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

Abstract

Objectives. Chronic lung diseases including interstitial lung disease and airway disease (AD) occur in RApatients. Interstitial lung disease and AD in RA are extra-articular manifestations that influence the prognosisquoad vitam of RA. Studies on associations of HLA alleles with RA have been carried out, andshared epitopes of several alleles are reported to be associated with RA susceptibility. Few associationstudies in RA subpopulations with chronic lung diseases have been conducted. The aim of the study wasto 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 usualinterstitial pneumonia [P = 0.0250, odds ratio (OR) 0.62, 95% CI: 0.41, 0.93]. The DR2 serological groupwas 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). DQB1*03:01 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 DQB1*03:01(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 wereobserved in RA.Conclusion. The present study identified an association of HLA-DQB1*03:01 with predisposition to, andDQB1*03:02 with resistance to, bronchiectatic AD or emphysema in RA.