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Sample records for nonphysiological immunoglobulin variable

  1. Exceptional Amyloid β Peptide Hydrolyzing Activity of Nonphysiological Immunoglobulin Variable Domain Scaffolds*S⃞

    PubMed Central

    Taguchi, Hiroaki; Planque, Stephanie; Sapparapu, Gopal; Boivin, Stephane; Hara, Mariko; Nishiyama, Yasuhiro; Paul, Sudhir

    2008-01-01

    Nucleophilic sites in the paired variable domains of the light and heavy chains (VL and VH domains) of Ig can catalyze peptide bond hydrolysis. Amyloid β (Aβ)-binding Igs are under consideration for immunotherapy of Alzheimer disease. We searched for Aβ-hydrolyzing human IgV domains (IgVs) in a library containing a majority of single chain Fv clones mimicking physiological VL-VH-combining sites and minority IgV populations with nonphysiological structures generated by cloning errors. Random screening and covalent selection of phage-displayed IgVs with an electrophilic Aβ analog identified rare IgVs that hydrolyzed Aβ mainly at His14-Gln15. Inhibition of IgV catalysis and irreversible binding by an electrophilic hapten suggested a nucleophilic catalytic mechanism. Structural analysis indicated that the catalytic IgVs are nonphysiological structures, a two domain heterodimeric VL (IgVL2-t) and single domain VL clones with aberrant polypeptide tags (IgVL-t′). The IgVs hydrolyzed Aβ at rates superior to naturally occurring Igs by 3-4 orders of magnitude. Forced pairing of the single domain VL with VH or VL domains resulted in reduced Aβ hydrolysis, suggesting catalysis by the unpaired VL domain.Ångstrom level amino acid displacements evident in molecular models of the two domain and unpaired VL domain clones explain alterations of catalytic activity. In view of their superior catalytic activity, the VL domain IgVs may help attain clearance of medically important antigens more efficiently than natural Igs. PMID:18974093

  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. PMID:26791019

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

    PubMed

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

    2015-11-01

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

  4. Subclustering of human immunoglobulin kappa light chain variable region genes

    SciTech Connect

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

    1993-04-01

    The human immunoglobulin kappa light chain (IgK) locus includes multiple variable region gene segments (V[sub k]) that can be divided into four subgroups. Oligonucleotide primers were designed to amplify specifically gene segments of the V[sub k]I, V[sub k]II, and V[sub k]III subgroups using the polymerase chain reaction (PCR). Product sequences were subcloned, sequenced, and compared. Phylogenetic analyses of sequences within each subgroup indicate that some subgroups can be subdivided further into [open quotes]sub-subgroups.[close quotes] The history of V[sub k] segment duplications apparently includes at least two separate periods, the first giving rise to the subgroups and the second generating further complexity within each subgroup. Duplications of large pieces of DNA (demonstrated by others through pulsed-field gel electrophoresis) also played a role. Rates of synonymous and nonsynonymous base changes between pairs of sequences suggest that natural selection has played a major role in the evolution of the V[sub k] variable gene segments, leading to sequence conservation in some regions and to increased diversity in others. 34 refs., 4 figs., 3 tabs.

  5. Developmental progression of equine immunoglobulin heavy chain variable region diversity.

    PubMed

    Tallmadge, Rebecca L; Tseng, Chia T; King, Rebecca A; Felippe, M Julia B

    2013-09-01

    Humoral immunity is a critical component of the immune system that is established during fetal life and expands upon exposure to pathogens. The extensive humoral immune response repertoire is generated in large part via immunoglobulin (Ig) heavy chain variable region diversity. The horse is a useful model to study the development of humoral diversity because the placenta does not transfer maternal antibodies; therefore, Igs detected in the fetus and pre-suckle neonate were generated in utero. The goal of this study was to compare the equine fetal Ig VDJ repertoire to that of neonatal, foal, and adult horse stages of life. We found similar profiles of IGHV, IGHD, and IGHJ gene usage throughout life, including predominant usage of IGHV2S3, IGHD18S1, and IGHJ1S5. CDR3H lengths were also comparable throughout life. Unexpectedly, Ig sequence diversity significantly increased between the fetal and neonatal age, and, as expected, between the foal and adult age. PMID:23567345

  6. Rapid cloning of any rearranged mouse immunoglobulin variable genes

    SciTech Connect

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

    1996-12-31

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

  7. Thrombocytopenia in common variable immunodeficiency patients – clinical course, management, and effect of immunoglobulins

    PubMed Central

    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. PMID:26155188

  8. Renal granuloma and immunoglobulin M-complex glomerulonephritis: a case of common variable immunodeficiency?

    PubMed

    Benoit, Geneviève; Lapeyraque, Anne-Laure; Sartelet, Hervé; Saint-Cyr, Claire; Le Deist, Françoise; Haddad, Elie

    2009-03-01

    Common variable immunodeficiency (CVID) is characterized by reduced serum immunoglobulin levels and recurrent bacterial infections. Granulomatous infiltrations are occasionally found in the lymphoid or solid organs of affected patients, but renal involvement is rare. We present a case of possible CVID with interstitial noncaseating granuloma and immunoglobulin (IgM)-complex glomerulonephritis with a membranoproliferative pattern and with a favorable response to corticosteroids, intravenously administered immunoglobulins (IVIGs) and rituximab. CVID must be included in the differential diagnosis of renal granuloma and should be differentiated from sarcoidosis to ensure appropriate therapy. PMID:18696117

  9. Recurrent myelitis in common variable immunodeficiency successfully managed with high-dose subcutaneous immunoglobulin.

    PubMed

    Danieli, Maria Giovanna; Pettinari, Lucia; Marinangeli, Lucia; Logullo, Francesco

    2012-01-01

    Acute myelitis is an aetiologically heterogeneous inflammatory disorder of the spinal cord. We report on a 71-year-old woman with a recurrent cervical and thoracic myelitis who presented with a new relapse of the disease. Neuromyelitis optica was ruled out such as other possible causes of acute and/or recurrent myelopathy. Serum immunoglobulin levels and specific antibody responses were consistent with the diagnosis of common variable immunodeficiency (CVID). She was treated with high-dose methylprednisolone and intravenous immunoglobulin. As a remission-maintaining drug, we decided to treat her with subcutaneous immunoglobulin (CSL Behring) at 0.2 g/kg/week at doses higher than usually employed in replacement therapy in CVID. At 3-year follow-up, the response to treatment was good. No relapses occurred. Our case suggests the effectiveness and safety of subcutaneous immunoglobulin in maintaining remission and in sparing prednisone in a woman with recurrent myelitis associated with CVID. PMID:22878981

  10. Recurrent myelitis in common variable immunodeficiency successfully managed with high-dose subcutaneous immunoglobulin

    PubMed Central

    Danieli, Maria Giovanna; Pettinari, Lucia; Marinangeli, Lucia; Logullo, Francesco

    2012-01-01

    Acute myelitis is an aetiologically heterogeneous inflammatory disorder of the spinal cord. We report on a 71-year-old woman with a recurrent cervical and thoracic myelitis who presented with a new relapse of the disease. Neuromyelitis optica was ruled out such as other possible causes of acute and/or recurrent myelopathy. Serum immunoglobulin levels and specific antibody responses were consistent with the diagnosis of common variable immunodeficiency (CVID). She was treated with high-dose methylprednisolone and intravenous immunoglobulin. As a remission-maintaining drug, we decided to treat her with subcutaneous immunoglobulin (CSL Behring) at 0.2 g/kg/week at doses higher than usually employed in replacement therapy in CVID. At 3-year follow-up, the response to treatment was good. No relapses occurred. Our case suggests the effectiveness and safety of subcutaneous immunoglobulin in maintaining remission and in sparing prednisone in a woman with recurrent myelitis associated with CVID. PMID:22878981

  11. [Lupus nephritis associated with common variable immunodeficiency: favourable outcome with intravenous immunoglobulin treatment].

    PubMed

    Geneviève, M; Bonnet, F; Michaux, C; Geffroy, C-E; Vandenhende, M-A; Combe, C; Morlat, P

    2012-06-01

    We report a 24-year-old woman who presented with a nephrotic syndrome as the revealing manifestation of systemic lupus erythematosus (SLE) and an associated hypogammaglobulinemia related to a common variable immunodeficiency (CVID). Outcome of SLE was favourable with intravenous immunoglobulin treatment solely. Relationships between SLE and CVID are discussed. PMID:22560369

  12. Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes*

    PubMed Central

    Janda, Alena; Eryilmaz, Ertan; Nakouzi, Antonio; Cowburn, David; Casadevall, Arturo

    2012-01-01

    The finding that the antibody (Ab) constant (C) region can influence fine specificity suggests that isotype switching contributes to the generation of Ab diversity and idiotype restriction. Despite the centrality of this observation for diverse immunological effects such as vaccine responses, isotype-restricted antibody responses, and the origin of primary and secondary responses, the molecular mechanism(s) responsible for this phenomenon are not understood. In this study, we have taken a novel approach to the problem by probing the paratope with 15N label peptide mimetics followed by NMR spectroscopy and fluorescence emission spectroscopy. Specifically, we have explored the hypothesis that the C region imposes conformational constraints on the variable (V) region to affect paratope structure in a V region identical IgG1, IgG2a, IgG2b, and IgG3 mAbs. The results reveal isotype-related differences in fluorescence emission spectroscopy and temperature-related differences in binding and cleavage of a peptide mimetic. We conclude that the C region can modify the V region structure to alter the Ab paratope, thus providing an explanation for how isotype can affect Ab specificity. PMID:22930758

  13. Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions

    PubMed Central

    Maul, Robert W; Saribasak, Huseyin; Martomo, Stella A; McClure, Rhonda L; Yang, William; Vaisman, Alexandra; Gramlich, Hillary S; Schatz, David G; Woodgate, Roger; Wilson, David M; Gearhart, Patricia J

    2013-01-01

    Activation-induced deaminase (AID) initiates diversity of immunoglobulin genes through deamination of cytosine to uracil. Two opposing models have been proposed for the deamination of DNA or RNA by AID. Although most data support DNA deamination, there is no physical evidence of uracil residues in immunoglobulin genes. Here we demonstrate their presence by determining the sensitivity of DNA to digestion with uracil DNA glycosylase (UNG) and abasic endonuclease. Using several methods of detection, we identified uracil residues in the variable and switch regions. Uracil residues were generated within 24 h of B cell stimulation, were present on both DNA strands and were found to replace mainly cytosine bases. Our data provide direct evidence for the model that AID functions by deaminating cytosine residues in DNA. PMID:21151102

  14. Cloning of multiple copies of immunoglobulin variable kappa genes in cosmid vectors.

    PubMed Central

    Cattaneo, R; Gorski, J; Mach, B

    1981-01-01

    The possibility of cloning large segments of DNA in cosmid vectors offers distinct advantages, in particular for the study of multigene families. Large size fragments of mouse embryo DNA were successfully cloned in the cosmid pHC 79. Twelve recombinants hybridizing specifically to an immunoglobulin kappa chain variable region probe were identified. In 9 of these recombinants, the size of the insert ranges from 30 to 43 kilobases. Factors affecting the cloning efficiency of a complex mammalian genome in cosmids were studied. The stability of these recombinant cosmids and the preparation of recombinant cosmid DNA are also discussed. Images PMID:6269060

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

    PubMed Central

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

    2014-01-01

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

  16. Intravenous immunoglobulin induces proliferation and immunoglobulin synthesis from B cells of patients with common variable immunodeficiency: a mechanism underlying the beneficial effect of IVIg in primary immunodeficiencies.

    PubMed

    Bayry, Jagadeesh; Fournier, Emilie M; Maddur, Mohan S; Vani, Janakiraman; Wootla, Bharath; Sibéril, Sophie; Dimitrov, Jordan D; Lacroix-Desmazes, Sébastien; Berdah, Mikael; Crabol, Yoann; Oksenhendler, Eric; Lévy, Yves; Mouthon, Luc; Sautès-Fridman, Catherine; Hermine, Olivier; Kaveri, Srini V

    2011-02-01

    Common variable immunodeficiency (CVID) is associated with low serum immunoglobulin concentrations and an increased susceptibility to infections and autoimmune diseases. The treatment of choice for CVID patients is replacement intravenous immunoglobulin (IVIg) therapy. IVIg has been beneficial in preventing or alleviating the severity of infections and autoimmune and inflammatory process in majority of CVID patients. Although the mechanisms of action of IVIg given as 'therapeutic high dose' in patients with autoimmune diseases are well studied, the underlying mechanisms of beneficial effects of IVIg in primary immunodeficiencies are not completely understood. Therefore we investigated the effect of 'replacement dose' of IVIg by probing its action on B cells from CVID patients. We demonstrate that IVIg at low doses induces proliferation and immunoglobulin synthesis from B cells of CVID patients. Interestingly, B cell stimulation by IVIg is not associated with induction of B cell effector cytokine IFN-γ and of transcription factor T-bet. Together, our results indicate that in some CVID patients, IVIg rectifies the defective signaling of B cells normally provided by T cells and delivers T-independent signaling for B cells to proliferate. IVIg 'replacement therapy' in primary immunodeficiencies is therefore not a merepassive transfer of antibodies to prevent exclusively the recurrent infections; rather it has an active role in regulating autoimmune and inflammatory responses through modulating B cell functions and thus imposing dynamic equilibrium of the immune system. PMID:20970960

  17. Conserved aromatic residues as determinants in the folding and assembly of immunoglobulin variable domains.

    PubMed

    Campion, Stephen R

    2016-02-01

    Detailed analysis of amino acid distribution, focusing on the "framework" regions of both heavy- and light-chain variable immunoglobulin (Ig) domains, distinguished those conserved sequence elements shared by both heavy-chain (VH) and light-chain (VL) domains from those conserved determinants unique to either VH or VL domains alone. Mapping of conserved chemical functionality onto characterized PDB structures showed the analogous placement and utilization of shared determinants in VH and VL structures that are generally similar. Identical Arginine-Aspartic acid ion-pairs located symmetrically on the lateral surfaces of VH and VL domains, respectively, as well as paired glutamine residues that constitute a central contact site between VH and VL domains represent clearly shared molecular features. Three sites of shared aromaticity were found localized to symmetrical sites lining the inaccessible interface of the VH-VL duplex, suggesting an expanded role for strategically conserved aromatic residues from a postulated determinant of individual Ig domain folding to now implicate conserved aromatic sites in the subsequent multi-subunit assembly of native antibody superstructure. Differential domain-specific conservation, representing evolutionary diversification and molecular asymmetry between heavy- and light-chain variable domains was limited, but included amino acids from each functional class and must be evaluated with regard to their possible involvement in heterologous aspects of IgV protein structure-function. PMID:26742085

  18. Immunoglobulin kappa light chain variable region gene complex organization and immunoglobulin genes encoding anti-DNA autoantibodies in lupus mice.

    PubMed Central

    Kofler, R; Strohal, R; Balderas, R S; Johnson, M E; Noonan, D J; Duchosal, M A; Dixon, F J; Theofilopoulos, A N

    1988-01-01

    We have investigated the genetic origin of autoantibody production in several strains of mice that spontaneously develop a systemic lupus erythematosus-like disease. Restriction fragment length polymorphism analyses of gene loci encoding kappa light chain variable regions (Igk-V) demonstrated, as shown previously for the Ig heavy chain locus, that autoantibody production and disease occur in different Igk-V haplotypes. Moreover, autoimmune mice with known genetic derivation inherited their Igk-V loci essentially unaltered from their nonautoimmune ancestors. New Zealand black lupus mice, with unknown genetic derivation, had a possibly recombinant Igk-V haplotype, composed of V kappa loci that were primarily indistinguishable from those of nonautoimmune strains from either of the two potential donor haplotypes. The heavy and light chain gene segments (variable, diversity, joining) encoding anti-DNA antibodies were diverse and often closely related, or even identical, to those found in antibodies to foreign antigens in normal mice. Only 1 of 11 sequenced variable region genes could not be assigned to existing variable region gene families; however, corresponding germline genes were present in the genome of normal mice as well. These data argue against abnormalities in the genes and mechanisms generating antibody diversity in lupus mice and suggest a remarkable genetic and structural diversity in the generation of anti-DNA binding sites. Images PMID:3138286

  19. 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

  20. Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain

    PubMed Central

    Brumshtein, Boris; Esswein, Shannon R; Salwinski, Lukasz; Phillips, Martin L; Ly, Alan T; Cascio, Duilio; Sawaya, Michael R; Eisenberg, David S

    2015-01-01

    Overproduction of immunoglobulin light chains leads to systemic amyloidosis, a lethal disease characterized by the formation of amyloid fibrils in patients' tissues. Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. Here we identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer. DOI: http://dx.doi.org/10.7554/eLife.10935.001 PMID:26576950

  1. Immunoglobulin VH clan and family identity predicts variable domain structure and may influence antigen binding.

    PubMed Central

    Kirkham, P M; Mortari, F; Newton, J A; Schroeder, H W

    1992-01-01

    Mammalian immunoglobulin VH families can be grouped into three distinct clans based upon sequence conservation in two of the three framework (FR) intervals. Through replacement/silent site substitution analysis, molecular modeling and mathematical evaluation of known immunoglobulin crystal structures, we demonstrate that this conservation reflects preservation of protein sequence and structure. Each clan contains a characteristic FR 1 interval that is solvent-exposed and structurally separated from the antigen binding site. Families within a clan contain their own unique FR 3 interval that is capable of either influencing the conformation of the antigen binding site or interacting directly with antigen. Our results provide a structural context for theories that address differential use of VH families in the immune response. Images PMID:1537339

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

    PubMed

    Gharib, Asal; Caperton, Caroline; Gupta, Sudhir

    2016-01-01

    Although severe reactions to immunoglobulin preparations have been frequently reported, IgE antibodies against IgA are usually not investigated; and occur predominantly in previously sensitized patients. The purpose is to report anaphylaxis to IGIV during initial infusion in a patient with common variable immunodeficiency with absent IgA without prior sensitization and in the absence of detectable IgG anti-IgA antibodies, and positive skin tests for immediate hypersensitivity to four different preparations of IGIV, one subcutaneous immunoglobulin preparation, and to purified IgA. Patient was treated without side effects with IGIV preparation depleted of IgA to which immediate hypersensitivity skin test was negative. This case demonstrates that patients with CVID with no IgA and without prior exposure to immunoglobulin or plasma may develop anaphylaxis following initial infusion of IGIV, which appears to be due to IgE anti-IgA, and independent of IgG anti-IgA antibodies. Since there is no good correlation between anaphylaxis/anaphylactic reactions and IgG anti-IgA antibodies, and IgE anti-IgA antibody test is commercially unavailable, we suggest that the patients with CVID with absence of IgA might be skin tested for immediate hypersensitivity prior to initiation of immunoglobulin administration. However, such recommendation may require studies on a large number of patients with CVID with no detectable IgA. PMID:27190527

  3. Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived from rheumatoid synovial tissue.

