The molecular genetics of systemic lupus erythematosus and Sjögren's syndrome.

With recent advances in understanding of the organization, complexity, and function of the major histocompatibility complex and other genes involved in the immune response, a rational approach to interpreting associations of systemic lupus erythematosus and Sjögren's syndrome with these genes is now possible. For example, both systemic lupus erythematosus and Sjögren's syndrome appear to be heterogeneous syndromes comprised of different major histocompatibility complex-mediated (and perhaps T-cell receptor-and immunoglobulin genes-mediated) autoantibody responses. Moreover, HLA class II associations with systemic lupus erythematosus- and Sjögren's syndrome-linked autoantibody responses seem to be better explained by specific amino acid residues or epitopes on these class II heterodimers, residues or epitopes putatively involved in the binding and presentation of processed antigen to the T-cell receptor that can be shared by different class II alleles. These basic themes underlie this review of recent work in the immunogenetics of these autoimmune diseases.