Autoimmunity-Related Risk Variants in PTPN22 and CTLA4 Are Associated With ME/CFS With Infectious Onset.

Abstract

Single nucleotide polymorphisms (SNP) in various genes have been described to be associated with susceptibility to autoimmune disease. In this study, myalgic  encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients and controls were  genotyped for five immune gene SNPs in tyrosine phosphatase non-receptor type 22  (PTPN22, rs2476601), cytotoxic T-lymphocyte-associated protein 4 (CTLA4,  rs3087243), tumor necrosis factor (TNF, rs1800629 and rs1799724), and interferon  regulatory factor 5 (IRF5, rs3807306), which are among the most important risk  variants for autoimmune diseases. Analysis of 305 ME/CFS patients and 201 healthy  controls showed significant associations of the PTPN22 rs2476601 and CTLA4  rs3087243 autoimmunity-risk alleles with ME/CFS. The associations were only found  in ME/CFS patients, who reported an acute onset of disease with an infection  (PTPN22 rs2476601: OR 1.63, CI 1.04-2.55, p = 0.016; CTLA4 rs3087243: OR 1.53, CI  1.17-2.03, p = 0.001), but not in ME/CFS patients without infection-triggered  onset (PTPN22 rs2476601: OR 1.09, CI 0.56-2.14, p = 0.398; CTLA4 rs3087243: OR  0.89, CI 0.61-1.30, p = 0.268). This finding provides evidence that autoimmunity  might play a role in ME/CFS with an infection-triggered onset. Both genes play a  key role in regulating B and T cell activation.