The HLA-B8, DR3 haplotype is remarkable for its association with a number of autoimmune diseases such as lupus, type I diabetes mellitus and IgA deficiency. The extended HLA-B8, DR3 haplotype is highly conserved and in linkage disequilibrium with the tumour nectrosis factor (TNF*2) promoter allele which leads to a genetically high setting of TNF-α and C4AQ0, which leads to defect in opsonization and clearance of immune complexes. Studies in healthy individuals have revealed an altered balance of cytokines produced in carries of the haplotype such an impaired production of IL-2, IL-5, IL-12 and INF-γ after a mitogen stimulus. The immune response is thus skewed towards Th2 cytokine production and the humoral response, although IL-5 production is also deperessed. Furthermore, both an increased production of autoantibodies and an increased blood lymphocyte spontaneous apoptosis are observed resulting in low levels of circulating lymphocytes.
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