mupirocin nor methylprednisolone therapy achieved remission of cutaneous lesions. Skin biopsy showed a linear immunoglobulin A dermatosis. It was not possible to start treatment with dapsone because of a partial glucose-6-phosphate dehydrogenase deficiency, so topical treatment was maintained with good evolution of lesions. Linear immunoglobulin A dermatosis is a rare disease whose differential diagnosis includes other bullous diseases. Pathology is essential for diagnosis. When treatment with dapsone is not possible, topical corticosteroids may be an alternative, either alone or associated with other treatments.

  12. 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.

  13. Human immunoglobulin 10 % with recombinant human hyaluronidase: replacement therapy in patients with primary immunodeficiency disorders.

    PubMed

    Sanford, Mark

    2014-08-01

    Human immunoglobulin is an established replacement therapy for patients with primary immunodeficiency disorders (PIDs). Recombinant human hyaluronidase (rHuPH20) is a spreading factor that temporarily digests hyaluronan in the skin interstitium enabling large volumes of fluid or drug solutions to be infused and absorbed subcutaneously. HyQvia® (IGHy) is a new combination product whereby rHuPH20 is injected subcutaneously, followed by human immunoglobulin 10 % infused through the same needle. Thus, IGHy can be administered at a reduced frequency compared with non-facilitated subcutaneous injection of human immunoglobulin, and with a lower frequency of infusion reactions than with intravenous administration. Home-based administration of IGHy is also feasible for adequately trained patients. IGHy was compared with intravenous human immunoglobulin 10 % in a non-randomized, open-label, phase 3 study in patients aged ≥2 years with PIDs who were receiving human immunoglobulin replacement therapy (n = 87). In this study, trough IgG concentrations, acute serious bacterial infection rates (primary endpoint) and occurrences of adverse events during the IGHy treatment period were generally similar to those observed during an intravenous treatment period. IGHy was associated with a numerically lower rate of systemic adverse events and a numerically higher rate of localized adverse events than those observed with intravenous treatment. Compared with intravenous administration, IGHy was administered at a significantly higher maximum flow rate and at a similar frequency. Most patients preferred IGHy over intravenous administration. IGHy offers a new method for subcutaneous delivery of human immunoglobulin replacement therapy in patients with PIDs.

  14. Immunoglobulin M Nephropathy in a Patient with Wilson’s Disease

    PubMed Central

    Sajjad, Zoya; Haroon Khan, Asna; Mamoon, Nadira; Bilal, Muhammad; Mujtaba Quadri, Khaja Hameeduddin

    2016-01-01

    Immunoglobulin M nephropathy (IgMN) is characterized by the deposition of immunoglobulin M in a dominant distribution in the renal glomeruli. Primary immunoglobulin M nephropathy is diagnosed after consistent light microscopy (LM), immunofluorescence (IF), electron microscopy (EM) results, and exclusion of known systemic disorders causing immunoglobulin M deposition in the glomeruli. The secondary disease has been reported with a few conditions though it has never been reported with any primary disease of the liver. We report the case of an adolescent male patient who presented with nausea, vomiting, diarrhea, and worsening anasarca. He was found to have nephrotic-range proteinuria that did not respond to conventional corticosteroid treatment. He was subjected to a renal biopsy which revealed a diagnosis of immunoglobulin M nephropathy. His liver function tests were deranged and an ultrasound scan of the abdomen revealed a coarse irregular liver. Workup revealed elevated urine copper excretion and a low ceruloplasmin level. He was diagnosed as a case of Wilson’s disease and started on penicillamine and pyridoxine. He was also started on intravenous cyclophosphamide for the corticosteroid-resistant nephrotic syndrome to which he responded remarkably well. His edema settled, proteinuria resolved, and liver functions normalized. Currently, he is in remission and enjoying good health. To the best of our knowledge, we report the first known association between IgM nephropathy and Wilson’s disease. It is presently not clear if causation can necessarily be established. This may be the result of defective IgM clearance by the liver or an altered metabolism of the antibody or immune complexes, as with hepatic-associated immunoglobulin M (IgM) nephropathy. Further studies are needed to elucidate the exact mechanism of this disease. PMID:28097080

