Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis.

OBJECTIVE: To examine the relationship of the HLA-DRB1 shared epitope (SE) to rheumatoid vasculitis, using individual patient data (IPD) meta-analytic methods. METHODS: Published studies that enrolled adult patients with rheumatoid arthritis (RA) were identified by searches of Medline and Embase, and by manual searches of medical journals. All authors were contacted for IPD. Meta-analyses were performed to assess the association of SE presence, dose, and genotype with rheumatoid vasculitis. RESULTS: A total of 14 studies and 1,568 patients (129 with vasculitis) were included in the analysis. RA patients with vasculitis were significantly more likely to have rheumatoid nodules (odds ratio [OR] 2.5, 95% confidence interval [95% CI] 1.5-3.9], but there was no significant association with male sex, rheumatoid factor positivity, or erosive disease. No significant association was observed between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid vasculitis (summary OR 1.4, 95% CI 0.7-2.7). Analysis by SE genotype, however, demonstrated a striking relationship of vasculitis to 3 genotypes containing a double dose of the SE, specifically HLA-DRB1*0401/*0401 (OR 6.2, 95% CI 1.01-37.9), *0401/*0404 (OR 4.1, 95% CI 1.1-16.2), and *0101/*0401 (OR 4.0, 95% CI 1.4-11.6). CONCLUSION: The HLA-DRB1 SE genotypes *0401/*0401, *0401/*0404, and *0101/*0401 may be of particular importance to rheumatoid vasculitis. It is hoped that additional investigation of these and other SE genotypes will lead to improved insight into the mechanisms influencing the clinical expression of RA.

T2 relaxation time measurements in osteoarthritis.

Quantification of changes in T(2) relaxation time, in human cartilage, with progression of osteoarthritis (OA), and evaluation of qualitative correlations with clinical evaluation, histology and polarized light microscopy (PLM). Cartilage-bone plugs were harvested from fresh cadaveric knees (n = 10) and specimens after surgical knee replacement (n = 2) at 12 locations, including lateral and medial sides of tibia, femora and patella. Magnetic resonance imaging was performed at 1.5 Tesla using a.2D spin echo sequence. Histological slices were assessed for OA severity through a grading scale based on combined histological and PLM results. T(2) values in clinically moderate OA were generally higher than in severe OA and normal cartilage. Significant association was established between normal and early OA subjects and T(2) variation, in the medial compartment of the knee (p < 0.05) but especially in the medial tibial cartilage (p < 0.00005). As expected, medial and lateral tibio-femoral compartments underwent more severe degeneration. Additionally, there were intracompartmental variation of the relaxation times and histological patterns, which demonstrate the underlying focal involvement of OA in the knee. Furthermore, T(2) values reflected OA pathogenesis with a positive correlation with histology grading scale. Finally, increased T(2) is correlated to histological degeneration of cartilage and may be a good marker for early OA in tibial articular cartilage.

Lack of association of the HLA-DRB1 shared epitope with rheumatoid nodules: an individual patient data meta-analysis of 3,272 Caucasian patients with rheumatoid arthritis.

OBJECTIVE: The objective of this individual patient data (IPD) meta-analysis was to examine the relationship of rheumatoid nodules to the HLA-DRB1 shared epitope (SE) and to individual SE genotypes. METHODS: English-language studies that enrolled adult non-Hispanic Caucasian patients with rheumatoid arthritis (RA) were identified by searches of Medline and Embase, and by manual searches of medical journals. All authors were contacted for IPD. Meta-analysis was performed to assess the association of SE presence, dose, and genotype with rheumatoid nodules. Meta-analyses adjusted for disease duration and cumulative meta-analyses were also performed to assess the influence of RA duration and year of study publication on the results. RESULTS: A total of 24 studies and 3,272 patients were available for analysis. IPD were obtained for 22 of the studies. There was a nonsignificant association between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence interval [95% CI] 0.97-1.6). Analysis by SE genotype, however, demonstrated a weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95% CI 1.1-1.8). No other genotypes achieved statistical significance in the adjusted or unadjusted analyses. CONCLUSION: The presence of the HLA-DRB1 SE does not appear to significantly increase the risk of rheumatoid nodules among Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative, suggesting only a potential (and at most modest) role of the DRB1*0401 SE allele. Results from this IPD meta-analysis implicate other genetic, stochastic, and/or environmental factors in the susceptibility to rheumatoid nodules.