    PubMed

    Brown, C M; Longhurst, C; Haynes, G; Plater-Zyberk, C; Malcolm, A; Maini, R N

    1992-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin VH gene repertoire of eight IgM- and 10 IgG-secreting synovial-derived hybridomas. The VH4 gene family is highly represented (38.5%) in this panel of hybridomas compared with the frequency of VH4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the VH4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of VH4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The VH gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of VH4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia. PMID:1379132

  4. In vivo modulation of the expressions of Fas and CD25 by intravenous immunoglobulin in common variable immunodeficiency.

    PubMed

    Artac, Hasibe; Kara, Reyhan; Reisli, Ismail

    2010-03-01

    Although the presence of physiologic anti-CD95 (Fas, APO-1) autoantibodies in intravenous immunoglobulin (IVIG) preparations is known, the effects of these antibodies in patients with common variable immunodeficiency are unclear (CVID). The aim of the study was to assess the effects of IVIG in Fas expression, activation markers and the subsets of T cells in patients with CVID. We studied 15 cases with CVID and 10 healthy controls with no signs of immunodeficiency. The Fas expression of T cells, activation markers (CD25, CD69 and HLA-DR) and T-cell subsets were analyzed by four-color flow cytometry. We found that the Fas expression of CD3+ T cells in patients was significantly higher than in controls. In addition, there was a significant increase in the Fas expression of CD3+ T cells and CD4+ T cells, and the CD25 expression of CD3+ and CD4+ T cells after IVIG supplementation (P < 0.05). The CD69 and HLA-DR expressions of T cells and CD8+ T cells were not affected by IVIG infusion. Our observation showed that IVIG replacement causes an increase in the Fas and CD25 expressions in patients with CVID. These data suggest that the Fas protein may have an important role in the effects of IVIG for the control of autoimmunity in patients with CVID, as well as in the generation of autoimmune disease. PMID:19730984

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

    PubMed Central

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

    2015-01-01

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

  6. Immunoglobulin heavy chain variable region gene repertoire and B-cell receptor stereotypes in Indian patients with chronic lymphocytic leukemia.

    PubMed

    Rani, Lata; Mathur, Nitin; Gogia, Ajay; Vishnubhatla, Sreenivas; Kumar, Lalit; Sharma, Atul; Dube, Divya; Kaur, Punit; Gupta, Ritu

    2016-10-01

    In chronic lymphocytic leukemia (CLL), the geographical bias in immunoglobulin heavy-chain variable (IGHV) gene usage lead us to analyze IGHV gene usage and B-cell receptor stereotypy in 195 patients from India. IGHV3, IGHV4, and IGHV1 families were the most frequently used. 20.5% sequences had stereotyped BCR and were clustered in 12 pre-defined and 6 novel subsets. Unmutated IGHV was significantly associated with reduced time to first treatment (p < 0.033) and poor overall survival (OS; p = 0.01). We observed a significant difference in OS between IGHV1, IGHV3, and IGHV4 family cases (p = 0.045) in early stage patients. Regarding subfamily usage, only IGHV1-69 expression was found to have statistically significant poor outcome (p = 0.017). Our results from the analysis of various molecular and clinical features suggest that the expression of specific IGHV gene influences the outcome in early stage CLL, and hence its assessment may be added to the clinical leukemia laboratory armamentarium. PMID:26942309

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

    PubMed Central

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

    1986-01-01

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

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

    PubMed

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

    2015-11-01

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

  9. Over 30% of patients with splenic marginal zone lymphoma express the same immunoglobulin heavy variable gene: ontogenetic implications.

    PubMed

    Bikos, V; Darzentas, N; Hadzidimitriou, A; Davis, Z; Hockley, S; Traverse-Glehen, A; Algara, P; Santoro, A; Gonzalez, D; Mollejo, M; Dagklis, A; Gangemi, F; Bosler, D S; Bourikas, G; Anagnostopoulos, A; Tsaftaris, A; Iannitto, E; Ponzoni, M; Felman, P; Berger, F; Belessi, C; Ghia, P; Papadaki, T; Dogan, A; Degano, M; Matutes, E; Piris, M A; Oscier, D; Stamatopoulos, K

    2012-07-01

    We performed an immunogenetic analysis of 345 IGHV-IGHD-IGHJ rearrangements from 337 cases with primary splenic small B-cell lymphomas of marginal-zone origin. Three immunoglobulin (IG) heavy variable (IGHV) genes accounted for 45.8% of the cases (IGHV1-2, 24.9%; IGHV4-34, 12.8%; IGHV3-23, 8.1%). Particularly for the IGHV1-2 gene, strong biases were evident regarding utilization of different alleles, with 79/86 rearrangements (92%) using allele (*)04. Among cases more stringently classified as splenic marginal-zone lymphoma (SMZL) thanks to the availability of splenic histopathological specimens, the frequency of IGHV1-2(*)04 peaked at 31%. The IGHV1-2(*)04 rearrangements carried significantly longer complementarity-determining region-3 (CDR3) than all other cases and showed biased IGHD gene usage, leading to CDR3s with common motifs. The great majority of analyzed rearrangements (299/345, 86.7%) carried IGHV genes with some impact of somatic hypermutation, from minimal to pronounced. Noticeably, 75/79 (95%) IGHV1-2(*)04 rearrangements were mutated; however, they mostly (56/75 cases; 74.6%) carried few mutations (97-99.9% germline identity) of conservative nature and restricted distribution. These distinctive features of the IG receptors indicate selection by (super)antigenic element(s) in the pathogenesis of SMZL. Furthermore, they raise the possibility that certain SMZL subtypes could derive from progenitor populations adapted to particular antigenic challenges through selection of VH domain specificities, in particular the IGHV1-2(*)04 allele. PMID:22222599

  10. Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids

    PubMed Central

    Pinheiro, Ana; Lanning, Dennis; Alves, Paulo C.; Mage, Rose G.; Knight, Katherine L.; van der Loo, Wessel; Esteves, Pedro J.

    2012-01-01

    The rabbit has long been a model for studies of the immune system. Work using rabbits contributed both to the battle against infectious diseases such as rabies and syphilis, and to our knowledge of antibodies' structure, function, and regulated expression. With the description of rabbit Ig allotypes, the discovery of different gene segments encoding immunoglobulins became possible. This challenged the “one gene-one protein” dogma. The observation that rabbit allotypic specificities of the variable regions were present on IgM and IgG molecules also led to the hypothesis of Ig class switching. Rabbit allotypes contributed to the documentation of phenomena such as allelic exclusion and imbalance in production of allelic gene products. During the last 30 years, the rabbit Ig allotypes revealed a number of unique features, setting them apart from mice, humans and other mammals. Here, we review the most relevant findings concerning the rabbit IGHV. Among these are the preferential usage of one VH gene in VDJ rearrangements, the existence of trans-species polymorphism in the IGHV locus revealed by serology and confirmed by sequencing IGHV genes in Lepus, the unusually large genetic distances between allelic lineages and the fact that the antibody repertoire is diversified in this species only after birth. The Whole Genome Sequence of rabbit, plus re-sequencing of additional strains and related genera, will allow further evolutionary investigations of antibody variation. Continued research will help define the roles that genetic, allelic and population diversity at antibody loci may play in host-parasite interactions. PMID:21594770

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

    PubMed

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

    2013-11-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Ng, Kevin Kit; Gould, Paul A.

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. Total proteome analysis identifies migration defects as a major pathogenetic factor in immunoglobulin heavy chain variable region (IGHV)-unmutated chronic lymphocytic leukemia.

    PubMed

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

    2015-04-01

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

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

    PubMed Central

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

    2014-01-01

    Amphioxus is regarded as an essential animal model for the study of immune evolution. Discovery of new molecules with the immunoglobulin superfamily (IgSF) variable (V) domain in amphioxus would help in studying the evolution of IgSF V molecules in the immune system. A protein was found which just contains only one IgSF V domain in amphioxus, termed Amphi-IgSF-V; it has over 30% sequence identity to the V domains of human immunoglobulins and mammalian T-cell receptors. In order to clarify the three-dimensional structure of this new molecule in amphioxus, Amphi-IgSF-V was expressed, purified and crystallized, and diffraction data were collected to a resolution of 1.95 Å. The crystal belonged to space group P3221, with unit-cell parameters a = b = 53.9, c = 135.5 Å. The Matthews coefficient and solvent content were calculated to be 2.58 Å3 Da−1 and 52.38%, respectively. The results will provide structural information to study the evolution of IgSF V molecules in the immune system. PMID:25084385

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

    PubMed

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

    2014-08-01

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

  18. Paradoxical Effect of Nonphysiological Shear Stress on Platelets and von Willebrand Factor.

    PubMed

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

    2016-07-01

    Blood can become hypercoagulable by shear-induced platelet activation and generation of microparticles. It has been reported that nonphysiological shear stress (NPSS) could induce shedding of platelet receptor glycoprotein (GP) Ibα, which may result in an opposite effect to hemostasis. The aim of this study was to investigate the influence of the NPSS on platelets and von Willebrand factor (vWF). Human blood was exposed to two levels of NPSS (25 Pa, 125 Pa) with an exposure time of 0.5 s, generated by using a novel blood-shearing device. Platelet activation (P-selectin expression, GPIIb/IIIa activation and generation of microparticles) and shedding of three platelet receptors (GPIbα, GPVI, GPIIb/IIIa) in sheared blood were quantified using flow cytometry. Aggregation capacity of sheared blood induced by ristocetin and collagen was evaluated using an aggregometer. Shear-induced vWF damage was characterized with Western blotting. Consistent with the published data, the NPSS caused significantly more platelets to become activated with increasing NPSS level. Meanwhile, the NPSS induced the shedding of platelet receptors. The loss of the platelet receptors increased with increasing NPSS level. The aggregation capacity of sheared blood induced by ristocetin and collagen decreased. There was a loss of high molecular weight multimers (HMWMs) of vWF in sheared blood. These results suggest that the NPSS induced a paradoxical effect. More activated platelets increase the risk of thrombosis, while the reduction in platelet receptors and the loss of HMWM-vWF increased the propensity of bleeding. The finding might provide a new perspective to understand thrombosis and acquired bleeding disorder in patients supported with blood contacting medical devices. PMID:26582038

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

    PubMed Central

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

    1988-01-01

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

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

    PubMed

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

    2013-02-01

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

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

    PubMed Central

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

    2013-01-01

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

  2. Mucosal immunoglobulins.

    PubMed

    Woof, Jenny M; Mestecky, Jiri

    2005-08-01

    Due to their vast surface area, the mucosal surfaces of the body represent a major site of potential attack by invading pathogens. The secretions that bathe mucosal surfaces contain significant levels of immunoglobulins (Igs), which play key roles in immune defense of these surfaces. IgA is the predominant antibody class in many external secretions and has many functional attributes, both direct and indirect, that serve to prevent infective agents such as bacteria and viruses from breaching the mucosal barrier. This review details current understanding of the structural and functional characteristics of IgA, including interaction with specific receptors (such as Fc(alpha)RI, Fc(alpha)/microR, and CD71) and presents examples of the means by which certain pathogens circumvent the protective properties of this important Ig. PMID:16048542

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

    PubMed Central

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

    1990-01-01

    Rabbits of the Alicia strain have a mutation (ali) that segregates with the immunoglobulin heavy-chain (lgh) locus and has a cis effect upon the expression of heavy-chain variable-region (VH) genes encoding the a2 allotype. In heterozygous a1/ali or a3/ali rabbits, serum immunoglobulins are almost entirely the products of the normal a1 or a3 allele and only traces of a2 immunoglobulin are detectable. Adult homozygous ali/ali rabbits likewise have normal immunoglobulin levels resulting from increased production of a-negative immunoglobulins and some residual ability to produce the a2 allotype. By contrast, the majority of the immunoglobulins of wild-type a2 rabbits are a2-positive and only a small percentage are a-negative. Genomic DNAs from homozygous mutant and wild-type animals were indistinguishable by Southern analyses using a variety of restriction enzyme digests and lgh probes. However, when digests with infrequently cutting enzymes were analyzed by transverse alternating-field electrophoresis, the ali DNA fragments were 10-15 kilobases smaller than the wild type. These fragments hybridized to probes both for VH and for a region of DNA a few kilobases downstream of the VH genes nearest the joining region. We suggest that this relatively small deletion affects a segment containing 3' VH genes with important regulatory functions, the loss of which leads to the ali phenotype. These results, and the fact that the 3' VH genes rearrange early in B-cell development, indicate that the 3' end of the VH locus probably plays a key role in regulation of VH gene expression. Images PMID:2115171

  4. Intravenous immunoglobulin replacement therapy in common variable immunodeficiency induces B cell depletion through differentiation into apoptosis-prone CD21(low) B cells.

    PubMed

    Mitrevski, Milica; Marrapodi, Ramona; Camponeschi, Alessandro; Lazzeri, Cristina; Todi, Laura; Quinti, Isabella; Fiorilli, Massimo; Visentini, Marcella

    2014-12-01

    Intravenous immunoglobulin (IVIG), besides its use as replacement therapy in patients with antibody deficiencies, is broadly used as an immunomodulatory agent for the treatment of autoimmune and inflammatory disorders. The mechanisms of action of IVIG include Fc receptor blockade, inhibition of cytokines and growth factors, modulation of macrophages and dendritic cells, enhancement of regulatory T cells, and modulation of B cells through the FcγRIIB receptor and CD22. Recent studies suggest that in vitro exposure of human B cells to IVIG determines functional changes reminiscent of anergy and that IVIG treatment of patients with common variable immunodeficiency (CVID) induces in B cells ERK activation, a feature of anergy. Here, we show that IVIG therapy drives the B cells of patients with CVID to down-regulate CD21 expression and to assume the peculiar phenotype of the anergic-like, apoptosis-prone CD21(low) B cells that are spontaneously expanded in a subset of CVID and in some other immunological disorders. The CD21(low) B cells newly generated after IVIG infusion undergo spontaneous apoptosis upon in vitro culture. Furthermore, IVIG infusion is rapidly followed by a significant, although discrete, decrease in the number of circulating B cells, but not of T cells or of natural killer cells. These findings suggest that IVIG therapy may constrain antibody responses by inducing B cell depletion through differentiation into CD21(low) B cells that undergo accelerated apoptosis. PMID:25407649

  5. Intravenous immunoglobulin replacement induces an in vivo reduction of inflammatory monocytes and retains the monocyte ability to respond to bacterial stimulation in patients with common variable immunodeficiencies.

    PubMed

    Cavaliere, Filomena Monica; Prezzo, Alessandro; Conti, Valentina; Bilotta, Caterina; Pulvirenti, Federica; Iacobini, Metello; Quinti, Isabella

    2015-09-01

    Intravenous IgG administration induces significant modifications in the innate and adaptive compartment of the immune system including the monocyte/macrophage system. We analyzed the in vivo effect of IgG administered at replacement dosages on the frequency of monocytes subsets, on the modulation of CD11b and sialic acid-binding immunoglobulin-like lectin receptor (Siglec 9) expression and on monocytes production of reactive oxygen species. We showed that patients with Common Variable Immune Deficiency have an increased frequency pro-inflammatory intermediate CD14(++)CD16(+) monocytes and an increased expression of CD11b and Siglec 9 on monocytes. IgG administered at replacement dosages exerted an in vivo anti-inflammatory effect as shown by a reduction of circulating monocytes, of intermediate pro-inflammatory monocytes, of CD11b and Siglec 9 expression and of ex vivo monocytes oxidative burst. Nevertheless, intravenous IgG administration did not affect the monocyte functional ability to respond to a bacterial stimulation in terms of CD11b and Siglec 9 expression and reactive oxygen species production. PMID:26232049

  6. 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. PMID:23632026

  7. The immunoglobulin heavy-chain variable region in insulin-dependent diabetes mellitus: affected-sib-pair analysis and association studies.

    PubMed Central

    Veijola, R.; Knip, M.; Puukka, R.; Reijonen, H.; Cox, D. W.; Ilonen, J.

    1996-01-01

    We have analyzed immunoglobulin heavy-chain variable-region (VH) polymorphisms and genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) by using a set of polymorphic loci that span approximately 1,000 kb of the VH region on chromosome 14q32. One hundred one Finnish families with at least two children affected with IDDM were studied. Conventional RFLPs determined by hybridization were used, since no microsatellite repeat markers have been available for this gene region. No evidence for linkage between the VH genes and IDDM could be obtained from haplotype-sharing analysis among the 133 diabetic sib pairs. The frequencies of various VH genotypes were also compared between 101 familial IDDM cases and 114 controls derived from the Finnish background population. The distribution of the genotypes at the VH2-B5 locus was significantly different between these groups (P=.004), the 3.4/3.4 genotype being less common in the IDDM cases. In addition, a different genotype distribution at the VH5-B2 locus was observed in the diabetic subjects (P = .022). When the IDDM cases were stratified by presence or absence of the high-risk HLA-DQB1*0302 allele, no differences in VH genotype frequencies were observed between the 0302-positive and 0302-negative cases. In the transmission test for linkage disequilibrium (TDT), no differences were found between the expected and observed frequencies of the transmitted alleles at the VH2-B5 or VH5-B2 locus. In conclusion, significant differences in VH genotype distributions were observed between the familial IDDM cases and the controls, but the observed associations could not be confirmed by the TDT. Haplotype sharing analysis provided no evidence for genetic linkage between the VH gene region and IDDM. Images Figure 1 PMID:8755935

  8. Complete Haplotype Sequence of the Human Immunoglobulin Heavy-Chain Variable, Diversity, and Joining Genes and Characterization of Allelic and Copy-Number Variation

    PubMed Central

    Watson, Corey T.; Steinberg, Karyn M.; Huddleston, John; Warren, Rene L.; Malig, Maika; Schein, Jacqueline; Willsey, A. Jeremy; Joy, Jeffrey B.; Scott, Jamie K.; Graves, Tina A.; Wilson, Richard K.; Holt, Robert A.; Eichler, Evan E.; Breden, Felix

    2013-01-01

    The immunoglobulin heavy-chain locus (IGH) encodes variable (IGHV), diversity (IGHD), joining (IGHJ), and constant (IGHC) genes and is responsible for antibody heavy-chain biosynthesis, which is vital to the adaptive immune response. Programmed V-(D)-J somatic rearrangement and the complex duplicated nature of the locus have impeded attempts to reconcile its genomic organization based on traditional B-lymphocyte derived genetic material. As a result, sequence descriptions of germline variation within IGHV are lacking, haplotype inference using traditional linkage disequilibrium methods has been difficult, and the human genome reference assembly is missing several expressed IGHV genes. By using a hydatidiform mole BAC clone resource, we present the most complete haplotype of IGHV, IGHD, and IGHJ gene regions derived from a single chromosome, representing an alternate assembly of ∼1 Mbp of high-quality finished sequence. From this we add 101 kbp of previously uncharacterized sequence, including functional IGHV genes, and characterize four large germline copy-number variants (CNVs). In addition to this germline reference, we identify and characterize eight CNV-containing haplotypes from a panel of nine diploid genomes of diverse ethnic origin, discovering previously unmapped IGHV genes and an additional 121 kbp of insertion sequence. We genotype four of these CNVs by using PCR in 425 individuals from nine human populations. We find that all four are highly polymorphic and show considerable evidence of stratification (Fst = 0.3–0.5), with the greatest differences observed between African and Asian populations. These CNVs exhibit weak linkage disequilibrium with SNPs from two commercial arrays in most of the populations tested. PMID:23541343

  9. Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up

    PubMed Central

    2012-01-01

    Background Expression of inflammatory cytokines in cerebrospinal fluid (CSF) has led to the hypothesis of intrathecal chronic inflammation to explain the denervation observed in post-polio syndrome (PPS). It has been shown that therapy with intravenous immunoglobulin (IVIG) improves physical performance and dampens down the inflammatory process at 6 months in PPS patients. We here examined the effects of IVIG on cytokine expression and clinical outcome one year after IVIG treatment. Methods From a previous study with 135 PPS patients included, 41 patients were further evaluated before un-blinding for one year (21 placebo and 20 treated with IVIG, Xepol® 50 mg/ml), and were assessed for clinical variables by performing the Short Form-36 survey (SF-36) questionnaire assessment, the 6 minute walk distance test (6MWT) and registering pain level by Visual Analogue Scale (VAS) after IVIG treatment. A separate cohort of 37 PPS patients went through lumbar puncture (LP) at baseline and 20 patients, treated with IVIG, repeated the LP one year later. Thirty patients affected with other neurological diseases (OND) were used as control group. Inflammatory cytokines TNF, TGFβ, IFNγ, IL-23, IL-13 and IL-10 were measured in blood cells and CSF cells with RT-PCR. Results Scores of the physical components of SF-36 were significantly higher at the one year follow up time-point in the IVIG-treated patients when compared to baseline as well as to the control subjects. Pain VAS score and 6MWT improved significantly in the IVIG-treated patients when compared with baseline Relative expression of TNF and IFN-γ in both PBMCs and CSF from PPS patients were increased compared to OND subjects at baseline (p < 0.05). One year after IVIG-treatment a decreased expression of IFN-γ and IL23 was found in CSF of PPS patients, while anti-inflammatory IL-13 was increased (p < 0.05). Conclusions IVIG has effects on relevant QoL variables and inflammatory cytokines up to one year in

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

    PubMed Central

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

    1994-01-01

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

  11. 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.

