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)

One hundred and twelve well-studied patients with a prior diagnosis of juvenile rheumatoid arthritis were differentiated into seven clinically distinct subgroups, including a group in whom recognizable ankylosing spondylitis had developed by time of follow-up. An apparent increased prevalence of HLA-B27 in the entire series (26%) was clearly related to its increased prevalence in only two subgroups: patients whose disease had progressed to overt ankylosing spondylitis (five of five patients) and boys with pauciarticular arthritis whose disease would be consistent with early ankylosing spondylitis (11 of 18 patients). There were no significant associations of B27 with systemic onset JRA, polyarticular JRA, pauciarticular JRA in girls, or JRA with chronic iridocyclitis. The only other significant alterations found were increased prevalences of HLA-A2 and HLA-BW15 in patients with polyarticular disease without identifiable rheumatoid factor. This study emphasizes that the clinical disorders included under the category of juvenile rheumatoid arthritis represent more than a single disease and that this heterogeneity must be considered in interpreting studies such as those of histocompatibility typing.
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PMID:Histocompatibility antigens in childhood-onset arthritis. 127 Nov 90

We report the results of research on human leukocyte allo-antigen (HLA) and rheumatic fever (RF), the first published study to be carried out among Turkish children with RF. Ninety-three Turkish children, aged between 6 and 16 years (mean: 8 +/- 2.6), with RF participated in the study. Of the total, 26 patients had their first attack and 39 had acute rheumatic activity at the time of registration. The results demonstrate (1) negative but not significant association between HLA-A2 and RF; (2) a positive association between HLA-DR4 and RF (p less than 0.001); (3) a significant association between HLA-DR4 and carditis, but not with isolated arthritis. These results corroborate the concept of race-specific genetically determined familial susceptibility to the development of rheumatic heart disease.
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PMID:HLA and rheumatic fever in Turkish Children. 151 38

The mechanism by which HLA-B27 confers genetic susceptibility to the seronegative spondyloarthropathies ankylosing spondylitis, Reiter's syndrome, and reactive arthritis, is not well understood. The current concept of an extraarticular bacterial infection functioning as the triggering event in a genetically susceptible host suggests the possibility of direct microbial-MHC interaction. We have addressed the role of HLA-B27 in microbial-host cell interaction by examining invasion by putatively arthritogenic gram-negative bacteria. Target cells used were murine L cells transfected with HLA-B27, HLA-A3, HLA-A2, HLA B44, HLA B18, or pSV2neo vector alone. Relative to the pSV2neo control and the HLA-A3 transfectant, HLA-B27-transfected cells demonstrated a consistent decrease in invasion for each of the following pathogens: Salmonella typhimurium (45 +/- 2% decrease), Shigella sonnei (53 +/- 13% decrease), Shigella flexneri (45 +/- 5% decrease), and enteroinvasive Escherichia coli (57 +/- 8% decrease). This decrease was specific for the HLA B27-transfected L cells and was not observed in the other B allele transfectants. The decreased invasion in the HLA-B27 transfectants is not the result of either altered endogenous mouse class I expression as a result of human class I transfection or increased intracellular bacterial killing within the B27 transfectants. There was an inverse relationship between the amount of surface expression of HLA-B27, as measured by FACS, and the degree of invasion. Blocking of surface B27 Ag with anti-B27 mAb augmented bacterial invasion in the B27 transfectants. These studies demonstrate a novel bacterial-B27 interaction that may have relevance to the pathogenesis of B27-related arthritis.
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PMID:HLA-B27 expression modulates gram-negative bacterial invasion into transfected L cells. 158 45

