Psoriasis and Susceptibility to Other Autoimmune Diseases

An Outline for the Clinician

Faisal R Ali; Richard B Warren

Disclosures

Expert Rev Clin Immunol. 2013;9(2):99-101. 

In This Article

Present: Genetic Studies

Recent advances in genetic technologies now permit the systematic interrogation of millions of markers scattered across the genome comparing their frequencies between the general population and diseases such as psoriasis. The advent of such genome-wide association studies (GWAS) has uncovered many novel associations of diseases. At least 36 genetic loci are now known to be associated with psoriasis, divided into four principal categories: innate immunity, T-cell signaling, skin barrier function and NF-κB signaling.[6,7]

These genetic studies have underlined the pan-autoimmune theorem, which purports that individuals with one autoimmune disease are predisposed genetically to other autoimmune diseases, and supports existing epidemiological data.

This characteristic has been exploited to help unearth the genetics of psoriasis. By systematically searching for known genetic risk variants associated with a range of autoimmune diseases in a cohort of psoriasis patients, researchers have recently detected novel associations of early-onset psoriasis with IL-2/21, which are cytokines implicated in T-cell homeostasis, activation and proliferation.[8] Similar systematic interrogation of known rheumatoid arthritis loci has facilitated validation of the REL locus in psoriasis and psoriatic arthritis patients.[9,10] REL encodes c-Rel, one of the members of the NF-κB family, transcription factors involved in the inflammatory response and regulation of cell survival.

Curiously, susceptibility to certain autoimmune diseases appears to impart protection to others, one such example being the REL locus that predisposes to psoriasis,[11] yet protects from development of rheumatoid arthritis.[12] The minor allele of the PTPN22 allele imparts susceptibility to rheumatoid arthritis, Type 1 diabetes and autoimmune thyroid disease, yet affords protection from Crohn's disease.[13] Taken together, these findings indicate clustering of autoimmune diseases, with antibody-mediated autoimmune diseases and autoimmune diseases associated with seronegative arthritides forming distinct groups, with presumed distinct underlying molecular pathways.[10] It is noteworthy that a different single nucleotide polymorphism within the same genetic locus may associate with different diseases, as demonstrated by the PTPN22 locus. PTPN22 encodes a protein tyrosine phosphatase that modulates responsiveness of lymphoid tissue. The R620W polymorphism imparts susceptibility to several autoimmune diseases but not to psoriasis,[14,15] while two additional single nucleotide polymorphisms at the PTPN22 locus are found to be psoriasis risk alleles.[16]

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