OBJECTIVE: The objective of this study was to evaluate for up to 7 years the prevalence of autoimmune disorders among naïve (untreated) multiple sclerosis family members compared with a contemporary general control population in Northern Greece, in a prospective case-control study, and to examine the possible relationship between immunomodulatory treatment and the appearance of additional autoimmune disorders.
METHODS: The patients and controls enrolled comprised 1383 patients with definite MS and 4392 relatives in their families and a total of 452 controls families with 1652 members.
RESULTS: At baseline, 891 multiple sclerosis families with 3112 members (73 multiplex multiple sclerosis families with 292 members and 818 simplex families with 2820 members) and 355 control families with 1580 members were examined regarding whether they had any of 12 autoimmune diseases. The baseline affected multiplex plus simplex multiple sclerosis families, the family members and the coexistent additional autoimmune disorders were higher compared with controls. There was an increase in longitudinally affected multiple sclerosis families, multiple sclerosis family members and coexistent additional autoimmune disorders compared with respective findings at the baseline observation. Comparison analysis between two time point observations (after a mean 7.1 +/- 2.2 years) for each autoimmune disorder in overall multiple sclerosis family members revealed increased rates for longitudinal autoimmune Hashimoto's thyroiditis, Graves' disease, insulin-dependent diabetes mellitus, psoriasis and vitiligo (p = 0.02, p = 0.006, p = 0.0004, p = 0.05, and p = 0.05, respectively). Some 145 newly developed, longitudinally definite autoimmune cases were recognized in multiplex plus simplex multiple sclerosis families; 116 (80%) of these disorders were observed in patients with multiple sclerosis treated with immunomodulatory medications, and 68 of these 116 (58.6%) cases exhibited baseline positive autoreactive antibodies. Binary logistic regression analysis revealed that immunotherapy predisposes to autoimmunity (odds ratio 2.8, p < 0.001) independently of the presence of baseline autoantibodies and patients' gender.
CONCLUSIONS: There is a longitudinally increased frequency of additional autoimmune disorders among multiple sclerosis family members, probably related to immunomodulatory therapy.