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

Patients selected for the presence of scleroderma-related antibodies (anti-DNA-topoisomerase I [anti-topo I; n = 43], anticentromere antibody [ACA; n = 63], or anti-Pm-Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti-topo I was associated with HLA-DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti-Pm-Scl were positive for HLA-DR3 (versus 23.5% of controls; Pcorr less than 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr less than 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA-DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA-positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti-topo I and anti-Pm-Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody-defined scleroderma subsets.
 ...
PMID:Immunogenetic associations of scleroderma-related antinuclear antibodies. 234 21

Macrophages present in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) express large amounts of HLA-DR molecules on their surface, despite low levels of gamma-interferon (gamma-IFN) in the joint. To determine whether this apparent paradox is the result of increased sensitivity to gamma-IFN in RA, we compared concentrations of gamma-IFN that induced HLA-DR and DQ on peripheral blood monocytes of RA patients and normal donors, using fluorescence-activated cell sorter analysis. Among normal donors, highly variable sensitivity to gamma-IFN was observed. Higher amounts of gamma-IFN were required to induce class II major histocompatibility complex molecules on RA monocytes versus normal monocytes. The maximum amount of HLA-DR that could be induced on RA and normal monocytes was similar; however, peak levels of HLA-DQ were significantly less in RA. Monocytes from patients with other forms of chronic inflammatory arthritis had intermediate HLA-DQ expression after gamma-IFN treatment. These data suggest that an increased sensitivity to gamma-IFN in RA does not account for the high level of HLA-DR expression in the joint. Also, a defect in HLA-DQ and HLA-DR induction by gamma-IFN was observed.
 ...
PMID:Cytokines in chronic inflammatory arthritis. III. Rheumatoid arthritis monocytes are not unusually sensitive to gamma-interferon, but have defective gamma-interferon-mediated HLA-DQ and HLA-DR induction. 250 78

Type II collagen-induced arthritis (CIA) in mice is an autoimmune experimental model for rheumatoid arthritis. Susceptibility to CIA is associated with certain major histocompatibility complex class II haplotypes. The two very closely related haplotypes H-2q and H-2p differ in susceptibility to CIA. Only mice of H-2q (DBA/1, B10G strains) but not mice of H-2p-expressing strains (like strain B10P) develop CIA and an autoimmune response to type II collagen (CII) after immunization with CII. In contrast to H-2p, the H-2q haplotype does not express I-E molecules. The purpose of the present study was to identify, at the molecular level, the structures on major histocompatibility complex class II molecules determining susceptibility to CIA and CII responsiveness. We first excluded the possible suppressive involvement of Ep or Ap molecules by showing that F1 hybrids between H-2p and H-2q haplotype strains, expressing Ep and Ap, are responders to CII and fully susceptible to CIA. Secondly, because A alpha chains appear identical, we sequenced the A beta first-domain exons of p and q allotypes and found only four diverging amino acids in the predicted amino acid sequence. These variable residues were closely located at positions 85, 86, 88, and 89 at the end of the postulated alpha-helix, which is of importance for interactions with the antigenic peptide and the T-cell receptor. We suggest that this region is a critical major histocompatibility complex restriction site for CIA and CII responsiveness in H-2q mice as compared with H-2p mice. The CIA will now be an excellent autoimmune model for studies on interactions between autoantigenic peptide, autoreactive T cells, and a particular major histocompatibility complex molecule, as has been postulated to be the initial event also in rheumatoid arthritis.
 ...
PMID:Localization of a critical restriction site on the I-A beta chain that determines susceptibility to collagen-induced arthritis in mice. 251 82

The occurrence of the inappropriate immune response of rheumatoid arthritis is likely controlled by several alleles of class II DR beta chain genes of the major histocompatibility complex (MHC). These include certain of those that encode the serologically distinct DR1 and DR4 specificities. In a manner analogous to a segregation analysis, advantage was taken of ethnic differences in susceptibility associated with different alleles and parallel differences in the organization of the class II haplotypes that specify either similar or divergent serologic specificities. This permitted mapping of this disease susceptibility into a single equivalent polymorphic alpha helical conformation shared by each DR beta allelic product. This suggests that rheumatoid arthritis originates from a unitary immune recognition event initiated by particular class II MHC molecules.
 ...
PMID:Susceptibility to rheumatoid arthritis--the conformational equivalence hypothesis. 251 58

The majority of peripheral T cells express a heterodimeric, alpha/beta T-cell receptor, which recognizes specific antigenic peptides bound to self major histocompatibility complex (MHC) molecules, and either the CD4 or CD8 surface markers. An additional subset of T cells, whose physiological function is unknown, express a distinct CD3-associated receptor composed of gamma and delta chains. This subset includes cells lacking both CD4 and CD8 surface markers, which may be involved in autoimmunity. The recognition specificity of the gamma/delta receptors is not well characterized and has been defined in only one case to date, a murine cell line which shows MHC-linked specificity. In this report, we describe the isolation of CD4- CD8-, gamma/delta TCR bearing T cell clones from the synovial fluid of a rheumatoid arthritis patient. These T cell clones respond specifically to mycobacterial antigens without MHC restriction.
 ...
PMID:Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. 252 9