  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. [The interrelationships between dental parameters and electronic axiographic findings. A study on subjects with nonphysiological incisor relations].

    PubMed

    Schneider, S; Bakopulos, K; Kess, K; Witt, E

    1993-02-01

    The purpose of the present study was to discern possible relationships between dental parameters and the horizontal inclination of the condyle path. Two test groups of orthodontically untreated individuals with non-physiological incisor relationships, one group with enlarged and the other with reverse overjet, were selected for the study. An opto-electronic apparatus was employed to measure the horizontal inclination of the condyle path. The dental parameters were set by clinical examination and by measuring plaster casts. Both groups exhibited significant distribution deviations in the inclination of the condyle path and in the following parameters: "occlusal contacts of the front teeth during protrusion", "overbite", "resulting overjet", and "sagittal and vertical distance of the incisal edge of the lower incisors to the zero point of the upper incisors". Statistically no correlation between the dental parameters and the inclination of the condyle path was discerned. The influence of muscular guidance is in large measure the determining factor for the large variations in the TMJ registrations, and especially in their quantitative evaluation. The results were the same even when tracings were repeated a number of times with the same patient. PMID:8454242

  14. 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

  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. 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. PMID:21276714

  17. Immunoglobulin levels in Iraq.

    PubMed Central

    Al-Agidi, S K; Papiha, S S; Roberts, D F

    1977-01-01

    In a study of immunoglobulin levels in 192 apparently healthy individuals in Iraq, regional differences occur in IgE and IgG. The main levels of IgG, IgM and IgA tend to be low, and of IgE clearly elevated. It is suggested that this pattern may be explained by the presence of intestinal parasites which stimulate IgE production. The genetic differences that exist between the regional populations, and the occurrence of associations of immunoglobulin level with several polymorphic systems, suggests the possibility of a genetic element in the regional immunoglobulin differences. PMID:908174

  18. Non-Physiologic Blood Flow Triggers Endothelial and Arterial Remodeling In Vivo: Implications for Novel LVADs with a Peripheral Anastomosis

    PubMed Central

    Bartoli, Carlo R.; Spence, Paul A.; Siess, Thorsten; Raess, Daniel H.; Koenig, Steven C.; Dowling, Robert D.

    2014-01-01

    Introduction Less-invasive circulatory support devices have been developed that require anastomosis to a peripheral artery. The Symphony Heart Assist System is a volume displacement pump sewn to the subclavian artery to provide partial circulatory support. The surgical configuration produces non-physiologic blood pressure and bidirectional flow in the subclavian artery. Our objective was to identify effects of altered hemodynamics on arterial structure and function. Methods In calves (n=23, 80-100kg), the Symphony pump was sewn end-to-side to the carotid artery. Acutely, carotid blood pressure and flow were recorded to evaluate hemodynamic changes. After medium-term support (1-4 weeks), carotid artery cross sections were studied. Histology and molecular assays evaluated architectural changes. Quantitative real-time PCR evaluated gene expression of matrix metalloproteinase (MMP)-2 and MMP-9 and connective tissue growth factor (CTGF). In vitro carotid arterial-ring studies evaluated physiological responses. Results During Symphony support, carotid arterial pressure was 200/15mmHg. Antegrade flow increased significantly (p<0.05) from 1.40±0.32 to 4.29±0.33L/min. Flow during native cardiac diastole reversed completely from 0.25±0.05 to -4.15±0.38L/min in carotid artery proximal to the anastomosis. After medium-term support, the carotid artery was significantly dilated with significantly thinner tunica media and thicker tunica adventitia versus controls. MMP-9 gene expression decreased significantly, CTGF gene expression increased significantly, and collagen, elastin, and total extracellular matrix increased significantly. Endothelial cells were significantly hypertrophied and produced significantly more von Willebrand factor. Endothelial apoptosis increased significantly. Platelet-endothelial interactions decreased significantly. Endothelial-independent contraction decreased significantly, whereas endothelial-dependant relaxation increased modestly. Conclusions

  19. 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. PMID:26219564

  20. Preparations of intravenous immunoglobulins diminish the number and proinflammatory response of CD14+CD16++ monocytes in common variable immunodeficiency (CVID) patients.

    PubMed

    Siedlar, Maciej; Strach, Magdalena; Bukowska-Strakova, Karolina; Lenart, Marzena; Szaflarska, Anna; Węglarczyk, Kazimierz; Rutkowska, Magdalena; Baj-Krzyworzeka, Monika; Pituch-Noworolska, Anna; Kowalczyk, Danuta; Grodzicki, Tomasz; Ziegler-Heitbrock, Loems; Zembala, Marek

    2011-05-01

    We have studied the effect of intravenous immunoglobulins (IVIG) on monocyte subpopulations and cytokine production in patients with CVID. The absolute number of CD14(+)CD16(++) monocytes decreased on average 2.5-fold 4h after IVIG and after 20h returned to the baseline. The cytokine level in the supernatants of peripheral blood mononuclear cells (PBMC) after ex vivo LPS stimulation demonstrated the >2-fold decrease in TNF production 4h after IVIG. The TNF expression, which is higher in the CD14(+)CD16(++) monocytes, was decreased in these cells by IVIG in 4/7 CVID cases. In vitro exposure of the healthy individuals' monocytes to the IVIG preparation resulted in reduced TNF production, which was overcome by blockade of the FcγRIIB in the CD14(+)CD16(++) CD32B(high) monocytes. Our data suggest that reduction in the number of CD14(+)CD16(++) monocytes and the blockade of their cytokine production via triggering CD32B can contribute to the anti-inflammatory action of IVIG. PMID:21300572

  1. 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. PMID:19883425

  2. 6th International Immunoglobulin Symposium: Poster presentations

    PubMed Central

    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

    2009-01-01

    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 α2,6-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. PMID:19883425

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

    PubMed Central

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

    1989-01-01

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

  4. The Streptococcal Cysteine Protease SpeB Is Not a Natural Immunoglobulin-Cleaving Enzyme

    PubMed Central

    Persson, Helena; Vindebro, Reine

    2013-01-01

    The human bacterial pathogen Streptococcus pyogenes has developed a broad variety of virulence mechanisms to evade the actions of the host immune defense. One of the best-characterized factors is the streptococcal cysteine protease SpeB, an important multifunctional protease that contributes to group A streptococcal pathogenesis in vivo. Among many suggested activities, SpeB has been described to degrade various human plasma proteins, including immunoglobulins (Igs). In this study, we show that SpeB has no Ig-cleaving activity under physiological conditions and that only Igs in a reduced state, i.e., semimonomeric molecules, are cleaved and degraded by SpeB. Since reducing conditions outside eukaryotic cells have to be considered nonphysiological and IgG in a reduced state lacks biological effector functions, we conclude that SpeB does not contribute to S. pyogenes virulence through the proteolytic degradation of Igs. PMID:23569114

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

    PubMed Central

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

    2014-01-01

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

  6. [Immunoglobulin deficiency after repeated plasmapheresis].

    PubMed

    Stebler, C; Tichelli, A; Dazzi, H; Wernli, M; Gratwohl, A; Speck, B

    1991-02-01

    In 10 patients with Guillain-Barré syndrome the level of globulins and immunoglobulins before and after plasmapheresis was investigated. As a plasma substitute either PPL (in 8 patients) or a plasma substitute solution rich in immunoglobulins (in 2 patients) was used. When plasma was substituted with PPL, the globulins and immunoglobulins dropped to a mean of 40% of the initial value (range 30-60%) after the first plasmapheresis. With daily or alternate day plasmapheresis, the globulins only partially recovered. Before the second plasmapheresis they were still reduced to a mean of 50% (range 20-50%), and dropped further with ongoing exchanges to a mean of 33% (range 20-50%) as measured before the third plasmapheresis. Accordingly, there was a loss of immunoglobulins of similar magnitude. With the use of a plasma substitute solution rich in immunoglobulins (IRP), globulins could be maintained at normal levels. The lowest immunoglobulin values measured after plasmapheresis were 6 g/l (normal range 8-17 g/l). One patient developed gram-negative septicaemia after plasmapheresis with PPL, possibly due to a low immunoglobulin concentration. We conclude that a plasma substitute solution rich in immunoglobulins should be used for therapeutic plasmapheresis in order to maintain physiological immunoglobulin concentrations. PMID:2003210

  7. Biology of Immunoglobulins

    PubMed Central

    Berlot, Giorgio; Rossini, Perla; Turchet, Federica

    2015-01-01

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

  8. Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells

    PubMed Central

    Klein, Ulf; Rajewsky, Klaus; Küppers, Ralf

    1998-01-01

    Immunoglobulin (Ig)M+IgD+ B cells are generally assumed to represent antigen-inexperienced, naive B cells expressing variable (V) region genes without somatic mutations. We report here that human IgM+IgD+ peripheral blood (PB) B cells expressing the CD27 cell surface antigen carry mutated V genes, in contrast to CD27-negative IgM+IgD+ B cells. IgM+IgD+CD27+ B cells resemble class-switched and IgM-only memory cells in terms of cell phenotype, and comprise ∼15% of PB B lymphocytes in healthy adults. Moreover, a very small population (<1% of PB B cells) of highly mutated IgD-only B cells was detected, which likely represent the PB counterpart of IgD-only tonsillar germinal center and plasma cells. Overall, the B cell pool in the PB of adults consists of ∼40% mutated memory B cells and 60% unmutated, naive IgD+CD27− B cells (including CD5+ B cells). In the somatically mutated B cells, VH region genes carry a two- to threefold higher load of somatic mutation than rearranged Vκ genes. This might be due to an intrinsically lower mutation rate in κ light chain genes compared with heavy chain genes and/or result from κ light chain gene rearrangements in GC B cells. A common feature of the somatically mutated B cell subsets is the expression of the CD27 cell surface antigen which therefore may represent a general marker for memory B cells in humans. PMID:9802980

  9. The Major Phase-Variable Outer Membrane Protein of Escherichia coli Structurally Resembles the Immunoglobulin A1 Protease Class of Exported Protein and Is Regulated by a Novel Mechanism Involving Dam and OxyR

    PubMed Central

    Henderson, Ian R.; Owen, Peter

    1999-01-01

    Here we report the characterization of an Escherichia coli gene (agn43) which encodes the principal phase-variable outer membrane protein termed antigen 43 (Ag43). The agn43 gene encodes a precursor protein of 107 kDa containing a 52-amino-acid signal sequence. Posttranslational processing generates an α43 subunit (predicted Mr of 49,789) and a C-terminal domain (β43) with features typical of a bacterial integral outer membrane protein (predicted Mr of 51,642). Secondary structure analysis predicts that β43 exists as an 18-stranded β barrel and that Ag43 shows structural organization closely resembling that of immunoglobulin A1 protease type of exoprotein produced by pathogenic Neisseria and Haemophilus spp. The correct processing of the polyprotein to α43 and β43 in OmpT, OmpP, and DegP protease-deficient E. coli strains points to an autocatalytic cleavage mechanism, a hypothesis supported by the occurrence of an aspartyl protease active site within α43. Ag43, a species-specific antigen, possesses two RGD motifs of the type implicated in binding to human integrins. The mechanism of reversible phase variation was studied by immunochemical analysis of a panel of well-defined regulatory mutants and by analysis of DNA sequences upstream of agn43. Evidence strongly suggests that phase variation is regulated by both deoxyadenosine methylase (Dam) and by OxyR. Thus, oxyR mutants are locked on for Ag43 expression, whereas dam mutants are locked off for Ag43 expression. We propose a novel mechanism for the regulation of phase switching in which OxyR competes with Dam for unmethylated GATC sites in the regulatory region of the agn43 gene. PMID:10094691

  10. Blood Test: Immunoglobulin A (IgA)

    MedlinePlus

    ... Melon Smoothie Pregnant? Your Baby's Growth Blood Test: Immunoglobulin A (IgA) KidsHealth > For Parents > Blood Test: Immunoglobulin ... of immunoglobulin A, one of the most common antibodies in the body. Antibodies are proteins made by ...

  11. Update on the hyper immunoglobulin M syndromes

    PubMed Central

    Davies, E Graham; Thrasher, Adrian J

    2010-01-01

    The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination (CSR), with or without defects of somatic hypermutation (SHM). They can be classified as defects of signalling through CD40 causing both a humoral immunodeficiency and a susceptibility to opportunistic infections, or intrinsic defects in B cells of the mechanism of CSR resulting in a pure humoral immunodeficiency. A HIGM picture can also be seen as part of generalized defects of DNA repair and in antibody deficiency syndromes, such as common variable immunodeficiency. CD40 signalling defects may require corrective therapy with bone marrow transplantation. Gene therapy, a potential curative approach in the future, currently remains a distant prospect. Those with a defective CSR mechanism generally do well on immunologoblulin replacement therapy. Complications may include autoimmunity, lymphoid hyperplasia and, in some cases, a predisposition to lymphoid malignancy. PMID:20180797

  12. Immunoglobulin profile in schizophrenia.

    PubMed

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

    1992-08-01

    The present study was conducted on 40 new consecutive schizophrenic patients admitted in the psychiatry ward. The diagnosis of schizophrenia was done by Research Diagnosis Criteria (RDC). Serum immunoglobulins were were estimated in schizophrenic patients and were age and sex matched with 40 healthy individuals, comprising the control group. The IgG and IgA mean levels of schizophrenic patients were found to be significantly higher (p < 0.01) than the normal healthy individuals. There were however no significant differences between the schizophrenic patients and control group regarding total proteins, albumin and globulin levels. In subtypes of schinophrenia based on phenomenology only, paranoid group scored significantly higher (p < 0.01) IgG and IgA mean values than other types of Schizophrenia (catatonic, disorganised and undifferentiated). PMID:1473841

  13. Immunoglobulin Resistance in Kawasaki Disease

    PubMed Central

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

    2015-01-01

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

  14. Immunoglobulin levels in infantile pneumocystosis

    PubMed Central

    Kohout, Elfriede; Post, Cornelius; Azadeh, Bahram; Dutz, Werner; Bandarizadeh, Bashi; Kadivar, Darius

    1972-01-01

    Two hundred and twelve determinations of IgA, IgG, and IgM were performed in 50 infants during an epidemic of interstitial plasma cell pneumonia. Criteria for diagnosis are discussed. The immunoglobulin levels in pneumocystic, non-pneumocystic, and normal American infants are compared. An analysis of the findings in individual cases reveals a time-related immunoglobulin response, which helps to elucidate the pathogenicity of the disease. PMID:4536973

  15. Unusual monoclonal DNA binding immunoglobulin.

    PubMed

    Sawada, S; Iijima, S; Kuwana, K; Nishinarita, S; Takeuchi, J; Shida, M; Karasaki, M; Amaki, I

    1983-03-01

    The monoclonal antibodies directed against DNA were produced by somatic cell hybridization with parental cells (SP-2) and spleen cells from nonimmunized autoimmune MRL/lpr mice. The immunoglobulins were recovered from the culture supernatant from hybridoma by a solid immunoadsorbent and antibody immunoprecipitation. The results from the specificities of DNA binding monoclonal immunoglobulins suggest that the antibodies to DNA have the antibody combining sites for both epitope of double stranded helix and base of DNA and support the concept of the multiple antigen binding potentials of the hybridoma autoantibodies. PMID:6857646

  16. 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. PMID:26853951

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

    PubMed Central

    2013-01-01

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

  18. Human immunoglobulin allotypes

    PubMed Central

    Lefranc, Marie-Paule

    2009-01-01

    More than twenty recombinant monoclonal antibodies are approved as therapeutics. Almost all of these are based on the whole IgG isotype format, but vary in the origin of the variable regions between mouse (chimeric), humanized mouse and fully human sequences; all of those with whole IgG format employ human constant region sequences. Currently, the opposing merits of the four IgG subclasses are considered with respect to the in vivo biological activities considered to be appropriate to the disease indication being treated. Human heavy chain genes also exhibit extensive structural polymorphism(s) and, being closely linked, are inherited as a haplotype. Polymorphisms (allotypes) within the IgG isotype were originally discovered and described using serological reagents derived from humans; demonstrating that allotypic variants can be immunogenic and provoke antibody responses as a result of allo-immunization. The serologically defined allotypes differ widely within and between population groups; therefore, a mAb of a given allotype will, inevitably, be delivered to a cohort of patients homozygous for the alternative allotype. This publication reviews the serologically defined human IgG allotypes and considers the potential for allotype differences to contribute to or potentiate immunogenicity. PMID:20073133

  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. PMID:26921669

  20. 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. PMID:25761372

  1. Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR.

