Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


HLA-DRB501:05 Is a Risk Factor for Systemic Sclerosis with Interstitial Lung Disease.

Odani,  Toshio, Yasuda,  Shinsuke, Kubota,  Ayaka, Nakagawa,  Hisako, Fujieda,  Yuichiro, Otomo,  Kotaro, Kato,  Masaru

Background/Purpose:

Interstitial lung disease (ILD) is a serious complication of Systemic Sclerosis (SSc). Recently, a variety of markers including cytokines, disease-specific autoantibodies and genetic backgrounds have been reported to be associated with SSc. However, few studies have focused on association between specific markers and SSc-related ILD. We aimed to elucidate markers associated with ILD in patients with SSc.

Methods:

This study was approved by the ethical committee of Hokkaido University Graduate School of Medicine. RNA was prepared from peripheral blood mononuclear cells (PBMCs) from 14 SSc patients. Fourteen samples were divided into 4 sets of RNA pools according to the presence or the absence of ILD, and to the treatment (conventional or hematopoietic stem cell transplantation), then were subjected to DNA microarray. The expression levels of HLA-DRB5 in each individual were evaluated by real-time qPCR for 43 SSc patients (25 with ILD, 18 without ILD), 42 patients with other autoimmune diseases and 10 healthy controls. Genomic DNA samples were collected from147 healthy controls and 70 SSc patients who received high-resolution CT scan for the evaluation of ILD. HLA-DRB5 genotype was analyzed by sequence specific primers method.

Results:

Microarray analysis revealed that HLA-DRB5 was the only gene commonly up-regulated in patients with ILD compared to those without in both treatment groups. HLA-DRB5 gene expression was significantly higher in PBMCs from SSc with ILD patients, than in those without ILD (P= 0.007). Although the frequencies of HLA-DRB5 carriers were not significantly frequent in all SSc patients compared to controls, HLA-DRB5 carriers were significantly more frequent in SSc patients with ILD (52.4 %) compared to those without ILD (25.0 %P= 0.022). Detailed genotyping of HLA-DRB5 gene revealed that HLA-DRB5*01:05 allele was significantly more frequent in SSc patients (22.9 %; P <0.001), Especially DRB5*01:05 allele was significantly more frequent in SSc patients with ILD (31.7 %, P < 0.001), compared to controls (5.4 %). (Table 1)

Table 1. Frequencies (%) of HLA-DRB5 alleles in patients with SSc with ILD, without ILD and in healthy controls

  SSc total N=70ILD(+) N=41ILD(-) N=29Controls N=147SSc vs controlsILD(+) vs controlsILD(-) vs controls
HLA-DRB5alleles(%)OR (95% CI)
DRB5*01*01:0112.99.817.214.30.89 (0.38–2.05)0.65 (0.21–2.01)1.25 (0.43–3.64)
 *01:0218.622.010.314.91.30 (0.61–2.75)1.83 (0.79–4.27)0.66 (0.18–2.35)
 *01:0522.931.710.35.45.15 (2.08–12.73)8.07 (3.06–21.28)2.00 (0.50–8.06)
DRB5*02*02:024.294.882.02.15 (0.42–10.93)2.46 (0.40–15.25) 
Numbers (%) Chi-square test or Fisher's exact test

Conclusion:

HLA-DRB5*01:05 allele is a risk factor for the development of ILD in patients with SSc.

To cite this abstract, please use the following information:
Odani, Toshio, Yasuda, Shinsuke, Kubota, Ayaka, Nakagawa, Hisako, Fujieda, Yuichiro, Otomo, Kotaro, et al; HLA-DRB501:05 Is a Risk Factor for Systemic Sclerosis with Interstitial Lung Disease. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2310
DOI:

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