Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The BLA cross-idiotype (XId) is present on a unique subset of rheumatoid factors (RF) that cross-react with DNA-histone. In this study, prototype Bla monoclonal RF was shown from serologic investigations and N-terminal amino acid sequence analysis to have distinct kappa chains related to the V kappa III subgroup and VH4 heavy chains. The amino terminus of the heavy chain was cyclized, rendering the protein resistant to Edman degradation and providing a possible investigator bias to the published Ig sequence data to date. This appears to be the first definitive report of a serum IgM that expresses the VH4 gene. RF with DNA cross-reactivity have been reported to be produced by human and mouse cloned cells that have the VH4 or homologous mouse Vh36-60 gene.
Arthritis Rheum 1990 Nov
PMID:Human rheumatoid factor cross-idiotypes. III. Bla monoclonal rheumatoid factor, prototype of the BLA cross-idiotype group, has distinct kappa chains related to the V kappa III subgroup and VH4 heavy chains. 190 41

HLA-B*2705 transgenic mice were continuously backcrossed to mice of the B10 background with various haplotypes. A high level of expression of the HLA-B27 protein was detected on peripheral blood lymphocytes (PBLs) from mice homozygous for H-2b, H-2f, H-2s, H-2p, H-2r, and H-2k haplotypes by FACS analysis with the ME-1 antibody. A lower level of expression of B27 was observed on PBLs from H-2v mice. Little or no expression of B27 was detected on PBLs from H-2 or H-2d mice. We hypothesize that the HLA-B27 heavy chain is analogous to and competes with endogenous class I heavy chains in the H-2d, H-2q and H-2v haplotypes. Interestingly, other studies in our laboratory have demonstrated that mice with the H-2d and H-2q haplotypes with deletions of certain T cell receptor subsets are more prone to Yersinia-induced arthritis (YIA). Therefore, the mouse model of YIA may provide insights into the mechanisms of HLA-B27-linked spondyloarthropathies in man.
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PMID:Effect of H-2 genes on expression of HLA-B27 and Yersinia-induced arthritis. 225 92

Molecular characterization of rheumatoid factors (RF) in rheumatoid arthritis (RA) has been hampered because of their polyclonality. To overcome this problem, we generated monoclonal RF-secreting hybridomas from rheumatoid synovial cells. Among the RF-secreting hybridomas, HAF10 secreted an IgM-RF that was monospecific for human IgG. It bound well to IgG1 and IgG2, but not to IgG3 and IgG4. Sequence analysis of its heavy and light chains showed that it contained a VH1 heavy chain and a V lambda light chain that did not belong to any known lambda light chain subgroup, and therefore, probably represented a new lambda subgroup. These results indicated that both the heavy and light chains of a monoclonal IgM-RF from rheumatoid synovial cells were quite different from the reported variable region sequences of several monoclonal RF derived mainly from patients with mixed cryoglobulinemia. Further studies of additional monoclonal RF from RA patients are warranted to define precisely their genetic basis and to further our understanding of the immunopathology of RA.
Arthritis Rheum 1990 Aug
PMID:Serologic and molecular characterization of a human monoclonal rheumatoid factor derived from rheumatoid synovial cells. 239 Jan 24

Two-hundred twenty-four hybridomas secreting monoclonal IgM rheumatoid factor (hIgMRF) derived from MRL-lpr/lpr, MRL-+/+ and C57BL/6-lpr/lpr autoimmune mice were analyzed with regard to IgG subclass and domain specificity, and some for VH gene expression patterns. Among these mice, only MRL-lpr/lpr develop arthritis. Clonotypes specific for each of the four mouse IgG subclasses and clonotypes reacting with more than one IgG subclass were identified. Although each panel contained several clonotypes, the predominant one differed in each strain (MRL-lpr/lpr, anti-IgG2a; MRL-+/+, combined anti-IgG2a and 2b; C57BL/6-lpr/lpr, anti-IgG1 or combined anti-IgG1, 2a, and 3). The IgG domains recognized by these monoclonals were defined with mutant Ig carrying IgG1 heavy chains that lacked either the CH1 or CH3 domains, variant Ig carrying hybrid IgG2b-2a heavy chains, and IgG fragments. Inhibition of hIgMRF binding to IgG substrates by protein A was also assessed. Most determinants were assigned to the CH3 domain, but determinants in the hinge region, CH2 domain, and in some instances, even in the Fab portion, could also be identified. Hybridization of cytoplasmic RNA from 35 classes of diverse IgG subclass specificity with VH gene probes representing seven of the approximately 10 VH families (7183, S107, Q52, J558, J606, 36-60, X24) indicated that approximately 90% of these clones expressed VH genes belonging to the large J558 gene family. The results indicate that murine IgMRF are extremely heterogeneous in IgG subclass and domain specificities; the genetic background influences RF specificity characteristics that may relate to pathogenicity; and considering the complexity of the J558 VH gene family and reported RF heavy chain assignments to additional VH gene families, it appears that VH genes encoding RF are diverse.
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PMID:Specificity and molecular characteristics of monoclonal IgM rheumatoid factors from arthritic and non-arthritic mice. 244 Sep 45

Recently, the heavy chain of 16/6 idiotype-positive human anti-DNA antibodies was found to be similar, but not identical, to the VH26 gene. We resequenced the VH26 gene and found that its coding sequence is actually identical to the complementary DNA sequence of the anti-DNA antibodies previously described. Together with the previous data, our findings demonstrate that some human autoantibodies are encoded directly by immunoglobulin V region genes, and that these V region genes are remarkably conserved in populations.
Arthritis Rheum 1988 Nov
PMID:A 16/6 idiotype-positive anti-DNA antibody is encoded by a conserved VH gene with no somatic mutation. 326 66