    PubMed

    Ritgen, Matthias; Stilgenbauer, Stephan; von Neuhoff, Nils; Humpe, Andreas; Brüggemann, Monika; Pott, Christiane; Raff, Thorsten; Kröber, Alexander; Bunjes, Donald; Schlenk, Richard; Schmitz, Norbert; Döhner, Hartmut; Kneba, Michael; Dreger, Peter

    2004-10-15

    The aim of this study was to investigate if graft-versus-leukemia (GVL) activity conferred by allogeneic stem cell transplantation (allo-SCT) is effective in chronic lymphocytic leukemia (CLL) with unmutated V(H) gene status. The kinetics of residual disease (MRD) were measured by quantitative allele-specific immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) in 9 patients after nonmyeloablative allo-SCT for unmutated CLL. Despite an only modest decrease in the early posttransplantation phase, MRD became undetectable in 7 of 9 patients (78%) from day +100 onwards subsequent to chronic graft-versus-host disease or donor lymphocyte infusions. With a median follow-up of 25 months (range, 14-37 months), these 7 patients remain in continuous clinical and molecular remission. In contrast, PCR negativity was achieved in only 6 of 26 control patients (23%) after autologous SCT for unmutated CLL and it was not durable. Taken together, this study shows for the first time that GVL-mediated immunotherapy might be effective in CLL with unmutated V(H). PMID:15205268

  2. [Intravenous and subcutaneous immunoglobulin therapy].

    PubMed

    Thon, Vojtěch

    2013-07-01

    Patients with agammaglobulinaemia and hypogammaglobulinaemia require immunoglobulin G (IgG) replacement therapy to prevent serious infections. Since the 1950s, therapy with human immune globulin products has been the standard of treatment. Currently, the most common routes of administration of IgG replacement therapy are intravenous (IVIG) or subcutaneous (SCIG). The home therapy may improve the quality of life in patients who require lifelong IgG replacement. The -anti-IgA antibody test identifies the patients with the risk of anaphylactoid reactions in IVIG replacement. The SCIG delivery may be used in patients with anti-IgA antibodies and previous systemic reactions to IVIG. PMID:23964967

  3. Subcutaneous immunoglobulin: opportunities and outlook

    PubMed Central

    Misbah, S; Sturzenegger, M H; Borte, M; Shapiro, R S; Wasserman, R L; Berger, M; Ochs, H D

    2009-01-01

    Immunoglobulin (Ig) administration via the subcutaneous (s.c.) route has become increasingly popular in recent years. The method does not require venous access, is associated with few systemic side effects and has been reported to improve patients' quality of life. One current limitation to its use is the large volumes which need to be administered. Due to the inability of tissue to accept such large volumes, frequent administration at multiple sites is necessary. Most studies conducted to date have investigated the use of subcutaneous immunoglobulin (SCIg) in patients treated previously with the intravenous (i.v.) formulation. New data now support the use of s.c. administration in previously untreated patients with primary immunodeficiencies. SCIg treatment may further be beneficial in the treatment of autoimmune neurological conditions, such as multi-focal motor neuropathy; however, controlled trials directly comparing the s.c. and i.v. routes are still to be performed for this indication. New developments may further improve and facilitate the s.c. administration route. For example, hyaluronidase-facilitated administration increases the bioavailability of SCIg, and may allow for the administration of larger volumes at a single site. Alternatively, more concentrated formulations may reduce the volume required for administration, and a rapid-push technique may allow for shorter administration times. As these developments translate into clinical practice, more physicians and patients may choose the s.c. administration route in the future. PMID:19883424

  4. Subcutaneous immunoglobulin replacement therapy: ensuring success.

    PubMed

    Younger, M Elizabeth M; Blouin, William; Duff, Carla; Epland, Kristin Buehler; Murphy, Elyse; Sedlak, Debra

    2015-01-01

    Subcutaneous immunoglobulin (SCIg) infusions are an option for patients requiring immunoglobulin therapy. Nurses are uniquely positioned to advocate for patients and to teach them how to successfully manage their infusions. The purpose of this review is to describe SCIg therapy and to provide teaching instructions as well as creative tips to ensure treatment success. PMID:25545976

  5. 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. PMID:19670998

  6. Induction of polyclonal immunoglobulin synthesis.

    PubMed

    James, S P

    2001-05-01

    This unit is designed to examine the effects of T cells or lymphokines on B cell differentiation in situations where the antigen specificity of the B cells is not of interest. In these cases, antibody production induced by polyclonal stimuli (e.g., mitogens, antibodies, Epstein-Barr virus (EBV), or lymphokines) can be measured instead of antigen-specific immunoglobulin production. Because B cells in the circulation and tissues are pleomorphic (containing subpopulations of cells that may be resting, cells that may have had prior antigenic exposure, and cells that may have undergone prior isotype commitment), the antibody responses of these subpopulations to various growth and differentiation factors differ. Therefore, the choice of which lymphocyte subpopulation to culture and which activation signal to use is determined by the particular experimental question. PMID:18432825

  7. Destabilizing loop swaps in the CDRs of an immunoglobulin VL domain.

    PubMed Central

    Helms, L. R.; Wetzel, R.

    1995-01-01

    It is generally believed that loop regions in globular proteins, and particularly hypervariable loops in immunoglobulins, can accommodate a wide variety of sequence changes without jeopardizing protein structure or stability. We show here, however, that novel sequences introduced within complementarity determining regions (CDRs) 1 and 3 of the immunoglobulin variable domain REI VL can significantly diminish the stability of the native state of this protein. Besides their implications for the general role of loops in the stability of globular proteins, these results suggest previously unrecognized stability constraints on the variability of CDRs that may impact efforts to engineer new and improved activities into antibodies. PMID:8535243

  8. 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

  9. 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

  10. Influence of Intravenous Immunoglobulin Treatment on Thrombopoiesis.

    PubMed

    Meyer, Oliver; Winter, Oliver; Salama, Abdulgabar

    2012-06-01

    AIM: The mechanisms by which intravenous immunoglobulins (IVIg) result in an increase in platelet counts in most patients with autoimmune thrombocytopenia (ITP) have not yet been fully explained. One of these mechanisms may be related to stimulation of thrombopoiesis. METHODS: A total of 13 adult patients who received IVIg were studied: 11 patients with primary ITP, 1 patient with ITP related to common variable immunodeficiency (CVID), and 1 patient with uncharacterized thrombocytopenia. IVIg (0.5-1.5 g/kg body weight) was administered on consecutive days (days 1-3). Endogenous thrombopoietin (eTPO) was measured prior to and at least 1 day following treatment. In addition, IL-6 was measured in 5 of the treated patients. RESULTS: In 10 of 13 patients, IVIg treatment resulted in an increase in platelet counts. eTPO remained unchanged or elevated in almost all cases where the platelet count remained low (<100 × 10(3)/μ0. In all cases with normal or increased platelet counts (>100 × 10(3)/μ0, the eTPO concentration decreased. Furthermore, IVIg induced IL-6 synthesis in all 5 examined patients. CONCLUSION: Our data indicate that the induction of eTPO synthesis by IL-6 may be a potential mechanism in which IVIg may stimulate thrombopoiesis. Further studies are required to characterize this mechanism. PMID:22851938

  11. 7th International Immunoglobulin Conference: Immunodeficiencies.

    PubMed

    Schmidt, R E; Ochs, H D

    2014-12-01

    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

  12. General mechanism for modulating immunoglobulin effector function

    PubMed Central

    Sondermann, Peter; Pincetic, Andrew; Maamary, Jad; Lammens, Katja; Ravetch, Jeffrey V.

    2013-01-01

    Immunoglobulins recognize and clear microbial pathogens and toxins through the coupling of variable region specificity to Fc-triggered cellular activation. These proinflammatory activities are regulated, thus avoiding the pathogenic sequelae of uncontrolled inflammation by modulating the composition of the Fc-linked glycan. Upon sialylation, the affinities for Fcγ receptors are reduced, whereas those for alternative cellular receptors, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)/CD23, are increased. We demonstrate that sialylation induces significant structural alterations in the Cγ2 domain and propose a model that explains the observed changes in ligand specificity and biological activity. By analogy to related complexes formed by IgE and its evolutionarily related Fc receptors, we conclude that this mechanism is general for the modulation of antibody-triggered immune responses, characterized by a shift between an “open” activating conformation and a “closed” anti-inflammatory state of antibody Fc fragments. This common mechanism has been targeted by pathogens to avoid host defense and offers targets for therapeutic intervention in allergic and autoimmune disorders. PMID:23697368

  13. Shared epitopes of avian immunoglobulin light chains.

    PubMed

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

    2014-04-15

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

  14. Random yet deterministic: convergent immunoglobulin responses to influenza

    PubMed Central

    Martins, Andrew; Tsang, John S.

    2014-01-01

    B-cell clonal expansion is a hallmark of host-defense and vaccination responses. Given the vast immunoglobulin repertoire, individuals may expand B cells carrying largely distinct immunoglobulin genes following antigenic challenge. Using immunoglobulin-repertoire sequencing to dynamically track responses to influenza vaccination, Jackson et al. find evidence of convergent immunoglobulin responses across individuals. PMID:25179798

  15. Recognition of additional roles for immunoglobulin domains in immune function

    PubMed Central

    Cannon, John P.; Dishaw, Larry J.; Haire, Robert N.; Litman, Ronda T.; Ostrov, David A.; Litman, Gary W.

    2010-01-01

    Characterization of immune receptors found in phylogenetically disparate species at the genetic, structural and functional levels has provided unique insight into the evolutionary acquisition of immune function. The roles of variable- and intermediate-type immunoglobulin (Ig) domains in direct recognition of ligands and other functions are far wider than previously anticipated. Common mechanisms of multigene family diversification and expansion as well as unique adaptations that relate to function continue to provide unique insight into the numerous patterns, processes and complex interactions that regulate the host response to infectious challenge. PMID:20004115

  16. Subcutaneous Immunoglobulin in Refractory Juvenile Dermatomyositis.

    PubMed

    de Inocencio, Jaime; Enríquez-Merayo, Eugenia; Casado, Rocío; González-Granado, Luis Ignacio

    2016-04-01

    Juvenile dermatomyositis (JDM) is the most common form of juvenile idiopathic inflammatory myopathy. We report a child with steroid-dependent JDM refractory to hydroxychloroquine and subcutaneous methotrexate who experienced systemic reactions to intravenous immunoglobulin and was successfully treated with subcutaneous immunoglobulin. This form of therapy has been shown to be safe, has a very low rate of adverse effects, does not require hospital admission, reduces the number of missed school days, and decreases the costs associated with treatment. PMID:26966131

  17. Immunoglobulin light chain variable region gene sequences for human antibodies to Haemophilus influenzae type b capsular polysaccharide are dominated by a limited number of V kappa and V lambda segments and VJ combinations.

    PubMed Central

    Adderson, E E; Shackelford, P G; Insel, R A; Quinn, A; Wilson, P M; Carroll, W L

    1992-01-01

    The immune repertoire to Haemophilus influenzae type b capsular polysaccharide (Hib PS) appears to be dominated by certain light chain variable region genes (IgVL). In order to examine the molecular basis underlying light chain bias, IgVL genes have been cloned from a panel of heterohybridomas secreting human anti-Hib PS (antibody) (anti-Hib PS Ab). One hybridoma, representative of the predominant serum clonotype of anti-Hib PS Ab in older children and adults following immunization or Hib infection, uses a V kappa II segment identical to the germline gene A2, and a JK3 segment. A second kappa hybridoma uses a member of the V kappa I family and a JK4 segment. Four lambda antibodies, all cross-reactive with the structurally related antigen Escherichia coli K100 PS, use V lambda VII segments which are 96-98% homologous to one another, and may originate from a single germline gene. Two additional lambda antibodies, not K100-cross-reactive, are encoded by members of the V lambda II family. All lambda antibodies use highly homologous J lambda 2 or J lambda 3 segments. The VJ joints of all lambda antibodies and the V kappa II-encoded antibody are notable for the presence of an arginine codon, suggesting an important role in antigen binding. Although more complex than heavy chain variable region gene usage, a significant portion of serum anti-Hib PS Ab is likely to be encoded by a limited number of V kappa and V lambda segments and VJ combinations, which may be selectively expressed during development, or following antigen exposure. Images PMID:1541667

  18. Detecting selection in immunoglobulin sequences.

    PubMed

    Uduman, Mohamed; Yaari, Gur; Hershberg, Uri; Stern, Jacob A; Shlomchik, Mark J; Kleinstein, Steven H

    2011-07-01

    The ability to detect selection by analyzing mutation patterns in experimentally derived immunoglobulin (Ig) sequences is a critical part of many studies. Such techniques are useful not only for understanding the response to pathogens, but also to determine the role of antigen-driven selection in autoimmunity, B cell cancers and the diversification of pre-immune repertoires in certain species. Despite its importance, quantifying selection in experimentally derived sequences is fraught with difficulties. The necessary parameters for statistical tests (such as the expected frequency of replacement mutations in the absence of selection) are non-trivial to calculate, and results are not easily interpretable when analyzing more than a handful of sequences. We have developed a web server that implements our previously proposed Focused binomial test for detecting selection. Several features are integrated into the web site in order to facilitate analysis, including V(D)J germline segment identification with IMGT alignment, batch submission of sequences and integration of additional test statistics proposed by other groups. We also implement a Z-score-based statistic that increases the power of detecting selection while maintaining specificity, and further allows for the combined analysis of sequences from different germlines. The tool is freely available at http://clip.med.yale.edu/selection. PMID:21665923

  19. Cytomegalovirus Immunoglobulin After Thoracic Transplantation

    PubMed Central

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

    2016-01-01

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

  20. [Immunoglobulin for prevention of radiogenic mucositis].

    PubMed

    Mose, S; Adamietz, I A; Thilmann, C; Saran, F; Heyd, R; Knecht, R; Böttcher, H D

    1995-07-01

    Among various therapies administered during radiation-induced mucositis, treatment with immunoglobulin has proven clinically successful. In this study the efficacy of prophylactic applications of immunoglobulin was investigated from January 1992 through August 1993. Forty-two patients with histologically-proven head and neck cancer were given postoperative radiation treatment. In cases with macroscopic tumor residues or inoperability, combined radio-chemotherapy was given. This included 51.3 Gy at 1.9 Gy 5x/week, boosted to 10-26 Gy at 2 Gy 5x/week and carboplatin 60 mg/m2 at days 1-5 and 29-33. Panthenol (4x10 ml/day) and nystatin (4 x 1 ml/day) were given to 20 patients as prophylactic treatment for mucositis. Twenty-two subsequent patients also received intramuscular 800 mg (5 ml) human immunoglobulin (1x/week). According to the Seegenschmiedt/Sauer classification the extent of mucositis was determined 3x/week. Comparison of the distribution of maximal mucositis revealed a slightly more severe mucosal reaction in the control group (n.s.). Analysis of the mean degree of mucositis in both groups demonstrated statistically significant differences (p = 0.031) related to the whole collective and patients receiving concomitant chemotherapy while no effect of immunoglobulin was found in patients treated by radiation alone. In the immunoglobulin-treated-group, the time from the beginning of therapy to the first interruption was prolonged 5 days (37.5 +/- 13.1 vs. 42.7 +/- 13.3 days), but this difference was not significant. Although prophylactic application of immunoglobulin seemed to lower the degree of radiation-induced mucositis, this effect was less significant when compared to the immunoglobulin given in a therapeutic manner. PMID:7672999

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

    NASA Astrophysics Data System (ADS)

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

    1980-09-01

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

  2. X-linked Agammaglobulinemia With Normal Immunoglobulin and Near-Normal Vaccine Seroconversion.

    PubMed

    Preece, Kahn; Lear, Graeme

    2015-12-01

    We present a 22-month-old boy with X-linked agammaglobulinemia masked by normal immunoglobulin levels and vaccine seroconversion. Diagnosis was made after strong clinical suspicion of immune deficiency led to identification of markedly reduced B-cell numbers and confirmation with identification of a novel Bruton tyrosine kinase gene mutation. He was commenced on replacement immunoglobulin therapy with excellent clinical improvement. This case highlights the variability of phenotypic presentation and apparent disunity between routine immunologic investigations and severe disease in X-linked agammaglobulinemia, necessitating clinical acumen to make the diagnosis. PMID:26527549

  3. Using bioinformatics tools for the sequence analysis of immunoglobulins and T cell receptors.

    PubMed

    Lefranc, Marie-Paule

    2006-03-01

    The huge potential repertoire of 10(12) immunoglobulins and 10(12) T cell receptors per individual results from complex mechanisms of combinatorial diversity between the variable (V), diversity (D), and junction (J) genes, nucleotide deletions and insertions (N-diversity) at the junctions and, for the immunoglobulins, somatic hypermutations. The accurate analysis of rearranged immunoglobulin and T cell receptor sequences, and the annotation of the junctions, therefore represent a huge challenge. The IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts, were the prerequisites for the implementation of the IMGT/V-QUEST and IMGT/JunctionAnalysis tools. IMGT/V-QUEST analyzes germline V and rearranged V-J or V-D-J nucleotide sequences. IMGT/JunctionAnalysis is the first tool that automatically analyzes the complex junctions in detail. These interactive tools are easy to use and freely available on the Web (http://imgt.cines.fr), either separately or integrated. PMID:18432961

  4. Enhancement of Polymeric Immunoglobulin Receptor Transcytosis by Biparatopic VHH

    PubMed Central

    Emmerson, Chris D.; van der Vlist, Els J.; Braam, Myrthe R.; Vanlandschoot, Peter; Merchiers, Pascal; de Haard, Hans J. W.; Verrips, C. Theo; van Bergen en Henegouwen, Paul M. P.; Dolk, Edward

    2011-01-01

    The polymeric immunoglobulin receptor (pIgR) ensures the transport of dimeric immunoglobulin A (dIgA) and pentameric immunoglobulin M (pIgM) across epithelia to the mucosal layer of for example the intestines and the lungs via transcytosis. Per day the human pIgR mediates the excretion of 2 to 5 grams of dIgA into the mucosa of luminal organs. This system could prove useful for therapies aiming at excretion of compounds into the mucosa. Here we investigated the use of the variable domain of camelid derived heavy chain only antibodies, also known as VHHs or Nanobodies®, targeting the human pIgR, as a transport system across epithelial cells. We show that VHHs directed against the human pIgR are able to bind the receptor with high affinity (∼1 nM) and that they compete with the natural ligand, dIgA. In a transcytosis assay both native and phage-bound VHH were only able to get across polarized MDCK cells that express the human pIgR gene in a basolateral to apical fashion. Indicating that the VHHs are able to translocate across epithelia and to take along large particles of cargo. Furthermore, by making multivalent VHHs we were able to enhance the transport of the compounds both in a MDCK-hpIgR and Caco-2 cell system, probably by inducing receptor clustering. These results show that VHHs can be used as a carrier system to exploit the human pIgR transcytotic system and that multivalent compounds are able to significantly enhance the transport across epithelial monolayers. PMID:22022593

  5. 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.

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

    PubMed Central

    Frisch-Niggemeyer, W

    1975-01-01

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

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

    PubMed

    Leslie, G A; Clem, L W

    1969-12-01

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

  8. 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. PMID:16663455

  9. Nonphysiological Binding of Ethylene by Plants

    PubMed Central

    Abeles, Fred B.

