Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese populations

ObjectiveRheumatoid arthritis (RA) is a chronic autoimmune disease characterized with joint destructions; environmental and genetic factors were thought to be involved in the etiology of RA. The production of anti-citrullinated peptide antibodies (ACPA) is specifically associated with RA. DRB1 is associated with the susceptibility of RA, especially ACPA-positive RA [ACPA(+)RA]. However, a few studies reported on the independent associations of DPB1 alleles with RA susceptibility. Thus, we investigated the independent association of DPB1 alleles with RA in Japanese populations.MethodsAssociation analyses of DPB1 were conducted by logistic regression analysis in 1667 RA patients and 413 controls.ResultsIn unconditioned analysis, DPB1*04:02 was nominally associated with the susceptibility of ACPA(+)RA (P = 0.0021, corrected P (Pc) = 0.0275, odds ratio [OR] 1.52, 95% confidence interval [CI] 1.16–1.99). A significant association of DPB1*02:01 with the susceptibility of ACPA(+)RA was observed, when conditioned on DRB1 (Padjusted = 0.0003, Pcadjusted = 0.0040, ORadjusted 1.47, 95%CI 1.19–1.81). DPB1*05:01 was tended to be associated with the protection against ACPA(+)RA, when conditioned on DRB1 (Padjusted = 0.0091, Pcadjusted = 0.1184, ORadjusted 0.78, 95%CI 0.65–0.94). When conditioned on DRB1, the association of DPB1*04:02 with ACPA(+)RA was disappeared. No association of DPB1 alleles with ACPA-negative RA was detected.ConclusionThe independent association of DPB1*02:01 with Japanese ACPA(+)RA was identified

Association of Human Leukocyte Antigen with Interstitial Lung Disease in Rheumatoid Arthritis: A Protective Role for Shared Epitope

INTRODUCTION: Interstitial Lung Disease (ILD) is frequently associated with Rheumatoid Arthritis (RA) as one of extra-articular manifestations. Many studies for Human Leukocyte Antigen (HLA) allelic association with RA have been reported, but few have been validated in an RA subpopulation with ILD. In this study, we investigated the association of HLA class II alleles with ILD in RA. METHODS: An association study was conducted on HLA-DRB1, DQB1, and DPB1 in 450 Japanese RA patients that were or were not diagnosed with ILD, based on the findings of computed tomography images of the chest. RESULTS: Unexpectedly, HLA-DRB1*04 (corrected P [Pc] = 0.0054, odds ratio [OR] 0.57), shared epitope (SE) (P = 0.0055, OR 0.66) and DQB1*04 (Pc = 0.0036, OR 0.57) were associated with significantly decreased risk of ILD. In contrast, DRB1*16 (Pc = 0.0372, OR 15.21), DR2 serological group (DRB1*15 and *16 alleles) (P = 0.0020, OR 1.75) and DQB1*06 (Pc = 0.0333, OR 1.57, respectively) were significantly associated with risk of ILD. CONCLUSION: HLA-DRB1 SE was associated with reduced, while DR2 serological group (DRB1*15 and *16) with increased, risk for ILD in Japanese patients with RA

Characterization of interface state density of three-dimensional Si nanostructure by charge pumping measurement

Adopting the gated p-i-n diode configuration, the interface state density (Dit) at the Si/SiO2 interface of Si fin structures on Silicon-on-Insulator (SOI) wafers has been systematically studied using charge pumping method. The optimal forming gas annealing temperature for the three-dimensional (3D) surface is extracted. A new methodology for separately quantifying the local Dit at different regions of the 3D surfaces (i.e., the top/side walls and the corners) is also derived by characterizing the fins with various widths and the planar counterparts. The results validate the necessity to independently consider the corner regions, at which substantially high local Dit situates, and thus further clarify the origin of high Dit at 3D surfaces. © 2013 Elsevier Ltd. All rights reserved

Association of increased frequencies of HLA-DPB1*05:01 with the presence of anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese rheumatoid arthritis and systemic lupus erythematosus patients.