Fifty two patients with juvenile chronic arthritis (JCA) and 22 patients with arthritis of short duration (transient arthritis, TA) were studied in a follow up investigation. Nineteen (37%) of the patients with JCA had peripheral arthritis or sequelae in the form of contractures at follow up, and in addition one patient was treated with corticosteroids. In contrast, only one (5%) of the 22 patients with TA had peripheral arthritis at follow up. Back pain or limitation, or both, was registered in many of the men. Sacroiliitis, verified by x ray, was often found both in JCA (39/46, 85%) and in TA (16/21, 76%). For JCA an association was confirmed with HLA-A2 and HLA-DRw8 and a negative association with HLA-DR4, and in pauciarticular JCA, in addition, a decrease of DR7. A new finding was a low prevalence of HLA-B27 in women with JCA and grade 3 or 4 sacroiliitis (2/14, 14%).
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PMID:Clinical, HLA, and roentgenological follow up study of patients with juvenile arthritis: comparison between the long term outcome of transient and persistent arthritis in children. 253 95

To investigate the genetics of susceptibility to early onset pauciarticular juvenile chronic arthritis (JCA), 158 unrelated ethnic British patients with a mean disease onset of 3.2 years, together with controls, were tested for HLA-A, B, C, and DR antigens. Additionally, 117 patients were also investigated for complement Bf and C4 markers. New observations included an increased frequency of the C4B 2 allotype (p corrected (pc) less than 0.02) and C4A 4,B 2 phenotype (p less than 0.0005). Findings suggested a unique increase of the haplotype HLA-DRw8, Bf*S, C4A*4, C4B*2, HLA-B39, possibly predisposing to more severe disease. Strong positive associations were confirmed with HLA antigens A2 (pc = 2.5 X 10(-8)), DRw8 (pc = 3.5 X 10(-14)), DR5 (pc less than 0.02), DRw52 (pc = 2.8 X 10(-6)) and DR5, w8 phenotype (pc = 3.9 X 10(-6)), and negative associations with DR7 (pc = 5.8 X 10(-7)), DR4 (pc less than 0.002), and DRw53 (pc = 0.004). Antinuclear antibody (ANA) seropositivity correlated with DR5 (p less than 0.02), and in children with chronic iridocyclitis (CIR) Bw62 incidence was raised (p less than 0.03) and B44 reduced (p less than 0.03). HLA-A2 was found in 88% of ANA+, CIR+ patients (p less than 0.01). A significant excess of DR5, w8 heterozygotes was present (relative risk = 41.1) and a lack of corresponding homozygotes. Results are inconsistent with a recessive, dominant, or intermediate mode of inheritance of susceptibility, and favour the existence of at least two DR linked 'disease' genes. Moreover, there may be an interaction in heterozygotes of combinatorial factors associated with DR5 and DRw8 in enhancing susceptibility. Possible immunogenetic mechanisms underlying the observed associations with three antigen classes are discussed. Evidence here suggests a role for the HLA-DQ locus in determining susceptibility to this disease.
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PMID:Genetic susceptibility to early onset pauciarticular juvenile chronic arthritis: a study of HLA and complement markers in 158 British patients. 348 35

The responses of synovial lymphocytes to Chlamydia/Ureaplasma and to enteric antigens were studied in 31 patients with arthritis confined to knee joints, 15 patients with sexually-transmitted Reiter's syndrome, 9 with enteric Reiter's syndrome, and 24 with rheumatoid arthritis. The frequency of HLA antigens was studied in 28 patients with knee joint arthritis; this group was characterized by elevated frequencies of HLA-A2 and DR1. A subgroup of 8 responders to Chlamydia/Ureaplasma was characterized by an increase of HLA-Bw44 and DR7 or 8, while a subgroup of 8 responders to enteric antigens was characterized by increases of HLA-A1 and DR5. The frequency of HLA-B27 in the groups responding to antigens was 25-30%, less than half the frequency in patients with Reiter's syndrome.
Arthritis Rheum 1984 Oct
PMID:Arthritis confined to knee joints. Synovial lymphocyte responses to microbial antigens correlate with distribution of HLA. 648 96

HLA typing studies were performed on a group of 16 patients with acute Brucella-induced reactive arthritis and results were compared to those obtained in 16 patients with acute brucellosis but without arthritis and to 55 normal control subjects. No increased prevalence of any HLA antigen was noted between patients and control groups. HLA-B27 frequency was diminished in the Peruvian population studied. The most interesting finding was the presence of a statistically significant low frequency of HLA-A2 in the disease group suggesting that this antigen may play a protective role for the development of brucellosis.
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PMID:Reactive arthritis associated with brucellosis: HLA studies. 729 64

