Genetic susceptibility to multiple sclerosis (MS) in Caucasians was previously shown to be correlated to the presence of given alleles at the HLA-DR and Gm loci. We now demonstrate that the humoral immune response in MS central nervous system (CNS) is modulated by both loci: the levels of IgG1 subclass and IgG1 allotypes in cerebrospinal fluid of MS patients depend on both their Gm genotype and their HLA-DR2 or HLA-DR7 phenotype. That HLA-DR molecules may either participate in a preferential recruitment of IgG1 allotype-producing B cells in MS CNS or act after such a selective homing is discussed. These results demonstrate that both HLA and Gm loci are synergistically involved in the modulation of the humoral immune response.

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