    1984-01-01

    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 CO2 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. PMID:16663455

  10. The disulphide bridges of a mouse immunoglobulin G1 protein

    PubMed Central

    Svasti, J.; Milstein, C.

    1972-01-01

    [35S]Cystine-labelled immunoglobulin MOPC21 (IgG1) was prepared from myeloma cells in tissue culture. Carrier myeloma protein was added and the protein was digested with pepsin. The digest was fractionated on Sephadex G-50 into two fractions, further digested with trypsin and again fractionated on Sephadex. Disulphide-bridge peptides were purified by electrophoresis and chromatography and identified by radioautography. A peptide of 96 residues was isolated, which contains both the heavy–light interchain disulphide bridge and all the inter-heavy-chain disulphide bridges. Other peptides were isolated, accounting for all the intrachain disulphide bridges (which could be placed by homology with proteins of other species), except for the variable section of the light chain. Sequences describing this missing disulphide bridge were obtained from totally reduced and alkylated light chains. Peptides related to the interchain disulphide-bridge peptide were isolated from partially reduced and alkylated myeloma protein and from totally reduced heavy chain. The interchain disulphide-bridge peptide was placed at the C-terminal position of the F(ab′)2 fragment, prepared by digestion of the protein with pepsin at pH4.0. Sequences from the heavy-chain intrachain disulphide bridges of MOPC 21 immunoglobulin are compared with homologous sequences from mouse myeloma proteins of other subclasses and proteins of other species. PMID:5073237

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

    SciTech Connect

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

    1991-01-01

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

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

    SciTech Connect

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

    1991-12-31

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

  14. Bactericidal properties of Campylobacter jejuni-specific immunoglobulin M antibodies in commercial immunoglobulin preparations.

    PubMed Central

    Autenrieth, I B; Schwarzkopf, A; Ewald, J H; Karch, H; Lissner, R

    1995-01-01

    Campylobacter jejuni is one of the most common enterocolitis-causing microorganisms worldwide. It is of particular importance in immunodeficient patients, who frequently are prone to develop extraintestinal manifestations. Since these cases respond poorly to antibiotic treatment, a supportive immunomodulating therapy including the administration of C. jejuni-specific immunoglobulins would be desirable. In the present study, nine commercial immunoglobulin preparations for intravenous use were tested for the presence of C. jejuni lipopolysaccharide (LPS)- and outer membrane protein (OMP)-specific antibodies by using immunoblot and enzyme-linked immunosorbent assay techniques. The immunoglobulin G (IgG) antibody reactivities against these antigens were comparable in eight of nine tested immunoglobulin preparations. Only in one preparation were C. jejuni OMP- and LPS-specific IgM antibodies found. In this preparation the immunoblot test revealed a strong reactivity against both flagellin and a major OMP. Moreover, all immunoglobulin preparations recognized OMPs of C. jejuni serotypes Lior 4, 9, 11, and 29 equally strongly, while the reactivity to an anti-Lior 36 isolate was less marked. Furthermore, the bactericidal properties of three immunoglobulin preparations were tested by means of chemiluminescence signaling in and bacterial killing by human polymorphonuclear leukocytes (PMNL). The results show that the IgM preparation enhanced Campylobacter-triggered chemiluminescence signaling in PMNL as well as killing of C. jejuni by PMNL, while the other immunoglobulin preparations did not do so. These results suggest that the administration of immunoglobulin preparations containing C. jejuni-specific IgM antibodies would be beneficial for patients with severe C. jejuni infections. PMID:8540699

  15. Proliferative glomerulonephritis with monoclonal immunoglobulin in renal allografts

    PubMed Central

    Al-Rabadi, Laith; Francis, Jean M.; Henderson, Joel; Ghai, Sandeep

    2015-01-01

    Glomerulopathy due to dysproteinemia can have a wide spectrum of pathologic and clinical features based on specific characteristics of the abnormal protein and the response induced within the parenchymal tissue. Monoclonal immunoglobulin G (IgG) deposition can manifest as a different glomerular disease. Proliferative glomerulonephritis (GN) with monoclonal IgG deposits (PGNMID) is a unique entity mimicking immune complex GN that does not conform to any of those subtypes. IgG monoclonal granular deposition in the glomeruli with a pattern similar to immune complex disease suggested by C3 and C1q deposition should prompt consideration of PGNMID. Literature is scarce in terms of recurrence of disease in renal allografts. In this article we present the clinical–pathologic features of three cases of PGNMID in the renal allograft showing the variable course and manifestation of the disease. PMID:26613031

  16. Explanatory style and Immunoglobulin A (IgA).

    PubMed

    Brennan, F X; Charnetski, C J

    2000-01-01

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

  17. Role of immunoglobulins in neonatal sepsis

    PubMed Central

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

    2015-01-01

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

  18. The function of immunoglobulin A in immunity.

    PubMed

    Woof, Jenny M; Kerr, Michael A

    2006-01-01

    The vast surfaces of the gastrointestinal, respiratory, and genitourinary tracts represent major sites of potential attack by invading micro-organisms. Immunoglobulin A (IgA), as the principal antibody class in the secretions that bathe these mucosal surfaces, acts as an important first line of defence. IgA, also an important serum immunoglobulin, mediates a variety of protective functions through interaction with specific receptors and immune mediators. The importance of such protection is underlined by the fact that certain pathogens have evolved mechanisms to compromise IgA-mediated defence, providing an opportunity for more effective invasion. IgA function may also be perturbed in certain disease states, some of which are characterized by deposition of IgA in specific tissues. This review details current understanding of the roles played by IgA in both health and disease. PMID:16362985

  19. [High-dose intravenous immunoglobulin treatment].

    PubMed

    Taneichi, Hiromichi; Miyawaki, Toshio

    2011-03-01

    Intravenous immunoglobulin treatment was introduced as replacement therapy for patients with congenital agammaglobulinemia. For the last three decades, high-dose intravenous immunoglobulin (HD-IVIg) has been used for autoimmune diseases and systemic inflammatory diseases, such as idiopathic thrombocytopenic purpura, Kawasaki disease, myasthenia gravis and Guillain-Barré/syndrome. Although the immunomodulatory mechanisms of HD-IVIg remains unclear. Its use in many other diseases have been expected. Acute encephalitis/encephalopathy is a complex neurological syndrome associated with significant morbidity and mortality. The pathogenicity of brain dysfunction is still unknown. This review provides an overview and discussion of mechanisms that may be responsible for HD-IVIg effects in acute encephalitis/encephalopathy. PMID:21400848

  20. Neuromyelitis optica: potential roles for intravenous immunoglobulin.

    PubMed

    Wingerchuk, Dean M

    2013-01-01

    Neuromyelitis optica (NMO) is an idiopathic central nervous system inflammatory demyelinating disease that causes optic neuritis, transverse myelitis, and other CNS syndromes. It is distinct from multiple sclerosis and is associated with autoantibodies that target aquaporin-4 (AQP4), an astrocyte water channel. Evidence indicating antibody-mediated immune injury in NMO includes its association with other autoimmune diseases, lesional pathology that reveals prominent complement activation and immunoglobulin deposition, pathogenic potential of AQP4 autoantibodies based on in vitro studies, and reports of putative animal models of the disease. The rationale and potential role for intravenous immunoglobulin in NMO will be discussed in the context of both relapse treatment and relapse prevention. PMID:22976554

  1. 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. PMID:24124042

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

    PubMed Central

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

    2012-01-01

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

  3. 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

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

    PubMed Central

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

    1992-01-01

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

  5. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2016-03-01

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

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

    PubMed

    Fleenor, W A; Stott, G H

    1980-06-01

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

  8. 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.

  9. Systematic Characterization and Comparative Analysis of the Rabbit Immunoglobulin Repertoire

    PubMed Central

    Lavinder, Jason J.; Hoi, Kam Hon; Reddy, Sai T.; Wine, Yariv; Georgiou, George

    2014-01-01

    Rabbits have been used extensively as a model system for the elucidation of the mechanism of immunoglobulin diversification and for the production of antibodies. We employed Next Generation Sequencing to analyze Ig germline V and J gene usage, CDR3 length and amino acid composition, and gene conversion frequencies within the functional (transcribed) IgG repertoire of the New Zealand white rabbit (Oryctolagus cuniculus). Several previously unannotated rabbit heavy chain variable (VH) and light chain variable (VL) germline elements were deduced bioinformatically using multidimensional scaling and k-means clustering methods. We estimated the gene conversion frequency in the rabbit at 23% of IgG sequences with a mean gene conversion tract length of 59±36 bp. Sequencing and gene conversion analysis of the chicken, human, and mouse repertoires revealed that gene conversion occurs much more extensively in the chicken (frequency 70%, tract length 79±57 bp), was observed to a small, yet statistically significant extent in humans, but was virtually absent in mice. PMID:24978027

  10. Low immunoglobulin A levels detected via the tissue transglutaminase assay can reveal previously undetected monoclonal proteins.

    PubMed

    Wallage, M; Dutton, D; Lock, R J

    2016-05-01

    Increased awareness of coeliac disease and the 2009 NICE guidance has led to an increase in patients being screened for Immunoglobulin A deficiency. We have shown previously that this provides an opportunity for the early identification of other underlying primary immunodeficiency, e.g. common variable immunodeficiency. In this context, the underlying gastrointestinal problem appears to be related to bacterial overgrowth. Here, we demonstrate that in addition this also provides an opportunity to reveal underlying secondary immunodeficiency due to other causes in patients with gastrointestinal presentation, notably lymphoproliferative disorders. In one 3-month period, of 60 cases reviewed for low Immunoglobulin A, we found four new paraproteins through this testing route; one symptomatic multiple myeloma, one asymptomatic multiple myeloma, one monoclonal gammopathy of uncertain significance and one in a known chronic lymphocytic leukaemia patient. PMID:26684021

  11. Bringing immunoglobulin knowledge up to date: how should we treat today?

    PubMed Central

    Misbah, S; Kuijpers, T; van der Heijden, J; Grimbacher, B; Guzman, D; Orange, J

    2011-01-01

    Immunoglobulin (Ig) therapy is constantly evolving. Advances in the basic and clinical science of immunoglobulins have provided new perspectives in using polyclonal IgG to treat patients with primary immunodeficiencies. Recent meta-analyses of patient data and outcomes, optimization of IgG administration and better understanding of the IgG receptor variability and clinical effect are new concepts which practising immunologists can use in tailoring their approach to treating patients with primary immunodeficiencies. This manuscript presents the proceedings of a satellite symposium, held in conjunction with the European Society for Immunodeficiencies (ESID) 2010 meeting, to inform attendees about new scientific concepts in IgG therapy, with the goal of empowering expert level evaluation of what optimal IgG therapy is today. PMID:21762127

  12. Bringing immunoglobulin knowledge up to date: how should we treat today?

    PubMed

    Misbah, S; Kuijpers, T; van der Heijden, J; Grimbacher, B; Guzman, D; Orange, J

    2011-10-01

    Immunoglobulin (Ig) therapy is constantly evolving. Advances in the basic and clinical science of immunoglobulins have provided new perspectives in using polyclonal IgG to treat patients with primary immunodeficiencies. Recent meta-analyses of patient data and outcomes, optimization of IgG administration and better understanding of the IgG receptor variability and clinical effect are new concepts which practising immunologists can use in tailoring their approach to treating patients with primary immunodeficiencies. This manuscript presents the proceedings of a satellite symposium, held in conjunction with the European Society for Immunodeficiencies (ESID) 2010 meeting, to inform attendees about new scientific concepts in IgG therapy, with the goal of empowering expert level evaluation of what optimal IgG therapy is today. PMID:21762127

  13. Membranoproliferative glomerulonephritis with masked monotypic immunoglobulin deposits

    PubMed Central

    Larsen, Christopher P; Messias, Nidia C; Walker, Patrick D; Fidler, Mary E; Cornell, Lynn D; Hernandez, Loren H; Alexander, Mariam P; Sethi, Sanjeev; Nasr, Samih H

    2015-01-01

    The diagnosis of membranoproliferative glomerulonephritis (MPGN) has recently undergone change from an electron microscopy-based classification scheme to one based largely on immunofluorescence findings. This change is due to the recognition that many of these cases are driven by abnormalities of the alternative complement cascade, resulting in the concept of C3 glomerulopathy. Here we reviewed our case files to identify those with an MPGN pattern that show false negative staining for monoclonal immunoglobulins by routine immunofluorescence. Monoclonal immunoglobulin deposits were unmasked by performing immunofluorescence on formalin-fixed paraffin embedded tissue after protease digestion. Clinico-pathological details of 16 such cases with a mean serum creatinine of 2.7 mg/dl and mean 24 h proteinuria of 7.1 g were then determined. Hypocomplementemia was present in two-thirds of patients. Fourteen patients had a paraprotein on serum immunofixation, all of which matched the biopsy immunofluorescence staining pattern. Bone marrow biopsy showed plasma cell dyscrasia or B-cell lymphoproliferative disorder in 13 patients. Ten of these patients had findings on biopsy most consistent with C3 glomerulonephritis prior to performing paraffin immunofluorescence. Thus a high index of suspicion is necessary to avoid misdiagnosis in these cases, as many would have been mistakenly diagnosed as C3 glomerulopathy or unclassified MPGN if paraffin immunofluorescence was not performed. PMID:26154922

  14. The immunoglobulins of cold-blooded vertebrates.

    PubMed

    Pettinello, Rita; Dooley, Helen

    2014-01-01

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

  15. Autoantibodies and immunoglobulins among atomic bomb survivors

    SciTech Connect

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

    1994-01-01

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

  16. [Glomerulopathies with organized monoclonal immunoglobulin deposits].

    PubMed

    Touchard, Guy; Bridoux, Frank; Goujon, Jean-Michel

    2016-02-01

    The spectrum of glomerular disorders with organized immunoglobulin (Ig) deposits is heterogeneous. It encompasses 2 mains categories: glomerulopathies with fibrillary deposits are mostly represented by immunoglobulinic amyloidosis (most commonly AL amyloidosis, characterized by monoclonal light chain deposits often of the lambda isotype), and pseudo-amyloid fibrillary glomerulonephritis in which deposits predominantly contain polyclonal IgG4. Glomerulopathies with microtubular deposits include cryoglobulinemic glomerulonephritis (type I and type II, with or without detectable serum cryoglobulin) and glomerulonephritis with organized microtubular monoclonal Ig deposits (GOMMID) also referred to as immunotactoid glomerulopathy. Pathological diagnosis requires meticulous studies by light microscopy (with systematic Congo red staining), immunofluorescence with specific conjugates, and electron microscopy. Ultrastructural studies are required to differentiate amyloid fibrils (8 to 10 nm in external diameter), pseudo-amyloid fibrils (15-20 nm) and microtubules (10 to 50 nm in external diameter, with a central hollow core). Glomerular deposits in type I cryoglobulinemic glomerulonephritis are arranged into parallel straight microtubules similar to those observed in GOMMID, but with different topography that allows distinction between the two entities. Glomerular substructures composed of circulating Igs should be distinguished from collagen fibrils that are commonly observed in glomerular disorders with or without deposition of monoclonal or polyclonal Igs. PMID:26810049

  17. 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

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

    PubMed

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

    1982-01-01

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

  19. Disodium cromoglycate inhibits production of immunoglobulin E.

    PubMed

    Seo, S B; Park, S J; Park, S T; Cho, C C; Park, B H; Lee, S J; Kim, H M; Kajiuchi, T; Shin, T Y

    2001-05-01

    Disodium cromoglycate (DSCG) has been shown to inhibit the release of mediators from mast cells. In the present study, the effect of DSCG on active anaphylactic reaction was studied in mice. DSCG dose-dependently inhibited the active systemic anaphylactic reaction and serum immunoglobulin (Ig)E production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. DSCG strongly inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, DSCG also showed an inhibitory effect on the IgE production. These results suggest that DSCG has an anti-anaphylactic activity by inhibition of IgE production from B cells. PMID:11417850

  20. Intravenous immunoglobulin in pediatrics: A review

    PubMed Central

    Prasad, A.N.; Chaudhary, Sanjay

    2013-01-01

    There has been a rapid expansion of the use of intravenous immunoglobulin (IVIG) for an ever-growing number of conditions. IVIG is used at a ‘replacement dose’ (400–600 mg/kg/month) in antibody deficiencies and is used at a high dose (2 g/kg) as an ‘immunomodulatory’ agent in an increasing number of immune and inflammatory disorders.1 The limitations for IVIG are the cost of the preparation and the need for intravenous infusions. Due to the cost, shortages and growing use of IVIG there have been attempts to develop evidence-based guidelines for the use of IVIG in a wide variety of immune disorders in children and neonates. This commentary provides the recommendations and recent publication regarding the use of IVIG in various conditions in children. PMID:25378784

  1. Immunoglobulin Replacement Therapy in Secondary Hypogammaglobulinemia

    PubMed Central

    Compagno, Nicolò; Malipiero, Giacomo; Cinetto, Francesco; Agostini, Carlo

    2014-01-01

    Immunoglobulin (Ig) replacement therapy dramatically changed the clinical course of primary hypogammaglobulinemias, significantly reducing the incidence of infectious events. Over the last two decades its use has been extended to secondary antibody deficiencies, particularly those related to hematological disorders as lymphoproliferative diseases (LPDs) and multiple myeloma. In these malignancies, hypogammaglobulinemia can be an intrinsic aspect of the disease or follow chemo-immunotherapy regimens, including anti-CD20 treatment. Other than in LPDs the broadening use of immunotherapy (e.g., rituximab) and immune-suppressive therapy (steroids, sulfasalazine, and mycophenolate mofetil) has extended the occurrence of iatrogenic hypogammaglobulinemia. In particular, in both autoimmune diseases and solid organ transplantation Ig replacement therapy has been shown to reduce the rate of infectious events. Here, we review the existing literature about Ig replacement therapy in secondary hypogammaglobulinemia, with special regard for subcutaneous administration route, a safe, effective, and well-tolerated treatment approach, currently well established in primary immunodeficiencies and secondary hypogammaglobulinemias. PMID:25538710

  2. 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

  3. 7th International Immunoglobulin Conference: Immunomodulation.

    PubMed

    Danieli, M G; Shoenfeld, Y

    2014-12-01

    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

  4. 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

  5. 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. PMID:14667846

  6. 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.