The contribution of genes within the major histocompatibility complex to rheumatoid arthritis has been calculated (Rotter & Landaw 1984). Separate data from hospital- and population-based studies of monozygotic twin concordance rates and sibling recurrence risks have been used, along with material from published haplotype-sharing studies. Using either source of information gives the same result, a contribution of 37%.
 ...
PMID:The contribution of HLA to rheumatoid arthritis. 267 68

Pristane was injected intraperitoneally into mice of several strains, inducing an inflammatory seropositive arthritis in susceptible strains. The evolving histologic features included synovial hyperplasia, periostitis, and progressive marginal erosions. Multiple serologic immune abnormalities, including rheumatoid factor and anticollagen antibodies, also developed. Genetic analysis indicated that the major histocompatibility complex (H-2), C5 hemolytic complement (Hc), Newcastle disease virus-induced interferon (IF-1), and athymic (nu/nu) loci were involved in regulating susceptibility to pristane-induce arthritis. This experimental murine disease may provide a novel model of rheumatoid arthritis.
 ...
PMID:Pristane-induced arthritis. The immunologic and genetic features of an experimental murine model of autoimmune disease. 276 2

We investigated cellular phenotypes and expression of class II major histocompatibility complex antigens on endothelium and cellular infiltrates in synovium from patients with rheumatoid arthritis (RA) or reactive arthritis, using an indirect immunoperoxidase technique. The RA specimens showed synovial lining layer hypertrophy and several focal accumulations of lymphocytes, both of which were absent in the reactive arthritis synovium. The percentage of cells expressing monocyte/macrophage markers was significantly higher in RA specimens. The percentages of cells expressing B and T cell markers were similar in both diseases. There was no significant difference in the expression of HLA-DR or DP by endothelium in the 2 diseases, but a marked increase in expression of HLA-DQ by endothelium was observed in the RA synovium versus that from patients with reactive arthritis. This overexpression of HLA-DQ was also seen in the interstitial cells of RA patients compared with reactive arthritis patients. In the reactive arthritis synovium, a significant population of cells (30%) was noted to be HLA-DR positive, and negative for macrophage and lymphocyte markers. Some of these cells had a dendritic morphology. The coexpression of HLA-DQ and HLA-DR may play an important role in antigen presentation and disease chronicity in RA.
 ...
PMID:Increased expression of HLA-DQ antigens by interstitial cells and endothelium in the synovial membrane of rheumatoid arthritis patients compared with reactive arthritis patients. 276 9

The predominant genetic elements contributing to HLA-associated disease susceptibility have been localized within the HLA-D, or class II, region of the major histocompatibility complex for a large number of autoimmune diseases. Two likely candidate susceptibility genes in this region have been identified: the DQ beta 3.2 gene is the single allele most highly associated with type I diabetes (IDDM) and accounts for the HLA-DR4 association with that disease. DNA sequence analysis and mutagenesis studies implicate a small set of key residues within the DQ3.2 molecule as critical polymorphic residues likely contributing to disease-associated immune mechanisms. Different class II genes, Dw4 and Dw14, specific alleles at the DR beta locus, account for the HLA-DR4 association with rheumatoid arthritis (RA). A single cluster of polymorphic residues within the DR beta molecule may be sufficient to account for nearly all of the structural and genetic contributions of the HLA complex to the pathogenesis of RA.
 ...
PMID:Determinants of genetic susceptibility in HLA-associated autoimmune disease. 279 47

IgG antibodies reactive with human umbilical vein endothelial cells were found in 19 out of 28 patients with rheumatoid vasculitis (RV), in four out of 24 patients with rheumatoid arthritis (RA), in seven out of 10 patients with systemic lupus erythematosus (SLE), but not in healthy donors. In four patients with RV who were followed longitudinally, regression of vasculitic episodes coincided with decreasing titres of anti-endothelial antibodies (AEA). Binding activity to endothelial cells was observed in intact IgG and F(ab')2 fragments of IgG. AEA activity was unrelated to antibodies against nuclear, blood group or major histocompatibility complex antigens and did not involve immune complexes. AEA activity was not specific for endothelial cells since the AEA-positive sera and the IgG fractions prepared from these sera also reacted with fibroblasts. Adsorption of positive sera and corresponding IgG fractions with endothelial cells decreased the IgG binding reactivity on both fibroblasts and endothelial cells. These findings show that RV patients have IgG-AEA, and suggest that these antibodies may play a role in the pathogenesis of the disease.
 ...
PMID:Anti-endothelial cell antibodies in patients with rheumatoid arthritis complicated by vasculitis. 280 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>