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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.

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