Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lymphocytes from patients with rheumatoid arthritis (RA) show an abnormal response after stimulation with Epstein-Barr virus (EBV), a potent B cell mitogen. In vitro IgM production from EBV stimulated lymphocytes was measured over a 21 day period. In keeping with previous studies, RA lymphocytes showed increasing IgM production between 14 and 21 days, whereas IgM production decreased during this period in normal lymphocytes (p less than 0.001). Experiments on 12 HLA identical, RA discordant sibling pairs were also undertaken. B enriched and T enriched lymphocyte populations were obtained and recombined in both an autologous and homologous manner. The abnormality in IgM production in patients with RA was shown to reside in the RA T cell population (p less than 0.005), and RA B cells combined with normal T cells behaved similarly to autologous cultures of normal B and T cells. The study shows that impaired immunoregulation of EBV stimulated B cells in RA is secondary to a functional defect in RA T cells, but no difference in the concentration of T suppressor/cytotoxic cells could be found between the disease discordant siblings. The abnormality in immunoregulation appears to be secondary to RA, rather than a product of genes encoded within the major histocompatibility complex (MHC) region, as defined by HLA-DR, A, B, and C typing.
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PMID:Demonstration of impaired T cell regulation of Epstein-Barr virus stimulated B lymphocytes in rheumatoid arthritis with HLA identical, disease discordant sibling pairs. 283 21

Genes of the major histocompatibility complex, HLA, are associated with susceptibility to rheumatoid arthritis (RA), but the aetiology of this chronic inflammatory disease is not known. Synthetic oligonucleotide DNA probes were constructed to distinguish between two closely related but distinct alleles encoding the HLA-DR4 specificity in patients with RA. With these allele-specific oligonucleotide probes an uncommon DR4 genetic variant, Dw14, was identified in 6 of 7 RA patients homozygous for HLA-DR4. This allele may play an important part in susceptibility to RA.
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PMID:Identification of HLA-Dw14 genes in DR4+ rheumatoid arthritis. 287 72

Considerable evidence indicates that genes residing within the major histocompatibility complex (MHC) influence susceptibility to certain rheumatic diseases, such as ankylosing spondylitis (AS) and rheumatoid arthritis (RA). However, it has not yet been possible to precisely identify the gene(s) responsible for conferring enhanced susceptibility to these diseases. The availability of recombinant DNA technology should accelerate progress in obtaining this goal. A particularly promising method in this regard is restriction fragment length polymorphism (RFLP) analysis using appropriate class I and class II MHC gene probes. In preliminary studies, RFLPs have been identified for AS and RA which associate with susceptibility to the disease. Further studies using this approach should permit localization and precise identification of the disease susceptibility gene(s) for these diseases.
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PMID:Analysis of restriction fragment length polymorphisms in rheumatic diseases. 289 32

Bam HI DR-beta and DQ-beta restriction fragment length polymorphisms (RFLPs) were found with increased frequency in white persons with seropositive rheumatoid arthritis as compared with control subjects. DR-beta 4.8-, 5.2-, and 7.0-kilobase (kb) RFLPs were observed in 86.5 percent of rheumatoid arthritis patients and in 56 percent of control subjects (p = 0.001, relative risk [RR] = 5.0). The 6.0-kb RFLP was present in 79 percent of rheumatoid arthritis patients and 32 percent of control subjects (p = 0.0002, RR = 8.0). The 4.8-, 5.2-, and 7.0-kb RFLPs correlated with DR4, -7, -9, and -w53 phenotypes and the 6.0-kb RFLP correlated only with DR4. Thus, these RFLPs do not appear to be disease-specific. A DQ-beta 3.2-kb RFLP was found in 63.5 percent of rheumatoid arthritis patients and in 38.0 percent of control subjects (p = 0.01, RR = 2.8). This fragment was frequently found in persons expressing DR1 and DQw1 phenotypes. Probes consisting of the first exon of the DR-beta-I and DR-beta-IV genes, respectively, only hybridized with the 5.2- and 6.0-kb RFLPs. These data suggest that more than one gene within the major histocompatibility complex contributes to susceptibility to seropositive rheumatoid arthritis in white persons.
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PMID:Molecular genetic studies of rheumatoid arthritis. 290 61

