Immunogenetic risk and protective factors for the development of L-tryptophan-associated eosinophilia-myalgia syndrome and associated symptoms.

OBJECTIVE

To assess L-tryptophan (LT) dose, age, sex, and immunogenetic markers as possible risk or protective factors for the development of LT-associated eosinophilia-myalgia syndrome (EMS) and related clinical findings.

METHODS

HLA-DRB1 and DQA1 allele typing and Gm/Km phenotyping were performed on a cohort of 94 white subjects with documented LT ingestion and standardized evaluations. Multivariate analyses compared LT dose, age, sex, and alleles among groups of subjects who ingested LT and subsequently developed surveillance criteria for EMS, developed EMS or characteristic features of EMS (EMS spectrum disorder), or developed no features of EMS (unaffected).

RESULTS

Considering all sources of LT, higher LT dose (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 1.1-1.8), age >45 years (OR 3.0, 95% CI 1.0-8.8), and HLA-DRB103 (OR 3.9, 95% CI 1.2-15.2), DRB104 (OR 3.9, 95% CI 1.1-16.4), and DQA10601 (OR 13.7, 95% CI 1.3-1.8) were risk factors for the development of EMS, whereas DRB107 (OR 0.12, 95% CI 0.02-0.48) and DQA10501 (OR 0.23, 95% CI 0.05-0.85) were protective. Similar risk and protective factors were seen for developing EMS following ingestion of implicated LT, except that DRB103 was not a risk factor and DQA10201 was an additional protective factor. EMS spectrum disorder also showed similar findings, but with DRB104 being a risk factor and DRB107 and DQA10201 being protective. There were no differences in sex distribution, Gm/Km allotypes, or Gm/Km phenotypes among any groups.

CONCLUSION

In addition to the xenobiotic dose and subject age, polymorphisms in immune response genes may underlie the development of certain xenobiotic-induced immune-mediated disorders, and these findings may have implications for future related epidemics.