Why is PTPN22 a good candidate susceptibility gene for autoimmune disease?

Abstract

a b s t r a c tThe PTPN22 locus is one of the strongest risk factors outside of the major histocompatability complex that associates with autoimmune diseases. PTPN22 encodes lymphoid protein tyrosine phosphatase (Lyp) which is expressed exclusively in immune cells. A single base change in the coding region of this gene resulting in an arginine to tryptophan amino acid substitution within a polyproline binding motif associates with type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosis, Hashimotos thyroiditis, Graves disease, Addison's disease, Myasthenia Gravis, vitiligo, systemic sclerosis juvenile idiopathic arthritis and psoriatic arthritis. Here, we review the current understanding of the PTPN22 locus from a genetic, geographical, biochemical and functional perspective. Crown

Association of Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) C1858T gene polymorphism with susceptibility to autoimmune thyroid diseases: a meta-analysis

“…It has been reported that the PTPN22 locus is one of the strongest risk factors outside of the major histocompatability complex that associates with various autoimmune diseases, autoimmune thyroid diseases for example (AITDs) [25]. Despite a wealth of genetic studies implicating PTPN22 C1858T polymorphism as risk factor for AITDs, the results differed among different studies as previously mentioned, which might be partly due to different genetic backgrounds among various populations or other potential confounding factors.…”

Superresolution imaging of the cytoplasmic phosphatase PTPN22 links integrin-mediated T cell adhesion with autoimmunity

“…Interest in PTPN22 has grown considerably since initial reports of strong associations between a missense single nucleotide polymorphism in the PTPN22 gene (1858C>T, encoding R620W) and a growing number of autoimmune diseases including type I diabetes, rheumatoid arthritis and systemic lupus erythematosus (14).…”

Contribution OF Non-HLA Genes to Juvenile Idiopathic Arthritis Susceptibility

“…Кроме того, вариант Lyp 620W более чувствителен к деградации с участием цитоплазматической протеазы кальпаина, что в итоге ведет к сниженному содержанию данного варианта и гиперактивности Т и В клеток. Бла-годаря ключевой роли в иммунной регуляции наличие предрасполагающего аллеля 1858T гена PTPN22 может усиливать риск нарушения иммунной толерантности, повышенной активности дендритных клеток и индукции многочисленных аутоиммунных болезней, включая СД 1-го типа, аутоиммунный тиреоидит, системную крас-ную волчанку, ветилиго, системный склероз, миастению, РА и ЮИА [15]. IL2RA (interleukin 2 receptor alpha chain).…”