AUTHOR=Steiner Sophie , Becker Sonya C. , Hartwig Jelka , Sotzny Franziska , Lorenz Sebastian , Bauer Sandra , Löbel Madlen , Stittrich Anna B. , Grabowski Patricia , Scheibenbogen Carmen 

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00578

DOI=10.3389/fimmu.2020.00578

ISSN=1664-3224

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