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Previous serial measurements of lymphocyte subpopulations in individuals with multiple sclerosis (MS) have demonstrated periodic reductions in the number of OKT8 positive (T8+) cells. In this longitudinal study, involving twice monthly samples from each participant and carried out in two phases lasting at least six and three months respectively, we have confirmed that fluctuations in T8+ cells occur in patients with MS and also found a significant reduction in this lymphocyte subpopulation in patients' spouses but not their siblings, compared with unrelated controls. The changes observed in spouses were related in time to those occurring in patients on 10/13 occasions from 5/9 families; no temporal relationship occurred in the remainder. Taking two or more low T8+ values as significant, 12/13 patients, 7/9 spouses, 6/13 siblings and 4/13 controls (chi 2 = 12.5; P less than 0.01) were abnormal at some stage. Our results provide indirect evidence for the role of environmental factors in determining certain immunological abnormalities present in patients with MS and illustrate the role of family studies in determining the specificity of these changes to the disease.

results in 600 (HLA-A and -B) and 407 (HLA-DR and -DQ) randomly selected local caucasoid controls. All antigen assignments were made without prior knowledge of the disease status. The significance of associations between multiple sclerosis and particular phenotypes was examined using the chi-square test and relative risks (RR) with 95% confidence limits were calculated. Lastly, correlation coefficients between specific antigen frequencies and prevalence were computed. ResultsThere was an increased frequency of HLA-A3 (26 3% vs 24-3%:ns), -B7 (40 4% vs 28-2%:ns) and -DR2 (50 7% vs 26-5%:p < 0-001) in patients compared with controls (table 1). A similar trend was observed comparing the frequencies of HLA-DQwl in patients (n = 45, 71 1%) and controls (59%) but this was not statistically significant. The relative risk for developing multiple sclerosis in the presence of HLA-DR2 or -DQwI was 2-87 (95% confidence interval 1-66-4-98) and 1-7 (95% confidence interval 0-88-2-21) respectively. Previously published antigen frequencies and statistics for north east Scotland' are also shown in table 1. Table 2 shows the relative risk for developing multiple sclerosis in south east Wales in the presence of different combinations of class two antigens. Table 3 shows the relationship between the frequency of HLA-DR2 and -DQwI in patients and controls together with prevalence of multiple sclerosis in areas where all three variables have been studied. Although the prevalence of multiple sclerosis correlates directly with normal variations in the frequency of HLA-DR2 (r = 0-952) and -DQwl (r = 0 955) there are too few observations to achieve statistical significance.

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