The DR1 and DRw10 beta 1 chain genes were isolated from each of 2 individuals with rheumatoid arthritis who were heterozygous for these class II major histocompatibility complex specificities. The sequences of the DR1 beta 1 chains from both patients were identical, differing from previously reported DR beta 1 chains of individuals without RA by 2 amino acid substitutions, at positions 85 (Val-Ala) and 86 (Gly-Val), and by a silent mutation at the last nucleotide of codon 78 (C-T), resulting in the loss of a Pst I restriction endonuclease site. Identical DRw10 beta 1 chain genes were found in both patients. These were shown to encode the epitope recognized by monoclonal antibody 109d6. This antibody also recognizes an epitope on the DRw53 beta 2 chain of the DR4 haplotype. The third diversity regions of the DR1 beta (amino acids 67-74) and the DRw10 beta 1 chains (amino acids 67-73) were identical, respectively, with those of the DR4 (Dw14) beta 1 and beta 2 chains, raising the possibility that in these patients, the third diversity regions of the two DR beta 1 chain genes present in trans are conformationally equivalent to the cis-encoded third diversity regions of the DR4 (Dw14), DR beta 1, and beta 2 chains. The nucleotide sequences of the DQ beta complementary DNA clones were identical to that of the DQw1 beta chain, and no DR beta 2 complementary DNA clones were identified.
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PMID:Class II major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DR beta 1 genes in two DR1, DRw10-positive individuals specify the same inferred amino acid sequence as the DR beta 1 and DR beta 2 genes of a DR4 (Dw14) haplotype. 293 Jun

Proliferation of rheumatoid and control peripheral blood mononuclear cells to OKT3, phorbol myristic acid (PMA), phytohemagglutinin (PHA), tuberculin PPD and in the autologous mixed lymphocyte reaction (AMLR) was investigated. Only the responses to PPD and in the AMLR were depressed. This was not due to suppression by OKT8 lymphocytes. The proportion of antigen responsive (T4+ 4B4+) cells was normal but suppressor-inducer (T4+ 2H4+) cells were decreased. The depressed response was not completely restored by addition of recombinant interleukin-2. We propose that a basic defect in rheumatoid arthritis resides in T lymphocytes which react to self-major histocompatibility complex antigens either on their own, as in the AMLR, or as restriction elements in the presentations of soluble antigen.
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PMID:Abnormal lymphocyte reactivity to self-major histocompatibility antigens in rheumatoid arthritis. 295 72

Dendritic cells (DC) were isolated from synovial tissue and synovial fluids of patients with rheumatoid arthritis and from peripheral blood of healthy donors. The cells were analysed for various surface antigens in indirect immunofluorescence by means of monoclonal antibodies. Surface antigen expression and accessory activity of the DC during short-term cultures were also investigated. Both the rheumatoid synovial and the normal blood DC were strongly positive for panleucocyte antigen and class II major histocompatibility complex (MHC) antigens (HLA-DP, HLA-DQ, and HLA-DR). The DC suspensions (purity approximately 80-85%) showed very low percentage of cells staining for various other cell membrane markers, including B cell, T cell, natural killer (NK) cell, and various monocyte/macrophage markers as well as markers specific for dendritic reticulum cells and Reed Sternberg cells. Moreover, neither rheumatoid nor normal DC reacted with the RFD1 monoclonal antibody, which is specific for interdigitating cells of human thymus. In contrast to Langerhans' cells, the DC lacked the thymocyte (T6) marker. The various DC expressed neither complement receptors (CR1, CR3), transferrin receptors, nor Fc receptors. They also lacked enzyme markers like peroxidase and nonspecific esterase. The DC formed clusters with autologous T cells. Cluster formation was readily inhibited by anti-HLA-DR and anti-CD2 (T11) monoclonal antibodies. After 3 to 5 days in culture the DC still expressed class II MHC antigens and were potent stimulators in allogeneic mixed lymphocyte reactions (MLR). Only a small number of cells in the DC suspensions from synovial tissue expressed fibroblast antigens before and after culture.
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PMID:Characteristics of human rheumatoid synovial and normal blood dendritic cells. Retention of class II major histocompatibility complex antigens and accessory function after short-term culture. 296 Oct 51

