The effect of cigarette smoking on the clinical and serological phenotypes of polymyositis and dermatomyositis.

OBJECTIVE: Cigarette smoking is associated with immune-mediated disorders. We explored the contribution of smoking to polymyositis (PM) and dermatomyositis (DM) phenotypes and attempted to determine whether cigarette smoking effects differ by race and genotype. METHODS: Associations of tobacco smoking with disease features, autoantibodies, HLA types, and race were evaluated using multiple logistic regressions in 465 patients. RESULTS: Caucasian ever-smokers (n = 140) were more likely to have PM (adjusted OR = 2.24, 95% CI: 1.41\x963.57), anti-synthetase (adjusted OR = 1.93, 95% CI: 1.12\x963.34) and anti-Jo-1 autoantibodies (adjusted OR = 1.94, 95% CI: 1.08\x963.46) and less likely to have anti-p155/140 autoantibodies (adjusted OR = 0.36, 95% CI: 0.14\x960.92). In Caucasians, ever-smokers had a greater interstitial lung disease (ILD) frequency than never-smokers, while in African-Americans this relationship was inverted, but neither trend reached statistical significance. Pack-years of cigarette smoking showed significant positive associations with PM (adjusted OR = 1.02, 95% CI: 1.002\x961.04) and ILD (adjusted OR = 1.02, 95% CI: 1.001\x961.03) and was inversely associated with anti-p155/140 autoantibodies (adjusted OR = 0.93, 95% CI: 0.87\x960.99) in Caucasians. Caucasian heavy smokers (=20 pack-years) were more likely to have PM (adjusted OR = 2.52, 95% CI: 1.25\x965.09), ILD (adjusted OR = 2.48, 95% CI: 1.23\x965.00) and anti-Jo-1 autoantibodies (adjusted OR = 2.65, 95% CI: 1.16\x966.08) than never-smokers. In Caucasians, compared to never-smokers without HLA-DRB1*03:01 allele, ever-smokers with HLA-DRB1*03:01 allele had the highest odds of PM, ILD, ASA, and anti-Jo-1 autoantibodies. Risks for those with only one of these two factors were intermediate. An inverse pattern was observed regarding anti-p155/140 autoantibodies. CONCLUSION: Tobacco smoking was associated with clinical and autoantibody phenotypes in Caucasians. Our findings also suggest possible interactions among HLA-DRB1*03:01 and smoking on the risk of PM and ILD, as well as, anti-synthetase, anti-Jo-1, and anti-p155/140 autoantibodies in Caucasians.

HLA-DQA1 is not an apparent risk factor for microchimerism in patients with various autoimmune diseases and in healthy individuals.

OBJECTIVE: Microchimeric cells have been identified in lesions and peripheral blood of patients with systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), and HLA-DQA1*0501 is a risk factor for these diseases in some populations. Furthermore, DQA1*0501 has been associated with T lymphocyte microchimerism in SSc. To better define the strength of this association, we assessed the relationship among DQA1 alleles and microchimerism. METHODS: DNA from whole peripheral blood or magnetically sorted T cells was tested for microchimeric cells by polymerase chain reaction of the Y chromosome or of HLA-Cw in 87 SSc patients, 28 juvenile IIM patients, and 88 healthy controls. Thirty-seven mother-son pairs were also analyzed for microchimerism and DQA1*0501. RESULTS: We were unable to demonstrate that DQA1*0501 is associated with microchimerism in T lymphocytes or in whole peripheral blood DNA in patients with SSc or juvenile IIM or in healthy individuals. In the 37 mother-son pairs, we were unable to demonstrate an association of DQA1*0501 with microchimerism in peripheral blood DNA or T lymphocytes, and compatibility between the donor's and recipient's HLA alleles did not influence microchimerism in the recipient. CONCLUSION: These data suggest that HLA-DQA1 alleles do not appear to play a role in the persistence of microchimerism in the peripheral blood or T lymphocytes of patients with selected autoimmune diseases or in healthy individuals.