We studied cardiac tissues of a patient who died of severe rheumatic myocarditis. Multiple Aschoff lesions were present throughout both ventricles and auricles. Immunofluorescence studies showed large monocytoid cells staining with OKM1 and anti-Leu M-3 as well as anti-Ia. Scattered T cells in areas of focal myocarditis stained with OKT3. Parallel staining for cardiac myosin-heavy chain antigens showed patchy dissolution of cardiac muscle fibers and traces of cardiac myosin within large monocytoid Aschoff cells.
Arthritis Rheum 1986 Feb
PMID:Immunofluorescence studies of florid rheumatic Aschoff lesions. 351 70

Evidence is presented that the development of arthritis induced in mice by 2,6,10,14-tetramethylpentadecane (pristane) involves the immune response. Mice irradiated (500 rad) before injection of pristane failed to develop arthritis. By contrast, irradiated mice given lymphoid cells from normal donors and challenged with pristane developed arthritis. Other experiments showed that lymphoid cells from irradiated mice given pristane suppressed the development of arthritis in recipients challenged with pristane. Finally, the incidence of arthritis was significantly higher in CBA/Igb mice given pristane than in the allotypic congenic strain CBA/H, suggesting that a gene linked to the heavy chain immunoglobulin locus controls the development of arthritis.
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PMID:Immunological involvement in the pathogenesis of pristane-induced arthritis. 355 94

Lymphocytotoxic activity of sera from systemic lupus erythematosus (SLE) patients and their families was inhibited by 50% or more by preincubation of target cells with Fab2 fragments of xenoantisera against beta 2 microglobulin or the heavy chain of the HLA-A,B,C antigenic molecular complex. An antiHLA-DR xenoantiserum had less blocking effect on peripheral blood mononuclear cells but was effective at blocking reactivity of these sera against cultured B lymphoid cell lines. The repertoire of specificities in family members' sera differed from each other and their respective proband with respect to their reactions with cultured lymphoid cell lines. These data indicate that lymphocytotoxic antibodies (LCA) found in most patients with SLE and some of their relatives include a subpopulation with specificity for determinants present on major histocompatibility gene products. They also suggest that LCA in relatives represent a defect in immune regulation which allows expression of existing autoimmune potentials rather than immunization with a single "lupus" antigen.
Arthritis Rheum 1980 Mar
PMID:Lymphocytotoxic antibodies in systemic lupus erythematosus patients and their relatives: reactivity with the HLA antigenic molecular complex. 615 98

Autoantibodies specific for type-II collagen (CII) occur in mice and rats with collagen-induced arthritis (CIA). The binding in vitro and in vivo of mouse monoclonal antibodies (MoAbs) specific for separate epitopes in CII have been investigated. Two-day-old mice were injected intraperitoneally (i.p.) with the anti-CII antibody CIID3 in both unlabelled and biotinylated form. It was found that antibodies binding to the same epitope in CII in vivo can inhibit others from binding in an epitope-specific fashion. The binding in vivo and in vitro of anti-CII antibodies could be inhibited also by an anti-idiotypic rat antiserum produced against the D3 antibody. The anti-idiotypic antiserum inhibited the binding of the antibody D3 and the idiotypically related antibody C2. The cDNA's of anti-CII antibodies D3, C2, and F4 were sequenced and found to contain germline encoded V-genes, apparently without somatic mutations. The variable heavy chain of D3 and C2 both expressed the same VH rearrangement, confirming that they share idiotypes. This report demonstrates that CII-specific germline-encoded IgG autoantibodies bind specifically to normal cartilage in vivo via their combining site.
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PMID:Germline-encoded IgG antibodies bind mouse cartilage in vivo: epitope- and idiotype-specific binding and inhibition. 750 97

We previously showed that serum-derived 85-kDa proteins (SHAPs, serum-derived hyaluronan associated proteins) are firmly bound to hyaluronan (HA) synthesized by cultured fibroblasts. SHAPs were then identified to be the heavy chains of inter-alpha-trypsin inhibitor (ITI) (Huang, L., Yoneda, M., and Kimata, K. (1993) J. Biol. Chem. 268, 26725-26730). In this study, the SHAP.HA complex was isolated from pathological synovial fluid from human arthritis patients. The SHAP.HA complex was digested with thermolysin, followed by CsCl gradient centrifugation. The HA-containing fragments thus obtained were further digested with chondroitinase AC II and subjected to TSK gel high performance liquid chromatography (HPLC). Peptide-HA disaccharide-containing fractions (the SHAP.HA binding regions) were further purified by reverse phase HPLC. Major peaks were analyzed by protein sequencing and mass spectrometry (electrospray ionization mass spectrometry and collision induced dissociation-MS/MS). By comparison with the reported C-terminal sequences of the human ITI family, the peptides were found to correspond to tetrapeptides derived from the C termini of heavy chains 1 of and 2 of inter-alpha-trypsin inhibitor (HC1 and HC2), and heavy chain 3 of pre-alpha-trypsin inhibitor (HC3), respectively, and a heptapeptide from HC1. Mass spectrometric analyses suggested that the C-terminal Asp of each heavy chain was esterified to the C6-hydroxyl group of an internal N-acetylglucosamine of HA chain. This report is the first demonstration to give evidence for the covalent binding of proteins to HA.
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PMID:Evidence for the covalent binding of SHAP, heavy chains of inter-alpha-trypsin inhibitor, to hyaluronan. 759 91


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