The Genetics of Psoriasis and Autoimmunity

Psoriasis is an inflammatory/autoimmune disease and, as with many autoimmune diseases, is associated with alleles from the major histocompatibility complex (MHC). With psoriasis and autoimmune disease, the penetrance of the MHC-associated alleles is never 100%, even for monozygotic twins. This may be because development requires additional environmental and/or genetic modifiers or requires specific T-cell receptor arrangements. Families segregating single or multilocus susceptibility alleles other than the MHC have also been reported. Overlapping genetic locations of loci for different autoimmune diseases have been known for several years and are starting to reveal common genes or genetic variants. These include genes normally involved in preventing spontaneous T-cell activation or proliferation, immune synapse formation, or cytokine production via pathways such as those mediated by NFkappaB and those involved in thymic selection. Autoimmunity may also involve dysregulation of genes or pathways regulated by the RUNX family of transcription factors. RUNX is involved in hematopoietic cell development, development of T cells in the thymus, chromatin remodeling, and gene silencing. Hence, its effect on cells of the immune system may be due to variable changes in gene expression and could account for variable body surface involvement and waxing and waning of disease.