  15. Glucose Variability

    PubMed Central

    Le Floch, Jean-Pierre; Kessler, Laurence

    2016-01-01

    Background: Glucose variability has been suspected to be a major factor of diabetic complications. Several indices have been proposed for measuring glucose variability, but their interest remains discussed. Our aim was to compare different indices. Methods: Glucose variability was studied in 150 insulin-treated diabetic patients (46% men, 42% type 1 diabetes, age 52 ± 11 years) using a continuous glucose monitoring system (668 ± 564 glucose values; mean glucose value 173 ± 38 mg/dL). Results from the mean, the median, different indices (SD, MAGE, MAG, glucose fluctuation index (GFI), and percentages of low [<60 mg/dL] and high [>180 mg/dL] glucose values), and ratios (CV = SD/m, MAGE/m, MAG/m, and GCF = GFI/m) were compared using Pearson linear correlations and a multivariate principal component analysis (PCA). Results: CV, MAGE/m (ns), GCF and GFI (P < .05), MAG and MAG/m (P < .01) were not strongly correlated with the mean. The percentage of high glucose values was mainly correlated with indices. The percentage of low glucose values was mainly correlated with ratios. PCA showed 3 main axes; the first was associated with descriptive data (mean, SD, CV, MAGE, MAGE/m, and percentage of high glucose values); the second with ratios MAG/m and GCF and with the percentage of low glucose values; and the third with MAG, GFI, and the percentage of high glucose values. Conclusions: Indices and ratios provide complementary pieces of information associated with high and low glucose values, respectively. The pairs MAG+MAG/m and GFI+GCF appear to be the most reliable markers of glucose variability in diabetic patients. PMID:26880391

  16. QT variability.

    PubMed

    Berger, Ronald D

    2003-01-01

    We hypothesized that temporal lability in ventricular repolarization is a marker for, and is mechanistically related to, increased risk of malignant ventricular arrhythmias. To assess repolarization lability in the surface electrocardiogram, we developed an automated algorithm, based on template matching, to measure beat-to-beat changes in QT interval. We calculate a QT variability index (QTVI) to quantify the relative magnitude of QT interval changes compared to heart rate variability. We found that QTVI is a reproducible measure. It is elevated in patients with ischemic and nonischemic dilated cardiomyopathy compared with age-matched controls (P<.00001). We have also shown that QTVI is elevated in patients with malignant beta-myosin heavy-chain mutations associated with hypertrophic cardiomyopathy. In a study of patients undergoing electrophysiologic testing, QTVI identified patients with cardiac arrest better than electrophysiologic test result and better than other risk stratifiers included in the analysis. QT variability is a marker of electrical disease in the ventricle and may be associated with enhanced risk of life-threatening arrhythmias.

  17. [Good response of scleromyxedema and dermato-neuro syndrome to treatment with intravenous immunoglobulins].

    PubMed

    Bielsa, I; Benvenutti, F; Guinovart, R M; Ferrándiz, C

    2012-05-01

    Scleromyxedema is a potentially serious disease that can have various systemic complications. One of the most frequent forms of central nervous system involvement is dermato-neuro syndrome. High-dose intravenous immunoglobulins are among the drug treatments that have been used for this syndrome. We describe 2 patients with scleromyxedema, one of whom developed dermato-neuro syndrome. Both patients responded well to treatment with high-dose intravenous immunoglobulins. We suggest this therapy as a suitable first-line treatment for scleromyxedema and for its neurological complications.

  18. Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

    PubMed

    Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

    2017-02-01

    A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

  19. Effect of water on the temperatures of human immunoglobulin conformation transitions

    NASA Astrophysics Data System (ADS)

    Ur'yash, V. F.; Kokurina, N. Yu.

