title: Interaction of HLA-DRB1*03 and smoking for the development of anti-Jo-1 antibodies in adult idiopathic inflammatory myopathies: a European-wide case study.
abstract: OBJECTIVE
  HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. This study examined whether smoking was associated with the development of anti-Jo-1 antibodies in HLA-DRB1*03-positive IIM.
  
  
  METHODS
  IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation.
  
  
  RESULTS
  557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strong association between HLA-DRB1*03 and anti-Jo-1 status was observed across all four cohorts (DRB1*03 frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR 5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency of HLA-DRB1*03 was increased in smokers. The frequency of anti-Jo-1 was increased in DRB1*03-positive smokers vs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75, 95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positive non-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers and non-smokers was not significantly different. No significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure.
  
  
  CONCLUSIONS
  Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.
authors.affiliation: Rheumatic Diseases Centre, The University of Manchester, Salford Royal NHS Foundation Trust, Salford, UK.
authors.forename: H
authors.initials: H
authors.lastname: Chinoy
authors.forename: S
authors.initials: S
authors.lastname: Adimulam
authors.forename: F
authors.initials: F
authors.lastname: Marriage
authors.forename: P
authors.initials: P
authors.lastname: New
authors.forename: M
authors.initials: M
authors.lastname: Vincze
authors.forename: E
authors.initials: E
authors.lastname: Zilahi
authors.forename: A
authors.initials: A
authors.lastname: Kapitány
authors.forename: A
authors.initials: A
authors.lastname: Gyetvai
authors.forename: L
authors.initials: L
authors.lastname: Ekholm
authors.forename: P
authors.initials: P
authors.lastname: Novota
authors.forename: M
authors.initials: M
authors.lastname: Remakova
authors.forename: P
authors.initials: P
authors.lastname: Charles
authors.forename: N J
authors.initials: NJ
authors.lastname: McHugh
authors.forename: L
authors.initials: L
authors.lastname: Padyukov
authors.forename: L
authors.initials: L
authors.lastname: Alfredsson
authors.forename: J
authors.initials: J
authors.lastname: Vencovsky
authors.forename: I E
authors.initials: IE
authors.lastname: Lundberg
authors.forename: K
authors.initials: K
authors.lastname: Danko
authors.forename: W E
authors.initials: WE
authors.lastname: Ollier
authors.forename: R G
authors.initials: RG
authors.lastname: Cooper
mesh_terms: D000328:Adult; D017668:Age of Onset; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009220:Myositis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: D000974:Antibodies, Antinuclear; D059811:HLA-DRB1 Chains; C046750:Jo-1 antibody