Genetic susceptibility to multiple sclerosis in Sardinians: an immunological study

Objectives - We studied the in vitro production of variably MS-related cyto kines from Sardinian MS and healthy donors bearing the two "Sardinian" MS-a ssociated HLA-DR alleles: DR3 and DR4, with the purpose to evidentiate poss ible differences in their immune response. Materials and methods - ELISA we re used for detection of cellular products by mitogen-activated peripheral blood mononuclear cells. Results - PHA-activated HLA-DR4 +/DR3- mononuclear cells produce significantly higher amounts of TNF-alpha compared with the DR3 +/DR4-. In addition, homozygous HLA-DR3 + mononuclear cells from MS pat ients produce significantly lower amounts of IL-10 than those from homozygo us HLA-DR3 + healthy donors. Conclusion - The abnormal production of detrim ental or regulatory cytokines may account for the genetic susceptibility to MS in different HLA-subgroups of Sardinian MS patients.