title: Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitope.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, Sagamihara Hospital, National Hospital Organization, Sagamihara, Kanagawa, Japan. h-furukawa@sagamihara-hosp.gr.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Furukawa
authors.forename: Shomi
authors.initials: S
authors.lastname: Oka
authors.forename: Kota
authors.initials: K
authors.lastname: Shimada
authors.forename: Shoji
authors.initials: S
authors.lastname: Sugii
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsui
authors.forename: Tatsuoh
authors.initials: T
authors.lastname: Ikenaka
authors.forename: Hisanori
authors.initials: H
authors.lastname: Nakayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takaoka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Arinuma
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okazaki
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Futami
authors.forename: Akiko
authors.initials: A
authors.lastname: Komiya
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Migita
authors.forename: Akiko
authors.initials: A
authors.lastname: Suda
authors.forename: Shouhei
authors.initials: S
authors.lastname: Nagaoka
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D059868:HLA-DP beta-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006801:Humans; D007564:Japan; D017563:Lung Diseases, Interstitial / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012217:Rheumatoid Factor / Q000097:blood; D012307:Risk Factors
chemical_list: D000939:Epitopes; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D012217:Rheumatoid Factor