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)

To further investigate a clinical impression that patients with early onset pauciarticular juvenile rheumatoid arthritis (EOPA-JRA) who carry HLA-DQw1 have more severe arthritis, we subtyped HLA-DQw1 in American midwestern patients with EOPA-JRA. The HLA-DQA1*0101 subtype was present in 10 of 19 patients who developed persistent polyarticular erosive disease compared with 18 of 92 healthy controls (chi 2 = 9.13, p = 0.003, RR = 4.6), and occurred more frequently in this polyarticular group than in patients without polyarticular erosive disease (chi 2 = 4.11, p = 0.040, RR = 3.0). The presence of HLA-DQA1*0101 was significantly lower in patients with chronic iridocyclitis than in patients without chronic iridocyclitis (chi 2 = 7.07, p = 0.008, RR = 0.21). In HLA-DQA1*0101 positive patients, DNA sequences of the beta-1 domain of the HLA-DQ alpha and HLA-DQ beta genes (HLA-DQA1*0101, HLA-DQB1*0501 and HLA-DQB1*0503) were identical to those in controls. In this midwestern EOPA-JRA population, HLA-DQA1*0101 or genes in linkage disequilibrium with it, are associated with a cohort of patients with EOPA-JRA with distinct clinical characteristics.
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PMID:HLA-DQA1*0101 haplotypes and disease outcome in early onset pauciarticular juvenile rheumatoid arthritis. 168 Jan 92

Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA1*0501) and DQA1.8 (DQA1*0401, *0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA.
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PMID:A model for the role of HLA-DQ molecules in the pathogenesis of juvenile chronic arthritis. 168 21

We studied the first domain of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci of 67 HLA-DRw8-positive Caucasians including 43 with early-onset pauciarticular juvenile rheumatoid arthritis (EOPA-JRA, alternatively known as early-onset pauciarticular juvenile chronic arthritis). Serology, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) oligotyping revealed that 62, including all the EOPA-JRA patients, carried the HLA-DRB1*0801, DQA1*0401, DQB1*0402 genotype. Approximately one-fifth of the controls carried atypical HLA-DRB1, HLA-DQA1, and/or HLA-DQB1 loci on their HLA-DRw8 haplotype confirmed by family studies. DNA sequences of HLA-DRB1, DQA1, and DQB1 alleles in patients and controls were identical to those previously reported. Disease association studies in 113 EOPA-JRA patients and 207 controls unselected for HLA-DRw8 revealed that the HLA-DRB1*0801, DQA1*0401, DQB1*0402 genotype was associated with a higher relative risk (RR) for disease (RR = 12.8, chi 2 = 48.8, P less than 10(-4)) than was the serologically defined presence of HLA-DRw8 (RR = 8, chi 2 = 39, P less than 10(-4)). Further analysis suggested that the DQ genes on HLA-DRw8 haplotypes are as likely as the DR genes to contribute to the pathogenesis of EOPA-JRA. This study increases to five the number of HLA-DR/DQ haplotypes identified in HLA-DRw8 Caucasians.
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PMID:A distinct HLA-DRw8 haplotype characterizes patients with juvenile rheumatoid arthritis. 197 63

DNA profiles (immunoprints) were generated for 120 patients suffering from early onset pauciarticular chronic arthritis (EOPA-JCA) and > 500 healthy controls utilizing highly polymorphic microsatellites in the vicinity of immunorelevant genes. Six T cell receptor (TCR) markers for the CD3D, TCRDVAJ, TEA, TCRBV6S1, BV6S3, BV6S7 and BV13S2 genes were analysed. Furthermore markers for the cell surface molecule CD40L, for cytokine genes (IL-1A, IL-2, IFN-alpha, FGF-alpha, TNF-alpha), the chromosomal region of the IRF2 and the cytokine receptor gene IL5RA were studied as well as two polymorphisms within the promotor region of the TNF-alpha gene. Coding region polymorphisms were evidenced indirectly by repeat length variation or they were predicted from the microsatellite distribution profiles and then confirmed by direct sequence analysis. Statistical evaluations were performed with respect to known predispositions, predominance of females (> 80%) and HLA-DR and -DQ haplotypes. Cell surface molecules (TCR, CD40L, IL5RA) as well as almost all cytokines (IL-1A, IFN alpha, FGFA, IRF2 region) were excluded as predisposing in our JCA panel. The TNF-alpha microsatellite alleles (GT)10-12 contribute considerably to manifestation of the disease, in HLA-DRB1*11(12) individuals (RR = 12.8). The TNF-alpha allele is not found in linkage disequilibrium with HLA-DRB1*11(12) and may be present on either chromosome 6. Thus, a novel susceptibility factor probably within the TNFA/TNFB gene region has been identified via linkage with the TNF-alpha microsatellite allele. Apparently complex compositions of the genetic background rather than single genes provide the precondition for manifestation of the autoimmune disease EOPA-JCA. Immunoprinting unravels the variability of the immunological genome via the semi-directed microsatellite approach efficiently.
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PMID:Immunoprinting excludes many potential susceptibility genes as predisposing to early onset pauciarticular juvenile chronic arthritis except HLA class II and TNF. 749 83

