Rheumatoid Factor and Immune Networks

Section: Discussionmentioning

confidence: 99%

“…Therefore, the simple assignment of a heavy-chain gene to this family does not necessarily demonstrate a functional relationship of the encoded antibodies with other members of the same family. A comprehensive computer search revealed no homology to known RF heavy-chain genes (33).…”

Section: Discussionmentioning

confidence: 99%

The antigen-binding domain of a human IgG-anti-F(ab′)₂ autoantibody

Welschof

Terness

Kipriyanov

et al. 1997

“…The production of antibodies themselves is regulated in part by autoimmune responses to defined portions of the antibodies, most notably combining site-related markers or idiotypes (5,6) and constant-region markers detected by IgM antibodies termed rheumatoid factors (7). Because of the crucial importance of immunoglobulin-like T-cell receptors (TCRs) in the initiation of specific immunity, we chose to focus on natural human antibodies to synthetic peptides based on human TCR /3-chain gene sequence.…”

mentioning

confidence: 99%

Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain.

Marchalonis

Kaymaz

Dedeoğlu

et al. 1992

172

119

We used mapping with synthetic overlapping peptides in combination with molecular modeling to analyze the IgG antibodies that humans naturally produce against human T-cell receptor .8 chains and to localize the recognized peptide autoantigens in the three-dimensional structure of the molecule. Healthy individuals produce low levels of antibodies against T-cell receptor peptides, and these can be increased in autoimmune diseases. We characterized the reactivities in detail because IgG molecules reactive with self peptides occur in preparations of intravenous immunoglobulin and can be isolated by immunoaffinity chromatography. Natural IgG antibodies were directed against three major peptides. One corresponds to the first complementarity-determining region of the variable region. A second corresponds to the third framework of the variable region. The third is located in the constant region and is predicted to be a loop that extends out of the 18-barrel structure. This peptide is one that would give a characteristic structural distinction between the fl-chain constant region and the constant regions of immunoglobulin light chains to which 13 chains are homologous. The capacity to bind these peptides is found in small fractions of normal polyclonal IgG, which contains both Kc chains and A chains. The activity is antibody-like in being confined to the Fab fragment and in its capacity to discriminate among homologous synthetic peptides corresponding to distinct f-chain variable-region genes.We propose that a recognition and regulatory process naturally occurs that parallels the immune network for the regulation of the production of antibodies.Humans produce antibodies to a variety of self antigens without noticeable ill effects (1-4). The production of antibodies themselves is regulated in part by autoimmune responses to defined portions of the antibodies, most notably combining site-related markers or idiotypes (5, 6) and constant-region markers detected by IgM antibodies termed rheumatoid factors (7). Because of the crucial importance of immunoglobulin-like T-cell receptors (TCRs) in the initiation of specific immunity, we chose to focus on natural human antibodies to synthetic peptides based on human TCR /3-chain gene sequence. We assessed by enzyme-linked immunosorbent assay (ELISA) the capacity ofsera to react with synthetic TCR peptide autoantigens. These sera were obtained from ostensibly healthy individuals 20-90 years of age and from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Hexadecapeptides representing the TCR YT35 ,3 chain, which contains V,8, D1.1, J01.2, and Cp1 segments (8), were overlapped by 5 residues to model the antigenic structures (9, 10) of the TCR P fragment homologous to immunoglobulin A light chain (11).We found that reaction of human IgG with particular synthetic TCR autoantigens occurs in low levels in healthy individuals and can rise in autoimmune diseases such as RA. We present immunochemical data characterizing the nature and locations of the T...

“…Hybridization of BamHI-digested DNAs from different individuals with hv3005/E1.6 displayed five major restriction fragment length polymorphism (RFLP) patterns, defined by either the presence or absence ofhybridizing bands at the 6-kb/1.9111 region and the 5.2-kb/hv3005 region, and by the intensity of each hybridizing band, which reflects homozygosity or heterozygosity for the respective locus. Thus, there are 9 potential RFLP phenotypes: (6,6,5,5), (6,6,5,0), (6,6,0,0), (6,0,0,0), (6,0,5,5), (6,0,5,0), (0,0,5,5), (0,0,5,0), and (0,0,0,0). Among the initial 34 unrelated individuals studied, the major (6,6,5,O) type accounted for 50% of the observed genotypes, whereas the (6,6,5,5), (6,6,0,0), (6,0,5,0), (6,0,5,5), and (0,0,5,5) types each accounted for 18%, 15%, 12%, 6%, and 6%, respectively (27).…”

Section: Resultsmentioning

confidence: 99%

“…Autoantibodies are the hallmarks of systemic autoimmune diseases and may contribute to tissue damage (4,5). However, certain autoantibodies, such as those against nucleic acids and against IgG (rheumatoid factor, RF), are also found in a low concentration in the serum of healthy individuals and may serve some physiological functions (6)(7)(8)(9).…”

mentioning

confidence: 99%

Possible deletion of a developmentally regulated heavy-chain variable region gene in autoimmune diseases.

Yang

Olsen

Siminovitch

et al. 1990

Self Cite

Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. We have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e., Humhv3005/Pl) related to both anti-DNA and anti-IgG autoantibodies, we studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (VH) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important VH genes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.