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 (<i>PTPN22</i>, rs2476601), cytotoxic T-lymphocyte-associated protein 4 (<i>CTLA4</i>, rs3087243), tumor necrosis factor (<i>TNF</i>, rs1800629 and rs1799724), and interferon regulatory factor 5 (<i>IRF5</i>, 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 <i>PTPN22</i> rs2476601 and <i>CTLA4</i> 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 (<i>PTPN22</i> rs2476601: OR 1.63, CI 1.04-2.55, <i>p</i> = 0.016; <i>CTLA4</i> rs3087243: OR 1.53, CI 1.17-2.03, <i>p</i> = 0.001), but not in ME/CFS patients without infection-triggered onset (<i>PTPN22</i> rs2476601: OR 1.09, CI 0.56-2.14, <i>p</i> = 0.398; <i>CTLA4</i> rs3087243: OR 0.89, CI 0.61-1.30, <i>p</i> = 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.