Multiple sclerosis in the Faroe Islands. VI. Studies of HLA markers

Occurrence of clinical neurologic multiple sclerosis (CNMS) among resident Faroese began between 1943 and 1973 and comprised three epidemics. The occupation by British forces for 5 years during World War II was interpreted to have been of major importance for the occurrence of these epidemics and led us to believe that CNMS is the rare, late result of a single, widespread, systemic and specific infectious disease which we have labelled the primary MS affection (PMSA). In this study we describe the occurrence of genetic markers of the HLA system in 16 Faroese MS patients, 25 of their siblings, 30 unrelated healthy neighbors and spouses to MS patients, 18 healthy controls from areas where no MS cases have been detected, and 80 unrelated normal Faroese. These studies show no significant deviations of HLA class I antigens, whereas the class II antigens do deviate: 50% of the Faroese MS patients carry the HLA-DR2 (DQ1/DRB 15) antigen, compared to a frequency of 15-20% among the control groups. Also the group of siblings of MS patients showed an increased frequency of DR4 (72%) compared to normal frequency among MS patients and other normal controls (43-47%). However, if DR15-positive individuals were excluded, this difference was further reduced. If PMSA was widespread within this group, DR4 or some closely associated genetic marker may confer protection against PMSA developing into CNMS. The occurrence of CNMS in these epidemics seems therefore associated to HLA class II-linked genetic factors similar to those found in studies of other caucasians with MS. This observation seems important in understanding the pathogenesis of this disease.