    2013-10-01

    A differential thermal analysis of native and denaturated human immunoglobulin (G isotype) and mixtures of the native protein with water over the temperature range of 80-570 K is conducted. Temperatures of the protein conformational transitions and the effect of water on them are investigated. The limit of water solubility in the native protein is determined calorimetrically from the enthalpy of excess water phase melting. A physical state diagram of the immunoglobulin-water system over a wide range of temperatures and component concentrations is built and analyzed.

  20. Relationships between day one piglet serum immunoglobulin immunocrit and subsequent growth, puberty attainment, litter size, and lactation performance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Colostrum affects gut and uterine gland development in the neonatal piglet, suggesting that subsequent growth and reproductive performance may be affected. Measuring immunoglobulin in piglet serum using the immunoglobulin immunocrit on day 1 of age provides a simple inexpensive indication of the amo...

  1. Immunoglobulins A, G, and M in serum and in some secretions of monkeys (Macaca fascicularis syn. irus).

    PubMed Central

    Cole, M F; Bowen, W H

    1976-01-01

    The purpose of this investigation was to study the distribution and levels of the following immunoglobulins, IgA, IgG, and IgM ,in sera and in some secretions of monkeys (M. fascicularis). IgG, IgA, and IgM were isolated from monkey serum and secretory IgA was separated from monkey milk by combined gel filtration and ion-exchange chromatography. These pure preparations served as standards to quantitate immunoglobulins in sera and secretions by single radial immunodiffusion. Antisera were raised in the rabbit against the pure immunoglobulins and also against the whole secretions to identify the immunoglobulins in immunoelectrophoresis. In common with humans, the major immunoglobulin in serum and amniotic fluid is IgG and the IgG/IgA ratio is greater than unity. In secretions IgA is the dominant immunoglobulin and the IgG/IgA ratio is less than 1. In general, the levels of immunoglobulins in the sera and secretions of monkeys paralleled the levels found in humans. No age-related increase in immunoglobulin levels was detected in the sera of monkeys. PMID:818024

  2. 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

  3. 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

  4. Heterogeneity of nonimmune immunoglobulin Fc reactivity among gram-positive cocci: description of three major types of receptors for human immunoglobulin G.

    PubMed

    Myhre, E B; Kronvall, G

    1977-09-01

    Two hundred and thirty strains of various gram-positive cocci were tested for quantitative, nonimmune binding of radiolabeled human polyclonal immunoglobulin G (IgG). The majority of coagulase-positive staphylococci and streptococci belonging to serogroups C and G showed a high uptake of IgG. The binding of immunoglobulin to group A streptococci was considerably less, with a number of strains completely negative. None of the pneumococcal or the group B or D streptococcal strains displayed any binding capacity. Heterogeneity of the IgG reactivity of various reactive strains was studied in an inhibition assay using 10 different animal serum pools. Three different inhibition patterns were seen, each of them revealing a striking degree of homogeneity within single bacterial species. Staphylococcus aureus and group A streptococci, respectively, constituted two homogeneous groups which differed markedly from each other and from C and G streptococci. No differences were observed between group C and G streptococci. Based on the profound differences between these homogeneous groups, three major types of Fc receptors could be defined. Type I and II Fc receptors were found on S. aureus and on group A streptococci, respectively. Fc receptor type III represented the immunoglobulin-binding structure of both group C and G streptococci.

  5. Chronic inflammatory demyelinating polyneuropathy in common variable immunodeficiency.

    PubMed

    Özdemir, Özlem; Okan, Mehmet S; Kilic, Sara S

    2012-04-01

    Common variable immunodeficiency comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunologic phenotypes. Immune dysregulation leads to the generation of multiple autoantibodies against various antigenic targets in patients with common variable immunodeficiency. Chronic inflammatory demyelinating polyneuropathy is a heterogeneous disorder that indicates an autoimmune response against peripheral nerve myelin. We describe a 7-year-old girl with common variable immunodeficiency who developed chronic inflammatory polyneuropathy. A 5-day course of intravenous immunoglobulin (500 mg/kg/day) improved her neurologic disorder. Chronic inflammatory demyelinating polyneuropathy should be added to the broadening spectrum of neurologic complications in common variable immunodeficiency. Early detection and consequent treatment may reverse the neurologic sequelae.

