ABSTRACT
OBJECTIVES: Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. METHODS: A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene. RESULTS: A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found. CONCLUSIONS: MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.
Subject(s)
Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease , Histocompatibility Antigens Class I/genetics , Adaptor Proteins, Signal Transducing , Adolescent , Adult , Aged , Aged, 80 and over , Female , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Histocompatibility Antigens Class II/genetics , Histocompatibility Testing/methods , Humans , Linkage Disequilibrium , Male , Middle AgedABSTRACT
The complement receptor type 1 (CR1) levels on erythrocyte membranes from 23 patients with PsA was determined by using ELISA. Six patients had an axial form, the rest had peripheral arthritis (10 polyarthritis and seven oligoarthritis). A significant decrease in levels of this receptor was found in patients with polyarthritis compared with healthy controls. Non-significant differences were found when comparing the other two groups of patients with the controls, although the mean values of CR1 were lower in the patients' group. We also found an inverse correlation between CR1 levels and articular index, but not with ESR, CRP or disease duration. No differences in the CR1 density were obtained for HLA-B27 positive and HLA-B27 negative patients.
Subject(s)
Arthritis, Rheumatoid/blood , Erythrocytes/chemistry , Receptors, Complement/analysis , Adult , Aged , Arthritis, Rheumatoid/immunology , Enzyme-Linked Immunosorbent Assay , Erythrocytes/pathology , Erythrocytes/ultrastructure , Female , HLA-B27 Antigen/analysis , Humans , Male , Middle AgedABSTRACT
We carried out a prospective study of the clinical, laboratory and radiological features of 180 patients with psoriatic arthritis. We initially classified our patients into five groups as described in the publications of Moll and Wright. Thirty-seven per cent had oligoarthritis, 36% polyarthritis, 23% spondarthritis (sacroiliitis and/or spondylitis) and 4% had the mutilans form. The distal joint arthritis type did not exist as an entity and the distal interphalangeal (DIP) joints were affected in all groups. The spondarthritis form includes patients with exclusively axial manifestations and also those who in addition have peripheral arthritis (oligoarthritis, polyarthritis, DIP arthritis). Only 53% of our patients had nail involvement. We found an increase of IgA levels in patients with axial disease. This suggests a relationship between ankylosing spondylitis and psoriatic spondylitis. The HLA-B17/Cw6 association increased in the oligoarticular form. The increase of antigen B17 correlated with the spondarthritic and oligoarthritis forms whereas Cw6 was more important in the oligoarthritis form. An increase of the HLA-B27/Cw1 association and the spondarthritic form was also found. Moreover, we detected a greater incidence of the HLA-B27 antigen in patients with bilateral sacroiliitis (85%) than in patients with unilateral sacroiliitis (22%). Our work revealed that PA is not a harmless disease; 57% of our patients had erosive arthritis while 19% had ARA class III or IV functional impairment.