  7. Intravenous immunoglobulins in immunodeficiencies: more than mere replacement therapy.

    PubMed

    Kaveri, S V; Maddur, M S; Hegde, P; Lacroix-Desmazes, S; Bayry, J

    2011-06-01

    Intravenous immunoglobulin (IVIG) is a therapeutic compound prepared from pools of plasma obtained from several thousand healthy blood donors. For more than 20 years, IVIG has been used in the treatment of a wide range of primary and secondary immunodeficiencies. IVIG now represents a standard therapeutic option for most antibody deficiencies. Routinely, IVIG is used in patients with X-linked agammaglobulinaemia (XLA), common variable immunodeficiency (CVID), X-linked hyper-IgM, severe combined immunodeficiency, Wiskott-Aldrich syndrome, and selective IgG class deficiency. In addition, IVIG is used extensively in the treatment of a wide variety of autoimmune disorders. IVIG is administered at distinct doses in the two clinical settings: whereas immunodeficient patients are treated with replacement levels of IVIG, patients with autoimmune and inflammatory diseases are administered with very high doses of IVIG. Several lines of experimental evidence gathered in the recent years suggest that the therapeutic beneficial effect of IVIG in immunodeficiencies reflects an active role for IVIG, rather than a mere passive transfer of antibodies. PMID:21466545

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

    PubMed

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

    2015-09-01

    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

  9. 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

  10. Genetically engineered immunoglobulins reveal structural features controlling segmental flexibility.

    PubMed Central

    Schneider, W P; Wensel, T G; Stryer, L; Oi, V T

    1988-01-01

    We have carried out nanosecond fluorescence polarization studies of genetically engineered immunoglobulins to determine the structural features controlling their segmental flexibility. The proteins studied were hybrids of a relatively rigid isotype (mouse IgG1) and a relatively flexible one (mouse IgG2a). They have identical light chains and heavy chain variable regions and have the same combining sites for epsilon-dansyl-L-lysine, a fluorescent hapten. The fluorescence of the bound dansyl chromophore was excited at 348 nm with subnanosecond laser pulses, and the emission in the nanosecond time range was measured with a single-photon-counting apparatus. The emission anisotropy kinetics of the hybrid antibodies revealed that segmental flexibility is controlled by the heavy chain constant region 1 (CH1) as well as by the hinge. In contrast, the CH2 and CH3 domains did not influence segmental flexibility. The hinge and CH1 domains must be properly matched to allow facile movement of the Fab units. Studies of hybrids of IgG1 and IgG2a within CH1 showed that the loop formed by residues 131-139 is important in controlling segmental flexibility. X-ray crystallographic studies by others of human IgG1 have shown that this loop makes several van der Waals contacts with the hinge. Images PMID:3128789

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

    PubMed

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

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development. PMID:27233955

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

    PubMed Central

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

    2015-01-01

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

  13. Immunoglobulin superfamily proteins in Caenorhabditis elegans.

    PubMed

    Teichmann, S A; Chothia, C

    2000-03-10

    The predicted proteins of the genome of Caenorhabditis elegans were analysed by various sequence comparison methods to identify the repertoire of proteins that are members of the immunoglobulin superfamily (IgSF). The IgSF is one of the largest families of protein domain in this genome and likely to be one of the major families in other multicellular eukaryotes too. This is because members of the superfamily are involved in a variety of functions including cell-cell recognition, cell-surface receptors, muscle structure and, in higher organisms, the immune system. Sixty-four proteins with 488 I set IgSF domains were identified largely by using Hidden Markov models. The domain architectures of the protein products of these 64 genes are described. Twenty-one of these had been characterised previously. We show that another 25 are related to proteins of known function. The C. elegans IgSF proteins can be classified into five broad categories: muscle proteins, protein kinases and phosphatases, three categories of proteins involved in the development of the nervous system, leucine-rich repeat containing proteins and proteins without homologues of known function, of which there are 18. The 19 proteins involved in nervous system development that are not kinases or phosphatases are homologues of neuroglian, axonin, NCAM, wrapper, klingon, ICCR and nephrin or belong to the recently identified zig gene family. Out of the set of 64 genes, 22 are on the X chromosome. This study should be seen as an initial description of the IgSF repertoire in C. elegans, because the current gene definitions may contain a number of errors, especially in the case of long sequences, and there may be IgSF genes that have not yet been detected. However, the proteins described here do provide an overview of the bulk of the repertoire of immunoglobulin superfamily members in C. elegans, a framework for refinement and extension of the repertoire as gene and protein definitions improve, and the basis

  14. 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. PMID:21602780

  15. How to use immunoglobulin levels in investigating immune deficiencies.

    PubMed

    Ladomenou, Fani; Gaspar, Bobby

    2016-06-01

    Children are often referred to immunologists for the evaluation of reduced serum immunoglobulins. Knowledge of the immunoglobulin levels in healthy children of different ages is necessary when estimating immunological deficiency states of various kinds. After the measurement of the serum levels of the three major isotypes, examination of the capacity of the child to form antibodies to several antigens is a reasonable next step in the evaluation. We can rely on vaccine responses to make the distinction between significant primary immunodeficiency diseases and transiently low immunoglobulin levels. On the other hand, normal values of IgM, IgG and IgA are not always enough to exclude a more serious condition. Regardless of immunoglobulin concentrations, if a child's history indicates that further evaluation is warranted, a complete humoral immunity study should be carried out, including IgG subclasses, specific antibody responses and identification of B lymphocyte populations. PMID:26987724

  16. Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier.

    PubMed

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen; Khorooshi, Reza; Owens, Trevor

    2015-08-01

    To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin-4 in cerebrospinal fluid, aquaporin-4-immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown. PMID:26339679

  17. Immunoglobulin G4-related large thoraco-abdominal aortic aneurysm.

    PubMed

    Sekine, Yuji; Yamamoto, Shin; Fujikawa, Takuya; Sasaguri, Shiro

    2016-07-01

    We report a case of immunoglobulin G4-related large thoraco-abdominal aortic aneurysm in a 38-year old man. Preoperative contrast-enhanced computed tomography revealed that the mid-descending thoracic aorta was extremely enlarged and the maximum diameter of the aneurysm was 92 mm. The patient underwent thoraco-abdominal aortic replacement through a thoraco-abdominal incision under left heart bypass. The postoperative pathological examination diagnosed immunoglobulin G4-related aortic aneurysm. PMID:27059069

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

    PubMed Central

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

    2015-01-01

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

  19. Immobilization of immunoglobulins on silica surfaces. Stability.

    PubMed Central

    Jönsson, U; Malmqvist, M; Rönnberg, I

    1985-01-01

    The development of new immunosensors based on surface-concentration-measuring devices requires a stable and reproducible immobilization of antibodies on well-characterized solid surfaces. We here report on the immobilization of immunoglobulin G (IgG) on chemically modified silica surfaces. Such surfaces may be used in various surface-oriented analytical methods. Reactive groups were introduced to the silica surfaces by chemical-vapour deposition of silane. The surfaces were characterized by ellipsometry, contact-angle measurements and scanning electron microscopy. IgG covalently bound by the use of thiol-disulphide exchange reactions, thereby controlling the maximum number of covalent bonds to the surface, was compared with IgG adsorbed on various silica surfaces. This comparison showed that the covalently bound IgG has a superior stability when the pH was lowered or incubation with detergents, urea or ethylene glycol was carried out. The result was evaluated by ellipsometry, an optical technique that renders possible the quantification of amounts of immobilized IgG. The results outline the possibilities of obtaining a controlled covalent binding of biomolecules to solid surfaces with an optimal stability and biological activity of the immobilized molecules. Images Fig. 3. PMID:2988497

  20. Adverse effects of human immunoglobulin therapy.

    PubMed

    Stiehm, E Richard

    2013-07-01

    Human immunoglobulin (IG) is used for IgG replacement therapy in primary and secondary immunodeficiency, for prevention and treatment of certain infections, and as an immunomodulatory agent for autoimmune and inflammatory disorders. IG has a wide spectrum of antibodies to microbial and human antigens. Several high-titered IGs are also available enriched in antibodies to specific viruses or bacterial toxins. IG can be given intravenously (IGIV), intramuscularly (IGIM) or by subcutaneous infusions (SCIG). Local adverse reactions such as persistent pain, bruising, swelling and erythema are rare with IGIV infusions but common (75%) with SCIG infusions. By contrast, adverse systemic reactions are rare with SCIG infusions but common with IGIV infusions, occurring as often as 20% to 50% of patients and 5% to 15% of all IGIV infusions. Systemic adverse reactions can be immediate (60% of reactions) occurring within 6 hours of an infusion, delayed (40% of reactions) occurring 6 hours-1 week after an infusion, and late (less than 1% of reactions), occurring weeks and months after an infusion. Immediate systemic reactions such as head and body aches, chills and fever are usually mild and readily treatable. Immediate anaphylactic and anaphylactoid reactions are uncommon. The most common delayed systemic reaction is persistent headache. Less common but more serious delayed reactions include aseptic meningitis, renal failure, thromboembolism, and hemolytic reactions. Late reactions are uncommon but often severe, and include lung disease, enteritis, dermatologic disorders and infectious diseases. The types, incidence, causes, prevention, and management of these reactions are discussed. PMID:23835249

  1. Efficacy of Intravenous Immunoglobulin in Neurological Diseases.

    PubMed

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

    2016-01-01

    Owing to its anti-inflammatory efficacy in various autoimmune disease conditions, intravenous immunoglobulin (IVIG)-pooled IgG obtained from the plasma of several thousands individuals-has been used for nearly three decades and is proving to be efficient in a growing number of neurological diseases. IVIG therapy has been firmly established for the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, either as first-line therapy or adjunctive treatment. IVIG is also recommended as rescue therapy in patients with worsening myasthenia gravis and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. Subcutaneous rather than intravenous administration of IgG is gaining momentum because of its effectiveness in patients with primary immunodeficiency and the ease with which it can be administered independently from hospital-based infusions. The demand for IVIG therapy is growing, resulting in rising costs and supply shortages. Strategies to replace IVIG with recombinant products have been developed based on proposed mechanisms that confer the anti-inflammatory activity of IVIG, but their efficacy has not been tested in clinical trials. This review covers new developments in the immunobiology and clinical applications of IVIG in neurological diseases. PMID:26400261

  2. Maternal immunoglobulin E and childhood leukemia.

    PubMed

    Chang, Jeffrey S; Buffler, Patricia A; Metayer, Catherine; Chokkalingam, Anand P; Patoka, Joe; Kronish, Daniel; Wiemels, Joseph L

    2009-08-01

    Childhood leukemia, particularly acute lymphoblastic leukemia (ALL), has long been hypothesized to be affected by abnormal immune responses to microbial challenges stemming from a lack of immune modulation in early childhood. Studies of allergies suggest that a child's immune development may be modulated by maternal immune status. We conducted a study to explore the relationship between maternal immunoglobulin E (IgE) and childhood leukemia and to investigate whether maternal immune status can influence childhood leukemia risk. Serum total and specific IgE (respiratory and food) were measured in biological mothers of 352 children (193 healthy controls and 159 leukemia cases, including 139 ALL cases) ages <8 years who were enrolled in the Northern California Childhood Leukemia Study. Odds ratios associated with maternal IgE were calculated using unconditional logistic regression adjusted for child's age, sex, race/ethnicity, and annual household income. A positive association between childhood leukemia or ALL and elevated levels of maternal serum total IgE was observed, especially among Hispanics. In addition, a positive association was observed between childhood leukemia or ALL and maternal respiratory or food IgE status. These results suggest that maternal immune function may play a crucial role in the etiology of childhood leukemia, although additional studies need to be conducted to confirm the results of this study and provide a perspective on mechanisms. PMID:19622720

  3. Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis.

    PubMed

    Grove, P; Neale, P H; Peck, M; Schiller, B; Haas, M

    1998-01-01

    We report here a case of fibrillary glomerulonephritis arising in a 43-year-old man with a polyclonal gammopathy, who presented with progressive renal insufficiency, microscopic hematuria, and mild proteinuria (0.7 g/d). Ultrastructural studies showed deposits of randomly oriented fibrils in the glomerular mesangium and adjacent portions of some glomerular basement membranes, with a mean fibril thickness of 14.3 nm, highly consistent with fibrillary glomerulonephritis. The Congo red stain was negative on histologic sections. Immunofluorescence studies revealed strong mesangial and focal glomerular capillary staining for immunoglobulin (Ig) G, complement (C) 3, and kappa light chains, with minimal staining for IgA, IgM, C1q, or lambda light chains. The IgG present was entirely of the IgG1 subclass. This case is quite unusual for fibrillary glomerulonephritis, which typically presents with polyclonal IgG deposits and IgG4 as the dominant IgG subclass present. Monoclonal deposits are more frequently associated with immunotactoid glomerulopathy, characterized ultrastructurally by microtubule-like structures 30 to 50 nmn thick, often in parallel arrays. The present case illustrates that although fibrillary glomerulonephritis and immunotactoid glomerulopathy might be distinguishable on ultrastructural grounds, there is overlap between these two entities with respect to the potential composition of the glomerular deposits present. PMID:9556416

  4. 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

  5. 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. PMID:26900989

  6. Clinical applications of intravenous immunoglobulins in neurology.

    PubMed

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

    2009-12-01

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

  7. [Treatments with immunoglobulin and thrombotic adverse events].

    PubMed

    Darnige, L; Lillo-Le Louët, A

    2014-01-01

    Treatments with intravenous or subcutaneous immunoglobulin (Ig) are used in a broad variety of disorders. Tolerance of Ig is usually good but adverse events, including some serious ones, have been reported and may differ among different Ig preparations. Thrombotic complications occur in 0.6 to 13% of cases and can involve arterial or venous circulation, rarely both. Deep venous thrombosis with or without pulmonary embolism, stroke or myocardial infarction remained the most frequent thrombotic complications. Some risk factors have been identified, mainly old age, multiple cardiovascular risk factors, and past history of thrombo-embolic manifestations. Several mechanisms are suggested to explain this increased risk of thrombotic complications. Indeed, Ig treatments increase the plasma viscosity, increase and activate platelets, can trigger the coagulation cascade through the presence of activated factor XI in some Ig preparations, and release vasoactive molecules responsible for vasospasm. Patients have to be carefully monitored and risk factors to be identified as soon as possible. The role of antiplatelets or anticoagulation is not well determined but should probably be proposed to patients with high risk. PMID:24011913

  8. 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.

  9. Salivary Microbiota Associated with Immunoglobulin A Nephropathy.

    PubMed

    Piccolo, Maria; De Angelis, Maria; Lauriero, Gabriella; Montemurno, Eustacchio; Di Cagno, Raffaella; Gesualdo, Loreto; Gobbetti, Marco

    2015-08-01

    This study aimed at investigating the salivary microbiota of 28 patients affected by immunoglobulin A nephropathy (IgAN). Fourteen healthy volunteers (HC) were used as control. Compared to HC, the number of some cultivable bacteria groups (e.g., total anaerobes) significantly (P < 0.05) decreased in the salivary samples of IgAN patients. Total bacteria from salivary samples of IgAN patients and HC subjects were analyzed by pyrosequencing of 16S rRNA gene. Paired t test showed no significant (P > 0.05) differences of alpha-diversity parameters (OTU, ACE, Chao1, and Shannon index) between the salivary samples of HC and IgAN patients. The difference for the community structure was further analyzed using three phylogeny-based beta-diversity measures. Compared to HC, the ratio between Firmicutes/Proteobacteria markedly decreased in IgAN patients. Gemella haemolysins, Granulicatella adiacens, and Veillonella parvula were positively associated (P < 0.05) with HC. Within the phylum Bacteroidetes, Prevotella species (Prevotella nigrescens, Prevotella intermedia, Prevotella pallens, and Prevotella salivae) were the highest in HC. The only exception was for Prevotella aurantiaca. Compared to HC, the percentage of abundance of some species, belonging to Pasteurellaceae family (e.g., Haemophylus parainfluenzae), increased in IgAN patients. Fusobacteriaceae (Fusobacterium) and Corynebacterium sp. also differed between the salivary samples of HC and IgAN patients. PMID:25763757

  10. 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.

  11. The formation of immunoglobulins by human tissues in vitro

    PubMed Central

    Van Furth, R.; Schuit, Henrica R. E.; Hijmans, W.

    1966-01-01

    The formation of immunoglobulins by human tissues was studied by three techniques: (1) Autoradiography of the immunoelectrophoretic pattern of culture fluids of tissue fragments or cell suspensions in a medium with radio-active amino acids; (2) immunofluorescent staining of the tissue sections or cell suspensions, before incubation, with antisera specific for one immunoglobulin; and (3) histological and cytological study of the samples. The paper gives a detailed description of the techniques applied and evaluates the specificity of the immunological methods used. Various control experiments were performed: Incubation of dead tissues or normal serum in the radioactive culture medium excluded the adsorption of [14C]amino acids on to immunoglobulins. Cultures of tissue fragments in the presence of puromycin showed an inhibition of the synthesis of [14C]immunoglobulins. Autoradiography of a `fingerprint' of radioactive IgG demonstrated radioactive amino acids present in different peptides of the synthesized molecule. From these control experiments it can be concluded that the labelling of the immunoglobulins is based on the incorporation of [14C]amino acids during incubation in vitro. The specificity of the immunofluorescent staining was evaluated by immunodiffusion of the antisera and conjugates, by blocking procedures and by specific staining of bone-marrow samples from patients with various immunoglobulin abnormalities. ImagesFIG. 3FIG. 4FIG. 5 PMID:4161984

  12. Immunoglobulin Expression in Non-Lymphoid Lineage and Neoplastic Cells

    PubMed Central

    Chen, Zhengshan; Qiu, Xiaoyan; Gu, Jiang

    2009-01-01

    It has traditionally been believed that the production of immunoglobulin (Ig) molecules is restricted to B lineage cells. However, immunoglobulin genes and proteins have been recently found in a variety of types of cancer cells, as well as some proliferating epithelial cells and neurons. The immunoglobulin molecules expressed by these cells consist predominantly of IgG, IgM, and IgA, and the light chains expressed are mainly kappa chains. Recombination activating genes 1 and 2, which are required for V(D)J recombination, are also expressed in these cells. Knowledge about the function of these non-lymphoid cell-derived immunoglobulins is limited. Preliminary data suggests that Ig secreted by epithelial cancer cells has some unidentified capacity to promote the growth and survival of tumor cells. As immunoglobulins are known to have a wide spectrum of important functions, the discovery of non-lymphoid cells and cancers that produce immunoglobulin calls for in-depth investigation of the functional and pathological significance of this previously unrecognized phenomenon. PMID:19246641

  13. Use of subcutaneous immunoglobulin in primary immune deficiencies

    PubMed Central

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

    2016-01-01

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

  14. Diagnosis of toxoplasmosis by joint detection of immunoglobulin A and immunoglobulin M.

    PubMed Central

    Arcavi, M; Orfus, G; Griemberg, G

    1997-01-01

    An indirect immunofluorescence test with total anti-human immunoglobulin conjugate (IgG,A,M-IIF) can be used for joint detection of immunoglobulin A (IgA) and IgM antibodies, provided serum IgG is previously absorbed with anti-human IgG. To determine the validity of the IgG,A,M-IIF assay with absorbed sera, the results obtained were compared with those obtained by methods routinely used for the detection of acute-phase markers, IgA and IgM IIF and enzyme immunoassay. Accordingly, 114 serum samples were selected from patients showing titers of > or = 1:1,024 by IgG,A,M-IIF. (i) In 90 of the samples, neither IgA nor IgM was detected by any of the methods employed; (ii) the remaining 24 samples showed IgA and/or IgM. In all cases, the IgG,A,M-IIF assay with absorbed sera was positive. These comparative data support the use of IgG,A,M-IIF, performed with absorbed and unabsorbed sera simultaneously, for determining the presence of specific IgG, IgA, and IgM by employing a single technique (IIF), one conjugate (anti-IgG,A,M), and only one sample (with and without previous absorption), thus providing a useful initial tool for the diagnosis of toxoplasmosis. PMID:9163460

  15. 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.

