Organic solvents and MS susceptibility: Interaction with MS risk HLA genes

Neurology. 2018 Jul 31;91(5):e455-e462. doi: 10.1212/WNL.0000000000005906. Epub 2018 Jul 3.

Abstract

Objective: We hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between organic solvents and MS risk human leukocyte antigen (HLA) genes.

Methods: Using a Swedish population-based case-control study (2,042 incident cases of MS and 2,947 controls), participants with different genotypes, smoking habits, and exposures to organic solvents were compared regarding occurrence of MS, by calculating odds ratios with 95% confidence intervals using logistic regression. A potential interaction between exposure to organic solvents and MS risk HLA genes was evaluated by calculating the attributable proportion due to interaction.

Results: Overall, exposure to organic solvents increased the risk of MS (odds ratio 1.5, 95% confidence interval 1.2-1.8, p = 0.0004). Among both ever and never smokers, an interaction between organic solvents, carriage of HLA-DRB1*15, and absence of HLA-A*02 was observed with regard to MS risk, similar to the previously reported gene-environment interaction involving the same MS risk HLA genes and smoke exposure.

Conclusion: The mechanism linking both smoking and exposure to organic solvents to MS risk may involve lung inflammation with a proinflammatory profile. Their interaction with MS risk HLA genes argues for an action of these environmental factors on adaptive immunity, perhaps through activation of autoaggressive cells resident in the lungs subsequently attacking the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Environmental Exposure / adverse effects*
  • Female
  • Gene-Environment Interaction*
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • HLA-A2 Antigen / genetics*
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / chemically induced
  • Multiple Sclerosis / epidemiology
  • Multiple Sclerosis / genetics*
  • Organic Chemicals / adverse effects*
  • Solvents / adverse effects
  • Sweden / epidemiology

Substances

  • HLA-A*02 antigen
  • HLA-A2 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*15 antigen
  • Organic Chemicals
  • Solvents