  6. 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

  7. Immunoglobulin Replacement Therapy: When You Need It -- and When You Don't

    MedlinePlus

    ... Replacement Therapy Immunoglobulin Replacement Therapy When you need it—and when you don’t DOWNLOAD PDF Some ... the treatment even though they don’t need it. That’s not a good idea. Here’s why. The ...

  8. 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...

  9. 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...

  10. 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...

  11. Immunoglobulin G4-Related Inflammatory Abdominal Aortic Aneurysm Associated With Myasthenia Gravis, With Contained Rupture.

    PubMed

    Jun, Heungman; Jung, Cheol Woong

    2016-11-01

    Immunoglobulin (Ig) G4-related disease is reportedly among the various causes of inflammatory abdominal aortic aneurysm (IAAA). Many IgG4-related diseases are closely related to allergic constitution and autoimmune disease. We report a case of a 72-year-old man with IgG4-related IAAA associated with myasthenia gravis, with contained rupture.

  12. 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

  13. 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.

  14. Immunoglobulin deposits in labial mucosal epithelium of patients suspected of Sjögren's syndrome.

    PubMed

    Oxholm, P; Manthorpe, R; Oxholm, A; Schiødt, M

    1986-02-01

    Lower lip biopsies from twenty-three consecutive patients under evaluation for Sjögren's syndrome, and from six normal controls, were investigated for deposits of immunoglobulins, fibrinogen and C3, using a direct immunofluorescence technique. Deposits of both IgG and IgA were demonstrated in the mucosal epithelium in three of six patients with primary Sjögren's syndrome. Similar IgG deposits were found in two of three patients with xerostomia and in one of three patients with Sjögren's syndrome secondary to rheumatoid arthritis. Immunoglobulins were located in close relation to cell surfaces in the basal and suprabasal layers of the epithelium. Double labelling experiments indicated a partial topographic concordance between the immunoglobulin deposits and OKT6 positive Langerhans cells in the epithelium. No deposits of immunoglobulins, fibrinogen or C3 were found in the remaining eleven patients and six normal controls. We conclude that deposits of IgG and IgA in the labial mucosal epithelium seem to be a characteristic finding in patients with primary Sjögren's syndrome as well as in patients with xerostomia. The diagnostic value of this new observation needs to be clarified in future studies.

  15. Immunoassay of Mouse Immunoglobulin G by a Light-Addressable Potentiometric Sensor

    DTIC Science & Technology

    1991-04-01

    a liquid phase followed by streptavidin-biotin mediated filtration onto biotinylated nitrocellulose membrane (3). The immobilized enzyme, urease ...employed a high affinity biotin-streptavidin interaction to capture the immunocomplexes onto nitrocellulose membranes, and a urease -conjugated anti-mouse...is presented. UNCLASSIFIED UNCLASSFI ED 3 MATERIALS AND METHODS Reagents Mouse immunoglobulin G, biotinylated anti-mouse IgG (goat), urease

  16. Coexistence of immunoglobulin M nephropathy and autoimmune hemolytic anemia: 2 rare entities.

    PubMed

    Bayrakci, Nergiz; Ozkayar, Nihal; Ersozen, Muge Erek; Colak, Aysel; Oguz, Ebru Gok; Dede, Fatih

    2015-11-01

    Immunoglobulin M (IgM) nephropathy is described as mesengial proliferative glomerulonephritis with diffuse mesengial IgM deposition. We report a patient diagnosed with IgM nephropathy and concomitant autoimmune hemolytic anemia syndrome associated with cold-reacting autoantibodies. Complete remission was achieved with systemic corticosteroid and plasmapheresesis.