  16. Immunoglobulin A responses to Puumala hantavirus.

    PubMed

    de Carvalho Nicacio, C; Björling, E; Lundkvist, A

    2000-06-01

    Puumala hantavirus (PUUV) causes nephropathia epidemica (NE), a form of haemorrhagic fever with renal syndrome that occurs in northern and central Europe. The immunoglobulin A (IgA) response in NE patients was studied. The levels of total serum IgA in acute-phase samples from NE patients were found to be significantly elevated when compared with the levels in healthy controls. ELISAs for detection of the IgA1 and IgA2 responses against each PUUV structural protein (N, G1 and G2) were developed and evaluated. Sequential sera from NE patients (acute, convalescent, 2-year) and 10-20 year NE-convalescent sera were examined. Most patients developed detectable levels of IgA1 against N and G2, while the G1 responses were low or undetectable. Seven of nine 10-20 year sera contained virus-specific IgA1, which may indicate the prolonged presence of viral antigens after the initial infection. PEPSCAN analysis revealed several IgA-reactive antigenic regions in the N protein. Serum IgA and IgG was purified by affinity chromatography and examined by a virus-neutralization assay. Three of five sera from acute-phase NE patients contained neutralizing IgA1. The diagnostic potential of the PUUV-specific IgA1 response was evaluated. The N and G2 assays showed specificities of 100% with sensitivities of 91 and 84%, respectively, compared with an IgM mu-capture ELISA. Several NE patients, clinically diagnosed for acute PUUV infection, with borderline or undetectable levels of PUUV-specific IgM, were found to be highly positive for the presence of PUUV N-specific serum IgA1, proving the diagnostic value of IgA analysis as a complement to detection of IgM. PMID:10811929

  17. 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

  18. 7th International Immunoglobulin Conference: Immunomodulation.

    PubMed

    Danieli, M G; Shoenfeld, Y

    2014-12-01

    Immunomodulation uses synthetic, natural and recombinant preparations to modify the immune response to a desired level, typically to treat specific autoimmune diseases, as will be discussed in this section. Rheumatoid arthritis (RA) is a common systemic autoimmune disease, affecting 1% of the population worldwide. Currently, a first-line disease-modifying therapy for RA is methotrexate; however, more than 40 monoclonal antibodies are in use or under investigation for the treatment of RA. This panoply of biological disease-modifying agents means that clinicians can make use of drugs with different mechanisms of action should one type become ineffective. In autoimmune pemphigus conditions, identification of pathogenic autoantibodies against intercellular cadherin desmoglein 1 and/or 3 antigens is one of the criteria for appropriate diagnosis. In pemphigoid conditions, autoantibodies are directed against bullous pemphigoid antigens BP230 and BP180, and in both types of immunobullous disease intravenous immunoglobulin (IVIg), as adjuvant therapy in combination with a cytotoxic drug, is effective in reducing autoantibody levels, disease severity and background steroid use. Further studies are required to establish the role of monoclonal antibodies in the treatment of autoimmune bullous disease. IVIg may also be effective in another at-risk population with autoimmune disease, namely secondary recurrent miscarriage (RM). However, the mechanism of action of IVIg in secondary RM is largely unknown, although levels of natural killer cell biomarkers, particularly CD56(+) , have been shown to decline after IVIg treatment. Data from meta-analyses of heterogeneous placebo-controlled trials indicate that IVIg may be effective in secondary RM, but most trials to date have used immunomodulatory doses lower than those considered to be efficient in autoimmune disease. The results of a recently completed study may help to address this question. PMID:25546784

  19. AID-initiated purposeful mutations in immunoglobulin genes.

    PubMed

    Goodman, Myron F; Scharff, Matthew D; Romesberg, Floyd E

    2007-01-01

    Exposure brings risk to all living organisms. Using a remarkably effective strategy, higher vertebrates mitigate risk by mounting a complex and sophisticated immune response to counter the potentially toxic invasion by a virtually limitless army of chemical and biological antagonists. Mutations are almost always deleterious, but in the case of antibody diversification there are mutations occurring at hugely elevated rates within the variable (V) and switch regions (SR) of the immunoglobulin (Ig) genes that are responsible for binding to and neutralizing foreign antigens throughout the body. These mutations are truly purposeful. This chapter is centered on activation-induced cytidine deaminase (AID). AID is required for initiating somatic hypermutation (SHM) in the V regions and class switch recombination (CSR) in the SR portions of Ig genes. By converting C --> U, while transcription takes place, AID instigates a cascade of mutational events involving error-prone DNA polymerases, base excision and mismatch repair enzymes, and recombination pathways. Together, these processes culminate in highly mutated antibody genes and the B cells expressing antibodies that have achieved optimal antigenic binding undergo positive selection in germinal centers. We will discuss the biological role of AID in this complex process, primarily in terms of its biochemical properties in relation to SHM in vivo. The chapter also discusses recent advances in experimental methods to characterize antibody dynamics as a function of SHM to help elucidate the role that the AID-induced mutations play in tailoring molecular recognition. The emerging experimental techniques help to address long-standing conundrums concerning evolution-imposed constraints on antibody structure and function. PMID:17560274

  20. 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

  1. Evolutionary genomics of immunoglobulin-encoding Loci in vertebrates.

    PubMed

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

    2012-04-01

    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

  2. The Immunobiology of Immunoglobulin G4.

    PubMed

    Lighaam, Laura C; Rispens, Theo

    2016-08-01

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

  3. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Kothapalli, Naga Rama; Fugmann, Sebastian D

    2011-04-01

    Activation-induced cytidine deaminase (AID) is a key enzyme for antibody-mediated immune responses. Antibodies are encoded by the immunoglobulin genes and AID acts as a transcription-dependent DNA mutator on these genes to improve antibody affinity and effector functions. An emerging theme in field is that many transcribed genes are potential targets of AID, presenting an obvious danger to genomic integrity. Thus there are mechanisms in place to ensure that mutagenic outcomes of AID activity are specifically restricted to the immunoglobulin loci. Cis-regulatory targeting elements mediate this effect and their mode of action is probably a combination of immunoglobulin gene specific activation of AID and a perversion of faithful DNA repair towards error-prone outcomes. PMID:21295456

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

    PubMed Central

    Kothapalli, Naga Rama; Fugmann, Sebastian D.

    2011-01-01

    Activation-induced cytidine deaminase (AID) is a key enzyme for antibody-mediated immune responses. Antibodies are encoded by the immunoglobulin genes and AID acts as a transcription-dependent DNA mutator on these genes to improve antibody affinity and effector functions. An emerging theme in field is that many transcribed genes are potential targets of AID, presenting an obvious danger to genomic integrity. Thus there are mechanisms in place to ensure that mutagenic outcomes of AID activity are specifically restricted to the immunoglobulin loci. Cis-regulatory targeting elements mediate this effect and their mode of action is likely a combination of immunoglobulin gene specific activation of AID and a perversion of faithful DNA repair towards error-prone outcomes. PMID:21295456

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  9. New monoclonal antibodies to the Ebola virus glycoprotein: Identification and analysis of the amino acid sequence of the variable domains.

    PubMed

    Panina, A A; Aliev, T K; Shemchukova, O B; Dement'yeva, I G; Varlamov, N E; Pozdnyakova, L P; Bokov, M N; Dolgikh, D A; Sveshnikov, P G; Kirpichnikov, M P

    2016-03-01

    We determined the nucleotide and amino acid sequences of variable domains of three new monoclonal antibodies to the glycoprotein of Ebola virus capsid. The framework and hypervariable regions of immunoglobulin heavy and light chains were identified. The primary structures were confirmed using massspectrometry analysis. Immunoglobulin database search showed the uniqueness of the sequences obtained. PMID:27193713

  10. 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. PMID:19220771

  11. 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. PMID:25610537

  12. Russell body duodenitis with immunoglobulin kappa light chain restriction

    PubMed Central

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

    2015-01-01

    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. PMID:25610537

  13. 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

  14. 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. PMID:25185680

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

    PubMed Central

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

    2014-01-01

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

  16. Radioimmunoassay of free light chains of immunoglobulins in urine

    SciTech Connect

    Robinson, E.L.; Gowland, E.; Ward, I.D.; Scarffe, J.H.

    1982-01-01

    Radioimmunoassays for kappa and lambda light chains of immunoglobulins in urine are described. The assays, which involve antisera to free light chains, were sufficiently sensitive to measure the light chains in unconcentrated urine from healthy subjects. The usefulness of the assays in clinical practice is illustrated by measurements of light chain excretion by patients, including serial studies on patients undergoing treatment for myeloma.

  17. [Hypocomplementemic urticarial vasculitis syndrome. Successful therapy with intravenous immunoglobulins].

    PubMed

    Staubach-Renz, P; von Stebut, E; Bräuninger, W; Maurer, M; Steinbrink, K

    2007-08-01

    Autoimmune diseases can initially present as chronic urticaria. We describe the course of a patient with hypocomplementemic urticarial vasculitis syndrome (HUVS) as well as his successful treatment with high-dose intravenous immunoglobulins (IVIG). HUVS was diagnosed clinically and confirmed by histology and laboratory studies. After only one cycle with IVIG (2 g/kg) all HUVS symptoms were significantly decreased. PMID:17453168

  18. 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. PMID:19505725

  19. 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

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

    PubMed

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

    2016-01-01

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

  1. 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

  2. Biological Activities of Rabbit Immunoglobulin M and Immunoglobulin G Antibodies to Pseudomonas aeruginosa

    PubMed Central

    Bjornson, Ann B.; Michael, J. Gabriel

    1970-01-01

    Immunoglobulin (Ig)M and IgG antibodies, prepared in the rabbit against the protective antigen of Pseudomonas aeruginosa P4, were compared as to their biological activities in vitro and in vivo. In vitro biological activities of these antibodies were determined by passive hemagglutination, bactericidal, and opsonophagocytic tests. Increased effectiveness of IgM over IgG on a molar basis was demonstrated in all of these tests. However, in mouse protection tests, in which the purified globulins were injected intraperitoneally 4 hr prior to challenge with P. aeruginosa suspended in hog gastric mucin, IgM anticapsular antibody was found to be less effective than IgG antibody. The exact mechanism whereby IgG antibody exerts more protective ability than IgM antibody is still unknown. We present evidence to suggest that the difference in activity between the two classes of antibody is due to the ability of the IgG antibody to enter the bloodstream more rapidly than the IgM antibody and also to the ability of IgG to diffuse rapidly through the tissues of the organs. PMID:16557861

  3. neu protooncogene fused to an immunoglobulin heavy chain gene requires immunoglobulin light chain for cell surface expression and oncogenic transformation.

    PubMed Central

    Flanagan, J G; Leder, P

    1988-01-01

    The protein encoded by the neu protooncogene (human gene symbol NGL for neuro/glioblastoma-derived) is a member of the surface receptor/tyrosine kinase family. Though its structure suggests that it can transduce a transmembrane signal, neither its extracellular ligand nor its critical intracellular substrates are known. To explore the functional properties of the protein encoded by neu, we created a fusion gene that joins the cytoplasmic domain of neu to the extracellular portion of an immunoglobulin heavy chain. The localization of the fusion polypeptide can then be controlled by coexpression with immunoglobulin light chain. In the absence of light chain, the heavy chain-neu polypeptide is expressed intracellularly and has no transforming activity. By contrast, in the presence of light chain the fusion polypeptide is expressed at the cell surface and produces tumorigenic foci. Thus, transformation apparently requires expression at the cell surface, where the neu intracellular domain can interact with components that are localized to the plasma membrane. The fusion protein is active in cellular transformation when the transmembrane domain is derived either from neu or from immunoglobulin, indicating that the neu transmembrane domain is not specifically required for transformation, although neu activation in tumors is known to result from a point mutation in this region. The extracellular immunoglobulin heavy and light chain domains of the fusion protein form a functional binding site that allows antigen to modulate its activity, reversing the transforming effect. Images PMID:2903500

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

    PubMed

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

    2013-01-01

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

  5. Immunoparesis in MGUS - Relationship of uninvolved immunoglobulin pair suppression and polyclonal immunoglobuline levels to MGUS risk categories.

    PubMed

    Pika, T; Lochman, P; Sandecka, V; Maisnar, V; Minarik, J; Tichy, M; Zapletalova, J; Solcova, L; Scudla, V; Hajek, R

    2015-01-01

    Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic, potentially malignant condition. It has been established that annually approximately 1-2% of MGUS cases transforms into one of the malignant forms of monoclonal gammopathies. Progression risk factors include the quantity and type of M-protein, and namely the ratio of free light immunoglobulin chains (FLC). These factors, enable purposeful stratification of MGUS individuals. Some authors consider suppression of polyclonal immunoglobulin levels to be another progression factor. The aim of the study was to compare polyclonal immunoglobulin (PIg) levels with uninvolved heavy/light chain pair (HLC) levels in order to verify the degree of immunoparesis depending on MGUS risk category (0-3). The analyzed set consisted of 159 serum samples from MGUS patients (102 IgG, 57 IgA), who were stratified into 4 risk groups (0 - low, 1 - low-intermediate, 2 - high-intermediate and 3 - high risk of transformation). The results of analysis showed that with increasing degree of MGUS increases risk of immune paresis defined by decreasing levels of polyclonal immunoglobulins, ie. IgA and IgM in the case of IgG MGUS, respectively, IgG and IgM in case of IgA MGUS. Significant differences were also found when analyzing the levels of uninvolved HLC pairs IgG kappa (resp. IgG lambda) in IgG lambda (IgG kappa) dominant secretion. In the case of MGUS with IgA isotype, the results were similar. Discovery of the connection between the degree of immunosuppression and the level of MGUS risk contributes to our understanding of the relationship between biology, development and potential malignant transformation of MGUS. It is apparent that uninvolved HLC pair assay enables more reliable identification of at-risk MGUS patients than a simple quantitative assay for polyclonal immunoglobulins alone. PMID:26278155

  6. 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. PMID:23058015

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

    PubMed Central

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

    2015-01-01

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

  8. Partial versus Productive Immunoglobulin Heavy Locus Rearrangements in Chronic Lymphocytic Leukemia: Implications for B-Cell Receptor Stereotypy

    PubMed Central

    Tsakou, Eugenia; Agathagelidis, Andreas; Boudjoghra, Myriam; Raff, Thorsten; Dagklis, Antonis; Chatzouli, Maria; Smilevska, Tatjana; Bourikas, George; Merle-Beral, Helene; Manioudaki-Kavallieratou, Eleni; Anagnostopoulos, Achilles; Brüggemann, Monika; Davi, Frederic; Stamatopoulos, Kostas; Belessi, Chrysoula

    2012-01-01

    The frequent occurrence of stereotyped heavy complementarity-determining region 3 (VH CDR3) sequences among unrelated cases with chronic lymphocytic leukemia (CLL) is widely taken as evidence for antigen selection. Stereotyped VH CDR3 sequences are often defined by the selective association of certain immunoglobulin heavy diversity (IGHD) genes in specific reading frames with certain immunoglobulin heavy joining (IGHJ ) genes. To gain insight into the mechanisms underlying VH CDR3 restrictions and also determine the developmental stage when restrictions in VH CDR3 are imposed, we analyzed partial IGHD-IGHJ rearrangements (D-J) in 829 CLL cases and compared the productively rearranged D-J joints (that is, in-frame junctions without junctional stop codons) to (a) the productive immunoglobulin heavy variable (IGHV )-IGHD-IGHJ rearrangements (V-D-J) from the same cases and (b) 174 D-J rearrangements from 160 precursor B-cell acute lymphoblastic leukemia cases (pre-B acute lymphoblastic leukemia [ALL]). Partial D-J rearrangements were detected in 272/829 CLL cases (32.8%). Sequence analysis was feasible in 238 of 272 D-J rearrangements; 198 of 238 (83.2%) were productively rearranged. The D-J joints in CLL did not differ significantly from those in pre-B ALL, except for higher frequency of the IGHD7-27 and IGHJ6 genes in the latter. Among CLL carrying productively rearranged D-J, comparison of the IGHD gene repertoire in productive V-D-J versus D-J revealed the following: (a) overuse of IGHD reading frames encoding hydrophilic peptides among V-D-J and (b) selection of the IGHD3-3 and IGHD6-19 genes in V-D-J junctions. These results document that the IGHD and IGHJ gene biases in the CLL expressed VH CDR3 repertoire are not stochastic but are directed by selection operating at the immunoglobulin protein level. PMID:21968789

  9. Common Variable Immunodeficiency.

    PubMed

    Saikia, Biman; Gupta, Sudhir

    2016-04-01

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

  10. Two young stroke patients associated with regular intravenous immunoglobulin (IVIg) therapy.

    PubMed

    Nakano, Yumiko; Hayashi, Takeshi; Deguchi, Kentaro; Sato, Kota; Hishikawa, Nozomi; Yamashita, Toru; Ohta, Yasuyuki; Takao, Yoshiki; Morio, Tomohiro; Abe, Koji

    2016-02-15

    We recently experienced 2 young adult patients who developed ischemic stroke after regular intravenous immunoglobulin (IVIg) therapy for agammaglobulinemia with diagnosis of common variable immunodeficiency (CVID) in their childhood. Patient 1 was 26-year-old woman, who developed Wallenberg's syndrome 6 days after the last IVIg therapy, but had no further stroke recurrence with cilostazol later. Patient 2 was 37-year-old man, who developed recurrent cerebral infarction in the territory of bilateral lenticulostriate branches like branch atheromatous disease (BAD) several days after the IVIg therapy. However, he had no further stroke recurrence after bone marrow transplantation (BMT) therapy for his lymphoproliferative disorder. It was suggested that IVIg therapy was associated to these different types of ischemic stroke in our 2 young adult patients with minimal vascular risk factors. Although IVIg therapy is widely used as a relatively safe medication for immunodeficiency disorders or autoimmune diseases, we need to pay more attention to stroke occurrence with regular IVIg therapy. PMID:26810508

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

    NASA Astrophysics Data System (ADS)

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

    1994-08-01

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

  12. Management and production factors influencing immunoglobulin G1 concentration in colostrum from Holstein cows.

    PubMed

    Pritchett, L C; Gay, C C; Besser, T E; Hancock, D D

    1991-07-01

    Immunoglobulin G1 concentration was measured in 919 first milking colostrums from Holstein cows during a 4-yr period on a commercial dairy farm. Sources of variation analyzed for effect on colostral IgG1 concentration were season of calving, lactation number, dry period length, intercalving interval, complete lactation milk and fat production, weight of first milking colostrum, and time from calving to first milking. Weight of first milking colostrum was the variable most highly correlated (negatively) with colostral IgG1 concentration (r = -.29). Weight of first milking colostrum and lactation number of the cow were the most significant discriminators between colostrum of low and high IgG1 concentration. The implications of these results for colostrum feeding management are discussed. PMID:1894821