INTRODUCTION: Autoantibodies to ribonucleoprotein are associated with a variety of autoimmune diseases, including rheumatoid arthritis (RA). Many studies on associations between human leukocyte antigen (HLA) alleles and RA have been reported, but few have been validated in RA subpopulations with anti-La/SS-B or anti-Ro/SS-A antibodies. Here, we investigated associations of HLA class II alleles with the presence of anti-Ro/SS-A or anti-La/SS-B antibodies in RA. METHODS: An association study was conducted for HLA-DRB1, DQB1, and DPB1 in Japanese RA and systemic lupus erythematosus (SLE) patients that were positive or negative for anti-Ro/SS-A and/or anti-La/SS-B antibodies. RESULTS: An increased prevalence of certain class II alleles was associated with the presence of anti-Ro/SS-A antibodies as follows: DRB1*08:03 (Pc = 3.79×10(-5), odds ratio [OR] 3.06, 95% confidence interval [CI] 1.98-4.73), DQB1*06:01 (Pc = 0.0106, OR 1.70, 95%CI 1.26-2.31), and DPB1*05:01 (Pc = 0.0040, OR 1.55, 95%CI 1.23-1.96). On the other hand, DRB1*15:01 (Pc = 0.0470, OR 3.14, 95%CI 1.63-6.05), DQB1*06:02 (Pc = 0.0252, OR 3.14, 95%CI 1.63-6.05), and DPB1*05:01 (Pc = 0.0069, OR 2.27, 95% CI 1.44-3.57) were associated with anti-La/SS-B antibodies. The DPB1*05:01 allele was associated with anti-Ro/SS-A (Pc = 0.0408, OR 1.69, 95% CI 1.19-2.41) and anti-La/SS-B antibodies (Pc = 2.48×10(-5), OR 3.31, 95%CI 2.02-5.43) in SLE patients. CONCLUSION: HLA-DPB1*05:01 was the only allele associated with the presence of both anti-Ro/SS-A and anti-La/SS-B antibodies in Japanese RA and SLE patients

Protective Effect of the <i>HLA-DRB1*13:02</i> Allele in Japanese Rheumatoid Arthritis Patients

<div><p>Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. Certain <i>HLA-DRB1</i> “shared-epitope” alleles are reported to be positively associated with increased RA susceptibility, whereas some of the other alleles may be negatively associated. However, studies on the latter are rare. Here, we focus on the protective effects of <i>DRB1</i> alleles in Japanese RA patients in an association study. Relative predispositional effects (RPE) were analyzed by sequential elimination of carriers of each allele with the strongest association. The protective effects of <i>DRB1</i> alleles were investigated in patients stratified according to whether they possessed anti-citrullinated peptide antibodies (ACPA). The <i>DRB1*13:02</i> allele was found to be negatively associated with RA (<i>P</i> = 4.59×10⁻¹⁰, corrected <i>P</i> (<i>P</i>c) = 1.42×10⁻⁸, odds ratio [OR] 0.42, 95% CI 0.32–0.55, <i>P</i> [RPE] = 1.27×10⁻⁶); the genotypes <i>DRB1*04:05</i>/<i>*13:02</i> and <i>*09:01/*13:02</i> were also negatively associated with RA. The protective effect of <i>*13:02</i> was also present in ACPA-positive patients (<i>P</i> = 3.95×10⁻⁸, <i>P</i>c = 1.22×10⁻⁶, OR 0.42, 95%CI 0.31–0.58) whereas <i>*15:02</i> was negatively associated only with ACPA-negative RA (<i>P</i> = 8.87×10⁻⁵, <i>P</i>c = 0.0026, OR 0.26, 95%CI 0.12–0.56). Thus, this study identified a negative association of <i>DRB1*13:02</i> with Japanese RA; our findings support the protective role of <i>DRB1*13:02</i> in the pathogenesis of ACPA-positive RA.</p></div