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Published on: October 22, 2020
Interaction between smoking and HLA-A*02:01 in multiple sclerosis progression
Anna Karin Hedström1, Pernilla Stridh1, Jan Hillert1
1Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Multiple Sclerosis (Houndmills, Basingstoke, England)
|July 3, 2026
Summary
Smoking increases multiple sclerosis (MS) disability progression risk, particularly in those without HLA-A*02:01. This highlights how immunogenetics influence MS outcomes in smokers.
Area of Science:
- Immunogenetics
- Neurology
- Environmental Health
Background:
- Gene-environment interactions, specifically between smoking and HLA genotypes, are implicated in multiple sclerosis (MS) susceptibility.
- The influence of these interactions on MS disability progression remains largely uncharacterized.
Purpose of the Study:
- To investigate if smoking affects MS disability progression differently based on HLA-A*02:01 and HLA-DRB1*15:01 status.
- To explore gene-environment interactions in MS beyond initial disease onset.
Main Methods:
- Utilized two population-based case-control cohorts with 6807 MS patients from the Swedish MS registry.
- Classified patients by smoking status at diagnosis and HLA genotype (HLA-A*02:01, HLA-DRB1*15:01).
- Employed Cox regression to assess time to disability worsening (24-week confirmed disability worsening, EDSS 3, 4, 6), analyzing interaction on the additive scale over 15 years.
Main Results:
- Smoking at diagnosis significantly increased disability progression risk (CDW, EDSS 3, EDSS 4) primarily in individuals lacking HLA-A*02:01.
- Smokers positive for HLA-A*02:01 showed no clear increased risk of disability progression.
- No significant interaction was detected between smoking and HLA-DRB1*15:01 status regarding MS disability progression.
Conclusions:
- The effect of smoking on multiple sclerosis progression is contingent upon an individual's immunogenetic background, specifically HLA-A*02:01 status.
- These findings underscore the importance of considering genetic factors when evaluating environmental risks in MS.
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