  13. Immunoglobulin gene analysis in polyneuropathy associated with IgM monoclonal gammopathy.

    PubMed

    Eurelings, Marijke; Notermans, Nicolette C; Lokhorst, Henk M; van Kessel, Berris; Jacobs, Bart C; Wokke, John H J; Sahota, Surinder S; Bloem, Andries C

    2006-06-01

    Antineural antibody activity is the implicated pathogenic mechanism in polyneuropathy associated with monoclonal gammopathy. Recognition of antigen depends on immunoglobulin variable regions, encoded by V genes. We studied V(H)DJ(H) and V(L)J(L) gene use in monoclonal B cells by clonal analysis in 20 patients with polyneuropathy and IgM monoclonal gammopathy. V genes associated with bacterial responses appear over-represented and V(H)3-23 was preferentially used, without association with specific D, J(H) or V(L)J(L). V genes revealed somatic mutation and intraclonal variation was found in 9 of 20 patients. Polyneuropathy associated with monoclonal gammopathy may be caused by an immune response to bacterial antigens, which recruit somatically mutated autoreactive B cells. PMID:16600385

  14. Isolation of myeloma variants with predefined variant surface immunoglobulin by cell sorting.

    PubMed Central

    Liesegang, B; Radbruch, A; Rajewsky, K

    1978-01-01

    We describe a procedure for the isolation of somatic cell variants in which gene products are expressed on the cell surface that are not expressed in the wild type. Cloned cells of the myeloma line MPC 11, which expresses an IgG2b protein, were incubated with an antiserum specific for IgGI and IgG2a. Cells reacting with this antiserum were stained with a fluorescent anti-antiserum and enriched in three cycles of sorting in the fluorescence-activated cell sorter and subsequent growth in vitro. From the enriched population two variants were isolated by cloning in soft agar. One of them expressed a variant immunoglobulin that types serologically as an IgG2a but whose variable portion was idiotypically related to that of the MPC 11 wild-type protein. Images PMID:308657

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

    PubMed Central

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

    2016-01-01

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

  16. Glycosaminoglycans promote fibril formation by amyloidogenic immunoglobulin light chains through a transient interaction

    PubMed Central

    Martin, Douglas J.; Ramirez-Alvarado, Marina

    2011-01-01

    Amyloid formation occurs when a precursor protein misfolds and aggregates, forming a fibril nucleus that serves as a template for fibril growth. Glycosaminoglycans are highly charged polymers known to associate with tissue amyloid deposits that have been shown to accelerate amyloidogenesis in vitro. We studied two immunoglobulin light chain variable domains from light chain amyloidosis patients with 90% sequence identity, analyzing their fibril formation kinetics and binding properties with different glycosaminoglycan molecules. We find that the less amyloidogenic of the proteins shows a weak dependence on glycosaminoglycan size and charge, while the more amyloidogenic protein responds only minimally to changes in the glycosaminoglycan. These glycosaminoglycan effects on fibril formation do not depend on a stable interaction between the two species but still show characteristic traits of an interaction-dependent mechanism. We propose that transient, predominantly electrostatic interactions between glycosaminoglycans and the precursor proteins mediate the acceleration of fibril formation in vitro. PMID:21640469

  17. 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. PMID:26971743

  18. Immunoglobulin G3 and immunoglobulin M isotype plasma levels are influenced by interleukin-1alpha genotype.

    PubMed

    Kilpinen, S; Laine, S; Hulkkonen, J; Hurme, M

    2003-03-01

    The immunoglobulin (Ig) plasma levels are known to be, at least partially, genetically regulated, but all the genes involved are not known. Interleukin-1 (IL-1) is a potent proinflammatory cytokine able to serve as an adjuvant for immune responses. IL-1alpha gene is polymorphic, and at least one of the polymorphisms has been identified in the 5' regulatory region of the promoter, a biallelic base exchange (C-->T) at position -889. We set out to study whether the IL-1alpha genotype might contribute to the genetic component seen in the steady-state antibody levels of healthy individuals. Four hundred healthy blood donors (218 males and 182 females) were genotyped, and the plasma levels of IgM, IgG as well as IgG subclasses were measured. An association was found between IgG3 plasma levels and the IL-1alpha genotype; the 1.1 homozygotes had increased IgG3 levels compared with the 1.2 heterozygotes (P < 0.001 in males and P = 0.04 in females, Mann-Whitney U-test). A similar significant association was also found between IgM plasma levels and the IL-1alpha genotype in males, but it was no longer present in females; the 1.1 homozygotes had higher IgM levels than the 2.2 homozygotes (P = 0.03, Mann-Whitney U-test). The data suggest that IL-1alpha-mediated signals are critical for IgG3 and IgM responses, which are induced by thymus-independent antigens and are important in activating complement. PMID:12641660

  19. A Role for PCNA Ubiquitination in Immunoglobulin Hypermutation

    PubMed Central

    Arakawa, Hiroshi; Moldovan, George-Lucian; Saribasak, Huseyin; Saribasak, Nesibe Nur; Jentsch, Stefan; Buerstedde, Jean-Marie

    2006-01-01

    Proliferating cell nuclear antigen (PCNA) is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNAK164R mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases. PMID:17105346

  20. [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. PMID:26826992

  1. Intravenous Immunoglobulin in the Management of Lupus Nephritis

    PubMed Central

    Wenderfer, Scott E.; Thacker, Trisha

    2012-01-01

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

  2. Interaction between glycosaminoglycans and immunoglobulin light chains.

    SciTech Connect

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

    1997-01-01

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

  3. 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. PMID:18804488

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

    PubMed Central

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

    2016-01-01

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

  5. Alpha chain disease: immunoglobulin abnormalities, pathogenesis and current concepts.

    PubMed Central

    Seligmann, M.

    1975-01-01

    The laboratory findings upon which the diagnosis of alpha chain disease relies and the main results of immunochemical, structural and biosynthetic studies of the pathological immunoglobulin are reviewed briefly. The pathogenesis of the disease is discussed in view of its possibly non-malignant nature at the early stage and of its peculiar geographic distribution, suggesting the triggering role of an intestinal micro-organism. PMID:810152

  6. Treatment of multifocal motor neuropathy with intravenous immunoglobulin.

    PubMed

    Koski, Carol Lee

    2014-07-01

    Multifocal motor neuropathy (MMN) is a rare inflammatory, chronically progressive, unremitting disorder affecting the peripheral nervous system. Although the etiology of this condition is not known, high titers of IgM Ab to GM1 may serve as a biomarker for this disease. Clinical findings of motor weakness are associated with focal conduction blocks and with time, axonal destruction. Evidence supporting an immune etiology as well as the use of intravenous immunoglobulin to limit the disease progression is reviewed. PMID:24699885

  7. Phylogenetic diversification of immunoglobulin genes and the antibody repertoire.

    PubMed

    Litman, G W; Rast, J P; Shamblott, M J; Haire, R N; Hulst, M; Roess, W; Litman, R T; Hinds-Frey, K R; Zilch, A; Amemiya, C T

    1993-01-01

    Immunoglobulins are encoded by a large multigene system that undergoes somatic rearrangement and additional genetic change during the development of immunoglobulin-producing cells. Inducible antibody and antibody-like responses are found in all vertebrates. However, immunoglobulin possessing disulfide-bonded heavy and light chains and domain-type organization has been described only in representatives of the jawed vertebrates. High degrees of nucleotide and predicted amino acid sequence identity are evident when the segmental elements that constitute the immunoglobulin gene loci in phylogenetically divergent vertebrates are compared. However, the organization of gene loci and the manner in which the independent elements recombine (and diversify) vary markedly among different taxa. One striking pattern of gene organization is the "cluster type" that appears to be restricted to the chondrichthyes (cartilaginous fishes) and limits segmental rearrangement to closely linked elements. This type of gene organization is associated with both heavy- and light-chain gene loci. In some cases, the clusters are "joined" or "partially joined" in the germ line, in effect predetermining or partially predetermining, respectively, the encoded specificities (the assumption being that these are expressed) of the individual loci. By relating the sequences of transcribed gene products to their respective germ-line genes, it is evident that, in some cases, joined-type genes are expressed. This raises a question about the existence and/or nature of allelic exclusion in these species. The extensive variation in gene organization found throughout the vertebrate species may relate directly to the role of intersegmental (V<==>D<==>J) distances in the commitment of the individual antibody-producing cell to a particular genetic specificity. Thus, the evolution of this locus, perhaps more so than that of others, may reflect the interrelationships between genetic organization and function. PMID

  8. APOE genotype alters immunoglobulin subtypes in knock-in mice

    PubMed Central

    Zhou, Ye; Zhao, Wenjuan; Al-muhtasib, Nour; Rebeck, G. William

    2016-01-01

    Apolipoprotein E (APOE) alleles are strongly related to the risk of Alzheimer’s disease (AD). APOE genotype also affects inflammatory processes in response to damage. We tested whether APOE genotype affected the levels of specific immunoglobulins in healthy, uninfected APOE knock-in mice. We measured specific immunoglobulins in brain, spleen and plasma. Levels of total IgG in brain and spleen were highest in APOE-ε3 mice, significantly higher than in APOE-ε2 and APOE-ε4 mice; no differences were observed for levels of total IgG plasma. We also measured specific subtypes of IgG. IgG1 was only detectable in plasma, and did not differ by APOE genotype. IgG3 was detectable in plasma and spleen, and also did not differ by APOE genotype. IgG2b showed the same pattern as levels of total IgG by APOE genotype, with the highest levels of IgG2b in brain, spleen, and plasma of APOE-ε3 mice. IgG2a showed an entirely different pattern, with significantly higher levels in spleen and plasma of APOE-ε4 mice compared to APOE-ε2 and APOE-ε3 mice. We also measured IgM and IgA in spleens and plasma of these mice. In spleen, APOE-ε4 mice had the lowest IgA levels and the highest levels of IgM; both being significantly different from APOE-ε2 mice. In total, murine IgG2a and IgM were highest in APOE-ε4 mice, while total IgG and Ig2b were highest in APOE-ε3 mice. These dramatically different distributions of immunoglobulins could allow for human AD risk biomarkers based on specific immunoglobulin subtypes. PMID:25737044

  9. 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…

  10. The effects of corticosterone and cortisone on the uptake of polyvinyl pyrrolidone and the transmission of immunoglobulin G by the small intestine in young rats.

    PubMed Central

    Morris, B; Morris, R

    1976-01-01

    1. The distribution of polyvinyl pyrrolidone along the intestinal lumen and in the intestinal wall, following oral administration to normal and corticosterone treated rats, was found to be extremely variable. Valid comparisons between the two groups of animals could not be made using this technique. 2. Three, 4 and 5 days after corticosterone treatment there was no significant change in the uptake of 125I-labelled polyvinyl pyrrolidone from standard doses injected into ligated segments of the distal small intestine; nor did the treatment induce precocious replacement of the absorptive cells in this region. Cortisone induced precocious cell replacement, a process which took up to 4 days to complete, and also led to a marked reduction in the uptake of 125I-labelled polyvinyl pyrrolidone from ligated segments of the distal intestine. 3. Three days after treatment with corticosterone (5 mg I.P. at 12 days) there was a marked reduction of labelled immunoglobulin G transport into the blood. Four and 5 days after treatment there was some recovery of the immunoglobulin G transport function. Three days after treatment with cortisone (5 mg I.P. at 12 days) there was closure of the gut to labelled immunoglobulin G. 4. The relevance of these results to antibody transmission and the termination of immunoglobulin transport is discussed. PMID:1249782

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

    PubMed

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

    2016-01-01

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

  12. 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

  13. [Intranasal administration of immunoglobulins--perspectives for use in medical practice].

    PubMed

    Novikova, L I; Aleshkin, V A; Borisova, I V; Zueva, M M

    2008-01-01

    Effectiveness of topical use of immunoglobulines in respiratory infections along with preparations for parenteral use is discussed. Immunoglobuline preparations for intranasal use (drops, spays, aerosols) should take place among preparations intended for prevention and treatment of influenza, parainfluenza, respiratory syncitial virus infection and others. Potential to intranasal use of complex immunoglobulin preparation containing polymeric and monomeric antibodies of different isotypes is also discussed. PMID:19004281

  14. 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

  15. 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

  16. [Segmental testicular infarction. Unusual complication of intravenous immunoglobulin therapy for multifocal motor neuropathy].

    PubMed

    Rüb, J; Rehmann, R; von Landenberg, N; Roghmann, F; Stude, P; Tegenthoff, M; Noldus, J; Pastor, J

    2015-10-01

    We describe the previously unknown case of segmental testicular infarction as an iatrogenic complication of intravenous immunoglobulin administration in a patient with multifocal motor neuropathy. PMID:26303740

  17. Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis?

    PubMed

    Mose, S; Adamietz, I A; Saran, F; Thilmann, C; Heyd, R; Knecht, R; Böttcher, H D

    1997-08-01

    Therapeutic application of immunoglobulin is reported to be successful in radiation-induced oral and oropharyngeal mucositis. In this study the efficacy of prophylactic application of immunoglobulin was investigated. In 42 patients with head and neck cancer, postoperative radiation treatment or radiation combined with chemotherapy was performed. In 20 consecutive patients, prophylactic mucositis treatment consisted of panthenol (4 x 10 ml/day) and nystatin (4 x 1 ml/day). The 22 following patients received, supplementary to panthenol and nystatin, 800 mg (5 ml) human immunoglobulin intramuscularly once weekly. During the treatment time, the degree of mucositis was examined 3 times a week. The distribution of maximal mucositis degree revealed slightly more severe mucous membrane reaction in the control group compared with the immunoglobulin group (n.s.). The analysis of mean mucositis degrees in both groups demonstrated statistically significant differences (t test, p = 0.031) related to the entire group (n = 42) and to those 16 patients receiving radiation combined with chemotherapy. There was no significant immunoglobulin-induced effect on mucositis in patients treated by radiation alone. The time from the beginning of therapy to the first interruption could be prolonged 5 days in the immunoglobulin group (n.s.). In conclusion, it is demonstrated that the prophylactic application of immunoglobulin seems to lower the degree of radiation-induced mucositis. In comparison to the published data about therapeutically given immunoglobulin, the clinical efficacy of the prophylactic application of immunoglobulin as it is performed in this study is less evident. PMID:9256900

  18. 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)....

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

    PubMed

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

    2016-01-01

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

  20. Efficacy of Topical Immunoglobulins against Experimental Adenoviral Ocular Infection

    PubMed Central

    Nwanegbo, Edward C.; Romanowski, Eric G.; Gordon, Y. Jerold; Gambotto, Andrea

    2007-01-01

    Purpose Presently, there is no U.S. Federal Drug Administration (FDA)–approved antiviral therapy for the treatment of adenoviral (Ad) ocular infections. The goal of the present study was to determine the antiviral efficacy of human immunoglobulin (Ig), a preparation of highly purified and concentrated immunoglobulin (IgG) antibodies isolated from a large pool of human plasma donors, in vitro and on acute Ad replication in the Ad5 New Zealand White (NZW) rabbit ocular model. Methods The antiviral activity of human Ig against multiple wild-type and human ocular isolates of adenovirus serotypes was investigated in vitro by using neutralizing assays in different human epithelial cell lines. In vivo bilateral topical ocular toxicity and antiviral efficacy were evaluated with established Ad5/NZW rabbit ocular models. In vivo Ig antiviral results were compared with those obtained with topical 0.5% cidofovir and saline. Results In three different epithelial cell lines, ≤6.25 mg/mL of the Ig neutralized several wild-type adenoviral serotypes that cause ocular infections. A dose of ≤10 mg/mL neutralized 88% of ocular isolates of the adenovirus serotypes. After treatment of infected animals, adenovirus-positive cultures per total cultures (days 1–14; P = 0.021), the duration of Ad5 shedding, (P = 0.008), and the mean combined ocular viral titer during the early (days 1–5; P = 0.0001) and the late (days 7–14; P = 0.013) phases of infection were significantly lower in Ig-treated animals than in saline-treated animals and were similar to those in cidofovir-treated animals. Conclusions Ig demonstrated antiviral properties against multiple adenoviral serotypes in vitro and in the Ad5/NZW rabbit ocular model. Further studies are needed to advance topical immunoglobulin for treatment and prophylaxis of ocular infections. PMID:17724203

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-12-01

    Cryptorchidism is a condition where a testis persists in the abdominal cavity. Thus, due to elevated temperature we may expect induction of aberrant immune reactions depending on genetic constitution of individual. This may be reflected by development of anti-sperm antibodies (ASA) in cryptorchid males. Also, natural killer (NK) cells which belong to innate immunity may control adaptive immunity. Therefore, the gene system encoding polymorphic NK cell immunoglobulin receptors (KIRs) has been studied. 109 prepubertal boys with cryptorchidism and 136 ethnically matched young male donors were selected to study NK cell KIRs. DNA was isolated using automatic Maxwell(®) system from the peripheral venous blood drawn onto anticoagulant. Olerup SSP KIR Genotyping kit including Taq polymerase was used for detection of KIR genes. Human leukocyte antigen-C (HLA-C) groups, C1 and C2 were established using a Olerup SSP KIR HLA Ligand kit. KIR2DL2 (killer immunoglobulin-like receptor two-domain long 2) and KIR2DS2 (killer immunoglobulin-like receptor two-domain short 2) genes were less frequent in patients than in control individuals (corrected p values: 0.0110 and 0.0383, respectively). However, no significant differences were observed between ASA-positive and ASA-negative patients, or between bilateral or unilateral cryptorchidism. No association between KIR ligands C1 and C2, alone or together with KIR2DL2, was found. However, the results suggest that KIR2DL2+/KIR2DS2+ genotype may be, to some extent, protective against cryptorchidism. PMID:26679162

  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. PMID:26831168

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2015-12-01

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

  6. 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

  7. Formation of slow-reacting substance by guinea pig immunoglobulins.

    PubMed Central

    Jancar, S.; Akimura, O. K.; Dias da Silva, W.

    1976-01-01

    The capacity of guinea pig antibodies to mediate the antigen-induced release of slow-reacting substance (SRS) in the rat peritoneal cavity is restricted to IgG2 and, to a lesser extent, to IgG1 populations of immunoglobulin. IgM and homocytotropic antibody of the reaginic type lacked this activity. The process was partially blocked by previous decomplementation of the rats, was not affected by previous reduction of the circulating leukocytes, and was partially suppressed by previous depletion of circulating platelets with an antiserum to rat platelets. PMID:11696

  8. Serum Immunoglobulins in Newborn Calves Before and After Colostrum Feeding

    PubMed Central

    Merriman, Mohendra J. G. S.

    1971-01-01

    Pre-colostral and post-colostral sera of seven Holstein calves and colostral whey were analyzed immunoelectrophoretically. IgM, IgG1 (fast), and IgG2 (slow) were demonstrated while IgA was not detected in serum of new-born calves before colostrum feeding. In post-colostral serum IgG, IgM, in relatively higher levels, and IgA were present which corresponded with the classes of immunoglobulins found in whey. These observations suggest that the developing bovine fetus may be capable of independent immune response. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4. PMID:4260939

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

    PubMed

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

    2002-09-01

    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. PMID:12088642

  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