Gold salt therapy-induced pneumonitis is a rare complication in patients with rheumatoid arthritis (RA). We studied HLA-A, B, C, D/DR, and complement factor B (Bf) and C4 alleles in 17 patients with RA and gold-induced pneumonitis and found that these patients had strikingly homogeneous major histocompatibility complex (MHC) markers. Eight of them (47 percent) had the alleles HLA-A3 B35 Dwl BfF C4A3,2 (BO), which were shown by family studies of some patients to be inherited as an extended MHC-haplotype with an apparent gene duplication in the C4A locus. The other high-risk phenotype, HLA-B40 with a C4 null allele, was found in eight patients (47 percent). All but three of the 17 patients had at least one of the two high-risk markers, the frequency of these combinations being clearly higher than in the two control groups: patients with RA but with no gold-induced side effects and healthy individuals. Our study shows that use of several MHC markers together results in a strong association between the markers and the disease.
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PMID:Patients with rheumatoid arthritis and gold-induced pneumonitis express two high-risk major histocompatibility complex patterns. 311 96

In a prospective 24 week study of 25 patients with rheumatoid arthritis (RA) weekly intramuscular (IM) sodium aurothiomalate resulted in a small but significant reduction in the circulating lymphocyte count. Analysis of absolute levels of pan T cells, T4 helper cells, T8 suppressor cells, T4/8 ratio, B cells, and major histocompatibility complex (MHC) class II positive cells showed reductions in these subsets, though these changes did not reach significance. At entry there was no association between circulating lymphocyte counts and subsets and clinical and laboratory indices which reflected disease activity, and during the study gold responders could not be differentiated from non-responders with regard to changes in lymphocyte counts and subsets. Thus this study suggests that weekly IM gold leads to a modest reduction in circulating lymphocyte numbers which involves most subsets. This effect appears to be independent of the clinical efficacy of this drug.
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PMID:Effects of chrysotherapy on circulating lymphocyte numbers and subsets. 312 97

This is an interpretive review of recent immunologic and molecular biologic data concerning the molecular basis of susceptibility to rheumatoid arthritis. The central point of view was taken that the major histocompatibility complex (MHC) class II molecules encoding disease susceptibility function in an immune recognition event involving an antigen "X" that currently eludes characterization. The problem of understanding the meaning of the association of susceptibility with diverse MHC alleles such as DR4 (Dw4 and Dw14), DR1, and DRw10 is approached by detailed biochemical analysis that led to the identification of common stretches of amino acid sequence, presumably encoding conformationally equivalent structures. Non-classic MHC polymorphisms related to disease susceptibility but not associated with particular alleles such as identified by Ab 109d6 proved especially valuable in suggesting new directions for attempting to understand the significance of these associations. Consideration is given to the possibility that a family of either slightly different or identical conformations encoded in either cis or trans cumulatively confer the liability to develop rheumatoid arthritis, and implying a highly non-classic mode of inheritance. The available data do not permit a distinction between the possibilities that an antigen "X" was being presented to T cells or whether the distinctive conformations of the MHC class II molecule serve the same role as antigen "X" but are directly recognized by T cells. However, with additional data, some limited insight should be able to be inferred about the nature of an antigen "X" that specifically binds to the MHC conformation with a complementary interaction. It seems reasonable to consider the pathogenesis of rheumatoid arthritis as a typical immune response resulting from a simple immune recognition event of a single antigenic molecule.
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PMID:The molecular basis of susceptibility to rheumatoid arthritis: the conformational equivalence hypothesis. 314 68


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