HLA and the response of lymphocytes to viral antigens in patients with multiple sclerosis

Serum antiviral antibody titers, presence of lymphocytotoxic antibodies, and lymphoproliferative responses to viral antigens were determined in 44 multiple sclerosis (MS) patients and 25 healthy subjects. These measurements were correlated with the HLA type and the clinical characteristics of the patients. The Dw2/DR2 phenotype, known to be associated with increased MS susceptibility, was also associated with a later onset of MS and more rapid progression of disease. Within the Dw2/DR2 group, the disability status and rate of progression did not correlate with the relative degree of lymphoproliferative response. Patients with the Dw2/DR2 phenotype had similar lymphoproliferative responses to all viral antigens as control subjects possessing or lacking Dw2/DR2. Patients lacking Dw2/DR2 had increased lymphoproliferative responses selectively to measles virus when compared with normal subjects or Dw2/DR2 positive individuals. Absence of the B40 antigen was associated with high antibody titer to measles, and presence of the Dw7/DR7 antigens was associated with high titers against herpes simplex I virus. Both B40 and Dw7/DR7 phenotypes were associated with decreased occurrence of lymphocytotoxic antibodies. The Dw7/DR7 phenotype has been associated in previous studies with a decreased susceptibility to MS. These results, therefore, suggest that both humoral and cellular antiviral immune mechanisms in man are under the influence of HLA-linked genes. Progressive or lack of progression in MS could in turn be somehow related to the differing strength of antiviral immune responses in individuals of the appropriate HLA genotype.