IN ADULT IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM), THE HLA-DRB1*03-ASSOCIATED INCREASED RISK FOR DEVELOPING ANTI-JO-1 ANTIBODIES IS EXACERBATED IN SMOKERS

ABSTRACT BODY: The aetiology of IIM is thought to result from the action/s of environmental risk factors in genetically susceptible individuals. HLA-DRB1*03 is known to be associated with IIM, the risk being further increased in individuals possessing anti-Jo-1 antibodies. In rheumatoid arthritis, an interaction between smoking and the shared epitope is thought to prime the development of anti-CCP antibodies.We hypothesise that in IIM an analogous interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies. 110 Caucasian IIM patients were recruited from the UK Adult Onset Myositis Immunogenetic Collaboration. IIM was confirmed as probable/definite according to Bohan & Peter (1975), and stratified by disease subtype (polymyositis [PM], dermatomyositis [DM], myositis/connective tissue disease [CTD]-overlap). DNA was genotyped at DRB1 using a commercial sequence specific oligonucleotide kit. Anti-Jo-1 antibody status was established using immunoprecipitation.A retrospective smoking history was obtained prior to the onset of IIM. Of the 110 patients assessed, sub-group numbers were as follows: PM, n=43; DM, n=47; myositis/overlap, n=20; females 64%, median age of disease onset 47+/-14.2 years. 59 (53.6%) patients admitted to having ever smoked. Of the 59 smokers, 22 (37%) had DM, 27 (46%) had PM and 10 (17%) had myositis/CTD-overlap. HLA and serologic data was available in 97 patients. No significant association was observed between smoking and anti-Jo-1 status (25% Jo-1 positive smokers vs. 20% Jo-1 positive non-smokers, p=0.63). HLA-DRB1*03 was significantly associated with anti-Jo-1 status, with an increased frequency in DRB1*03 positive compared to DRB1*03 negative cases (82% vs. 43%, odds ratio 6.0, 95% confidence interval 1.8-20.0, p=0.003), even after adjustment for age at myositis onset and gender. DRB1*03 negative smokers appeared less at risk of developing anti-Jo-1 than DRB1*03 negative non-smokers (Table 1). There was an increased frequency of anti-Jo-1 in DRB1*03 positive smokers vs. DRB1*03 positive non-smokers (44% vs. 26%, p=0.17). A significant association was noted between DRB1*03 positive smokers and the remainder of the cases (44% vs. 14%, OR 4.8, 1.5-14.9, p=0.001). A non-significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure (OR 9.4, 0.67-131, p=0.09). 1. There was a high prevalence of smoking in patients with IIM. 2.Smoking appears to be associated with an increased risk for the development of anti-Jo-1 antibodies in HLA-DRB1*03 positive IIM cases. Jo-1 positive Jo-1 negative OR/95% CI Never smoked/DRB1*03 neg 3 18 1.0 Never smoked/DRB1*03 pos 6 17 2.1,0.4-14.9 Smoker/DRB1*03 neg 1 25 0.2,0.004-3.4 Smoker/DRB1*03 pos 1 15 4.8,1-30.4