Early-onset pauciarticular juvenile chronic arthritis (EOPA-JCA) has associations with different alleles of the MHC region (HLA-A2, DR5, 6, 8, DQA1*0401, *0501, *0601 and DPB1*0201). All susceptible DQA1 alleles carry an exclusive sequence motif. MHC-class II gene expression is controlled by 5' flanking upstream regulatory regions (URR). A hypervariable region in the promoter region of the HLA-DQA1 gene (-240 and -200 base pairs upstream) defines ten different QAP (DQA1-Promoter) alleles, which are associated with certain DQA1-alleles. The Y-Box in the DQA1 promoter (YC-Box -125 to -115 upstream from the ATG) differs from the consensus sequence (-123 A for G) of all other MHC class II Y-Boxes, resulting in a lower affinity to the NF-Y transcription factor and in a reduced expression of DQA1. A second substitution in the Y-Box of QAP 4.1 and 4.2 (-119 A for G) is found in the promoter alleles of the DQA1-alleles (DQA1*0401, *0501, *0601) and is strongly associated with susceptibility to EOPA-JCA.
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PMID:Early-onset pauciarticular juvenile chronic arthritis is associated with a mutation in the Y-box of the HLA-DQA1 promoter. 765 38

A total of 94 patients with juvenile chronic arthritis (JCA) was tested for HLA class I by serology and for class II by RFLP typing. Early onset JCA (EOPA) is associated with HLA-A2, DR5 and DR8 in both males and females. The combination (joint occurrence) of these JCA associated alleles (A2, DR5, DR8) is frequently seen in patients with chronic iridocyclitis. Late onset pauciarticular disease has an increased frequency of HLA-B27, especially in males. Our data confirm that polyarticular JCA with early childhood onset (< or = 4 years) is associated with DR5 and DR8 and has a different immunogenetic background from polyarticular JCA with later childhood (> 4 years) onset (associated with DR4).
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PMID:Class I associations and frequencies of class II HLA-DRB alleles by RFLP analysis in children with rheumatoid-factor-negative juvenile chronic arthritis. 810 7

To investigate the role of the class I MHC molecule HLA-B27 in the spondyloarthropathies, we produced rats transgenic for HLA-B27 and human beta 2-microglobulin. Of five lines bearing > 1 copy of each transgene and showing hemizygous expression of both transgenes, two (lines 21-4H and 33-3) developed spontaneous inflammatory disease that closely resembled B27-associated human disease. Two lines, 21-4L and 25-6, remained healthy even when homozygous for the transgene locus, whereas the 21-3 line, bearing the third highest transgene copy number, developed disease similar to that of the 21-4H and 33-3 lines only when homozygous for the transgene locus. The disease-prone lines showed higher expression of B27--thymic mRNA in utero, splenic mRNA by 5 days of age, and splenic cell surface protein by the time of disease onset--than the disease-resistant lines. Disease susceptibility thus appeared to correlate with gene copy number and the quantity of B27 in lymphoid cells. The increase in the amount of B27 protein did not appear to be simply a consequence of the inflammatory disease because 1) there was no similar change in endogenous RT1 class I expression; 2) no alteration of B27 expression occurred in 21-4H rats with adjuvant-induced arthritis; 3) in rats with inflammatory disease transgenic for HLA-A2 and the 21-4H transgene locus, A2 expression was the same as in healthy rats transgenic for A2 but not B27; and 4) the transgenes in disease-prone and disease-resistant lines were equally susceptible to induction by IFN-gamma. Immunocytochemistry of the distal colon, an early site of inflammation, showed that the B27 Ag is expressed at high levels in cells of the lamina propria, but not at all in colonic epithelial cells. Taken together, the data suggest that the B27 transgene is expressed in a copy number dependent, position-independent manner in lymphoid tissue and that disease results from the expression of B27 above a critical threshold level.
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PMID:Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression. 847 55


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