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 set of 200 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) from Munich (165) and Prague (35) was investigated for the subtypes of HLA-DRB1*03, *08, *11, *12, *13 and *14. In addition, the relationship of DRB1, DQA1, DQB1 and DPB1 alleles with iridocyclitis in patients with EOPA-JCA was investigated. Subtyping for DRB1*03 was not informative, as all DR3 positive patients and all except one of the controls possessed DRB1*0301. Thus, the role of DRB1*0302 could not be assessed. The subtypes for DRB1*12, *13, and *14 did not reveal any statistically significant difference between patients and controls. In contrast, the subtype DRB1*1104 was the one most strongly associated with EOPA-JCA (chi 2 31.2, p value < 10(-6)). It appears that the subtype DRB1*1103 may also be associated with EOPA-JCA. The association of EOPA-JCA with DR8 is almost exclusively due to the subtype *0801. For the other alleles *0802, *0803, and *0804 there is no evidence for or against involvement in JCA. The analysis of iridocyclitis in EOPA-JCA revealed that DRB1*1104 is not more frequent in patients with eye disease than in patients without eye disease. The presence of DRB1*01 appears to convey some protective effect against the occurrence of iridiocylitis in EOPA-JCA, as had been previously observed by Melin-Aldana et al.
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PMID:Subtypes of HLA-DRB1*03, *08, *11, *12, *13 and *14 in early onset pauciarticular juvenile chronic arthritis (EOPA) with and without iridocyclitis. 795 32

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

We investigated the polymorphic second exon of the HLA-DPB1 and HLA-DRB1 genes, using in vitro DNA amplification by polymerase chain reaction (PCR) and oligonucleotide hybridization in 136 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) and 199 healthy controls. The analysis of the HLA-DRB1 system revealed that most of the DRB1 alleles are not indifferent with respect to susceptibility to EOPA-JCA. There is a hierarchy of susceptible (DRB1*08, DR5), "permissive" (DRB1*01), moderately "protective" (DR2, DRB1*04), and "protective" (DRB1*07) alleles. In contrast, no hierarchy could be shown for the HLA-DPB1 system. DPB1*0201 was found to be susceptible. The relatively frequent alleles DPB1*0402 and DPB1*0401 seem to be indifferent. The associations with DPB1*0201, DR5, and DRB1*08 are independent of each other: that is to say they, are not brought about by linkage disequilibrium. The susceptible alleles DPB1*0201 and DR5 show evidence for interaction in the pathogenesis of EOPA-JCA. Interaction seems likely between DPB1*0201 and DRB1*08, DR5 and DRB1*08, or between DR6 and DRB1*08. The strongest interaction exists between DPB1*0201 and a common DQ factor associated with both DR5 and DRB1*08. Finally, we observed a hierarchy among the various marker combinations, where the risk of developing EOPA-JCA increases with the number of associated markers present in an individual.
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PMID:HLA-DP/DR interaction in early onset pauciarticular juvenile chronic arthritis. 843 19

To determine whether patients with rheumatoid factor (RF)-negative, antinuclear antibody (ANA)-positive oligo/polyarthritis are clinically and immunogenetically distinct from RF-positive rheumatoid arthritis (RA) and whether this subset of patients is the adult counterpart of early-onset pauciarticular juvenile chronic arthritis (EOPA JCA), we retrospectively studied 20 adult patients with RF-negative, ANA-positive arthritis. After a median duration of 3.25 years, only half of our patients had active synovitis. Seventy-five per cent were completely or reasonably self-sufficient according to the HAQ index. In contrast to the results in a group of 30 RF-positive RA patients, the percentage of patients having at least one of the susceptibility alleles (HLA DR1 or HLA-DR4) was not significantly higher in patients with RF-negative, ANA-positive arthritis than in controls. Furthermore, none of our RF-negative, ANA-positive patients had two susceptibility alleles, whereas 16.5% of RF-positive RA patients had both DR1 and DR4 or DR4 homozygosity. In conclusion, our results show that patients with RF-negative, ANA-positive oligo/polyarthritis are immunogenetically distinct from RF-positive RA and tend to have a better articular prognosis. The absence of typical ocular features and of the characteristic HLA-DR markers suggests that these patients cannot be considered as the adult counterpart of EOPA JCA.
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PMID:Adult seronegative arthritis with antinuclear antibodies: a distinct group of patients with a different immunogenetic pattern from seropositive rheumatoid arthritis and a good outcome. 878 76

The expression of m-fas/apo1 (CD95) and its soluble form (s-fas) was studied in patients with early onset pauciarticular (n = 23) and systemic juvenile chronic arthritis (n = 7). RNA was prepared from peripheral blood of patients and 22 healthy controls and from 23 samples derived from the synovial fluid of JCA patients. The ratio of m-fas/s-fas transcripts was calculated by densitometry of fas-specific RT-PCR products. An inverted ratio of m-fas/s-fas transcripts was found in PBMC and mononuclear cells from the joints of early onset pauciarticular JCA patients. The m-fas/s-fas ratios were similar in PBMC and mononuclear cells from synovial fluid. PBMC from patients with a systemic JCA showed the same m-fas/s-fas ratio as healthy controls, with an inverted ratio of both transcripts in cells from the synovial fluid. The data indicate a role of Fas/Apo1 regulated apoptosis in EOPA-JCA which is not limited to the affected joints.
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PMID:Inverted ratio of m-fas/s-fas expression in early onset pauciarticular juvenile chronic arthritis. 1055 97


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