类风湿关节炎中人类白细胞抗原等位基因与慢性肺部疾病的关联

Association of human leukocyte antigen alleles with chronic lung diseases in rheumatoid arthritis.

作者信息

Oka Shomi, Furukawa Hiroshi, Shimada Kota, Sugii Shoji, Hashimoto Atsushi, Komiya Akiko, Fukui Naoshi, Suda Akiko, Tsunoda Shinichiro, Ito Satoshi, Katayama Masao, Nakamura Tadashi, Saisho Koichiro, Sano Hajime, Migita Kiyoshi, Nagaoka Shouhei, Tsuchiya Naoyuki, Tohma Shigeto

机构信息

Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara.

Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba

出版信息

Rheumatology (Oxford). 2016 Jul;55(7):1301-7. doi: 10.1093/rheumatology/kew025. Epub 2016 Apr 5.

DOI:10.1093/rheumatology/kew025

PMID:27048628

Abstract

OBJECTIVES

Chronic lung diseases including interstitial lung disease and airway disease (AD) occur in RA patients. Interstitial lung disease and AD in RA are extra-articular manifestations that influence the prognosis quoad vitam of RA. Studies on associations of HLA alleles with RA have been carried out, and shared epitopes of several alleles are reported to be associated with RA susceptibility. Few association studies in RA subpopulations with chronic lung diseases have been conducted. The aim of the study was to identify HLA alleles predisposing to RA phenotypes including the presence of AD.

METHODS

Associations of HLA-DRB1 and DQB1 alleles with chronic lung diseases in RA were analysed.

RESULTS

A positive association was found between the DR4 serological group and resistance to usual interstitial pneumonia [P = 0.0250, odds ratio (OR) 0.62, 95% CI: 0.41, 0.93]. The DR2 serological group was associated with susceptibility to usual interstitial pneumonia (P = 0.0036, OR = 1.86, 95% CI: 1.23, 2.81). An association was found for shared epitopes alleles with bronchiolitic AD (P = 0.0040, OR = 2.06, 95% CI: 1.24, 3.41). DQB103:01 was associated with bronchiectatic AD (P = 0.0021, corrected P-value (Pc) = 0.0315, OR = 1.99, 95% CI: 1.30, 3.06), as well as with emphysema (P = 0.0007, Pc = 0.0104, OR = 2.43, 95% CI: 1.49, 3.95). In combined analysis, a predisposing association of DQB103:01 (P = 1.94 ×10(-5), Pc = 0.0003, OR = 2.16, 95% CI: 1.53, 3.06) and a negative association of DQB1*03:02 (P = 0.0008, Pc = 0.0117, OR = 0.33, 95% CI: 0.17, 0.67) with bronchiectatic AD or emphysema were observed in RA.

CONCLUSION

The present study identified an association of HLA-DQB103:01 with predisposition to, and DQB103:02 with resistance to, bronchiectatic AD or emphysema in RA.

摘要

目的

类风湿关节炎（RA）患者会出现包括间质性肺疾病和气道疾病（AD）在内的慢性肺部疾病。RA中的间质性肺疾病和AD是影响RA患者生命预后的关节外表现。关于HLA等位基因与RA的关联研究已经开展，并且有报道称几个等位基因的共享表位与RA易感性相关。针对患有慢性肺部疾病的RA亚群的关联研究较少。本研究的目的是确定与包括AD存在在内的RA表型相关的HLA等位基因。

方法

分析HLA-DRB1和DQB1等位基因与RA患者慢性肺部疾病之间的关联。

结果

发现DR4血清学组与对普通间质性肺炎的抗性呈正相关[P = 0.0250，优势比（OR）0.62，95%置信区间（CI）：0.41，0.93]。DR2血清学组与普通间质性肺炎的易感性相关（P = 0.0036，OR = 1.86，95% CI：1.23，2.81）。发现共享表位等位基因与细支气管性AD相关（P = 0.0040，OR = 2.06，95% CI：1.24，3.41）。DQB103:01与支气管扩张性AD相关（P = 0.0021，校正P值（Pc） = 0.0315，OR = 1.99，95% CI：1.30，3.06），也与肺气肿相关（P = 0.0007，Pc = 0.0104，OR = 2.43，95% CI：1.49，3.95）。在综合分析中，观察到DQB103:01与支气管扩张性AD或肺气肿的易感性相关（P = 1.94×10⁻⁵，Pc = 0.0003，OR = 2.16，95% CI：1.53，3.06），而DQB1*03:02与之呈负相关（P = 0.0008，Pc = 0.0117，OR = 0.33，95% CI：0.17，0.67）。