title: Association of human leukocyte antigen alleles with chronic lung diseases in rheumatoid arthritis.
abstract: 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.
  
  
  
  Associations of HLA-DRB1 and DQB1 alleles with chronic lung diseases in RA were analysed.
  
  
  
  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). 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 were observed in RA.
  
  
  
  The present study identified an association of HLA-DQB1*03:01 with predisposition to, and DQB1*03:02 with resistance to, bronchiectatic AD or emphysema in RA.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara.
authors.forename: Shomi
authors.initials: S
authors.lastname: Oka
authors.affiliation: 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 furukawa-tky@umin.org.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.affiliation: Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, Fuchu.
authors.forename: Kota
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Rheumatology, Yokohama Minami Kyosai Hospital.
authors.forename: Shoji
authors.initials: S
authors.lastname: Sugii
authors.affiliation: Department of Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashimoto
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara.
authors.forename: Akiko
authors.initials: A
authors.lastname: Komiya
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.affiliation: Department of Rheumatology, Yokohama Minami Kyosai Hospital Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama.
authors.forename: Akiko
authors.initials: A
authors.lastname: Suda
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tsunoda
authors.affiliation: Department of Rheumatology, Niigata Rheumatic Center, Shibata.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Internal Medicine, Nagoya Medical Center, National Hospital Organization, Nagoya.
authors.forename: Masao
authors.initials: M
authors.lastname: Katayama
authors.affiliation: Department of Rheumatology, Kumamoto Shinto General Hospital, Kumamoto.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Orthopedics/Rheumatology, Miyakonojo Hospital, National Hospital Organization, Miyakonojo.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Saisho
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sano
authors.affiliation: Clinical Research Center, Nagasaki Medical Center, National Hospital Organization, Omura, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.affiliation: Department of Rheumatology, Yokohama Minami Kyosai Hospital.
authors.forename: Shouhei
authors.initials: S
authors.lastname: Nagaoka
authors.affiliation: Molecular and Genetic Epidemiology Laboratory, Faculty of Medicine, University of Tsukuba, Tsukuba.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara.
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
mesh_terms: D000368:Aged; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000235:genetics; D000939:Epitopes; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011656:Pulmonary Emphysema / Q000235:genetics*
chemical_list: D000939:Epitopes; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: CT scanning; MHC; immunogenetics and HLA; respiratory; rheumatoid arthritis