The importance of epistatic interactions in the development of autoimmunity.

Genetic predisposition is the main element in susceptibility to a variety of autoimmune diseases, including systemic lupus erythematosus (SLE). Epistatic interactions between susceptibility loci play a major role in the progression of autoimmunity, as our recent work, associating a common haplotype of the SLAM/CD2 receptor family with autoimmune susceptibility in specific genomic contexts, has illustrated. Furthermore, these interactions can be abrogated in the presence of appropriate modifier loci. We postulate that susceptibility to autoimmunity may be a consequence of imbalances in immune regulation that are elicited by specific combinations of common alleles at multiple, immunoregulatory loci.