Background Previous studies on the influence of exposure to organic solvents on multiple sclerosis (MS) risk have yielded inconclusive results.

Aim To investigate the relationship between exposure to organic solvents and MS risk, and the potential interaction between organic solvents and MS HLA risk genes.

Methods We analysed data from a Swedish population-based case-control study with incident cases of MS (2042 cases, 2947 controls). Subjects with different genotypes, smoking habits, and organic solvents exposure were compared with regard to occurrence of MS, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. A potential interaction between exposure to organic solvents and the HLA MS risk genes was evaluated by calculating attributable proportion due to interaction (AP).

Results Overall, exposure to organic solvents increased the risk of MS (OR 1.5, 95% CI: 1.2–1.8, p = 0.0004). A significant three way interaction between exposure to organic solvents, carriage of HLA-DRB1*15 and absence of HLA-A*02 was observed with regard to MS risk (AP 0.6, 95% CI: 0.3–0.8). Among HLA-DRB1*15 positive subject without the protective HLA-0*02 allele, there was also a significant interaction between organic solvents and smoking (AP 0.7, 95% CI: 0.4–1.0), whereas no significant interaction was observed among those with low genetic risk.Subjects exposed to smoking and organic solvents carrying HLA-DRB1*15 and lacking HLA-A*02 had a 30-fold increased risk of developing MS compared with non-exposed subjects without the genetic risk factors (OR 30.3, 95% CI: 11.7–78.3).

Conclusions Among subjects with a genetic susceptibility, it seems like different sources of lung irritation contribute to the development of MS. We hypothesise that different sources of lung irritation may contribute to elicit an immune reaction against modified self-proteins or against potentially auto-aggressive cells resident in the lungs, and subsequently lead to MS in people with a genetic susceptibility to MS.