  17. Treatment of rotavirus-associated diarrhea using enteral immunoglobulins for pediatric stem cell transplant patients.

    PubMed

    Williams, Devona

    2015-06-01

    Diarrhea is a common complication associated with allogeneic and autologous stem cell transplant patients. One potential cause of viral diarrhea is rotavirus gastroenteritis. This study represents a single-center experience of using multiple daily doses of enteral immunoglobulins in four pediatric hematopoietic stem cell transplant patients with confirmed rotavirus infections. Four courses of enteral immunoglobulin administration were included for analysis. Clinical characteristics recorded included duration of diarrhea symptoms, frequency of bowel movements, and consistency of stool. Four single courses of enteral immunoglobulins in four patients were included for analysis. Patient age range was from 10 months to 14 years. Three out of four courses observed displayed an improvement in diarrhea frequency and/or stool consistency. Median time from therapy initiation to symptom improvement was three days. At a median 22-month follow-up, one patient was diagnosed with gastrointestinal graft-versus-host disease. The time to rotavirus symptom resolution was decreased, compared to historical controls, and improvement in stool frequency and consistency was observed in three of four courses. One case of gastrointestinal graft-versus-host disease was observed after nearly two years of follow-up. Enteral administration of immunoglobulins may represent a valid clinical option for hematopoietic stem cell transplant patients with rotavirus diarrhea.

  18. High incidence of intact or fragmented immunoglobulin in urine of patients with multiple myeloma.

    PubMed

    Kraj, Maria; Kruk, Barbara; Lech-Marańda, Ewa; Warzocha, Krzysztof; Prochorec-Sobieszek, Monika

    2015-01-01

    In this prospective study we determined the incidence of intact/fragmented immunoglobulin and Bence Jones protein in urine immunofixation using Sebia reagents and HydrasysTM 2 apparatus and compared the results to concentrations of serum free light chains (FLC) assessed using Siemens BNTM II nephelometer and the immunoassay Freelite (Binding Site) in 289 patients with multiple myeloma at diagnosis. It was found that in one third of IgG, IgA and IgD myeloma patients, intact/fragmented immunoglobulin can be detected in urine and is connected with impaired renal function and reduced survival. Urine immunofixation detects monoclonal protein (FLC and intact/fragmented immunoglobulin) in 66-79% of IgG and IgA myeloma patients while serum FLC immunoassay detect it in 82-94% of IgG and IgA myeloma patients. However, the latter method is inadequate for detection of intact/fragmented immunoglobulin in urine. Serum FLC immunoassay and urine immunofixation are complementary methods in diagnosing and monitoring monoclonal protein in patients with myeloma.

  19. Receptor Inhibition by Immunoglobulins: Specific Inhibition by Autistic Children, Their Relatives, and Control Subjects.

    ERIC Educational Resources Information Center

    Cook, Edwin H., Jr.; And Others

    1993-01-01

    Forty-two parents of children with autistic disorder, 15 children with autistic disorder, 17 siblings of children with autistic disorder, and 12 unrelated normal controls were studied for binding characteristics of their immunoglobulins. Results did not support the hypothesis that two specific autoantibodies are characteristic of autism.…

  20. [Secretory immunoglobulin A in the amniotic fluid of healthy pregnant females].

    PubMed

    Briese, V; Straube, W; Brock, J; Stark, K H; Lorenz, U

    1983-01-01

    Amniotic fluid levels of secretory immunoglobulin A (S-AgA) were measured by simple radial immunodiffusion according to the method of Mancini using a monospecific antiserum against the human secretory component. 256 samples from healthy pregnant women were examined. Amniotic fluid S-IgA concentration increases significantly during normal pregnancy and shows a loose correlation to the phospholipid level.