Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Abstract

The etiology and pathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are unknown, and autoimmunity is one of many proposed  underlying mechanisms. Human Leukocyte Antigen (HLA) associations are hallmarks  of autoimmune disease, and have not been thoroughly investigated in a large  ME/CFS patient cohort. We performed high resolution HLA -A, -B, -C, -DRB1, -DQB1  and -DPB1 genotyping by next generation sequencing in 426 adult, Norwegian ME/CFS  patients, diagnosed according to the Canadian Consensus Criteria. HLA  associations were assessed by comparing to 4511 healthy and ethnically matched  controls. Clinical information was collected through questionnaires completed by  patients or relatives. We discovered two independent HLA associations, tagged by  the alleles HLA-C*07:04 (OR 2.1 [95% CI 1.4-3.1]) and HLA-DQB1*03:03 (OR 1.5 [95%  CI 1.1-2.0]). These alleles were carried by 7.7% and 12.7% of ME/CFS patients,  respectively. The proportion of individuals carrying one or both of these alleles  was 19.2% in the patient group and 12.2% in the control group (OR 1.7 [95% CI  1.3-2.2], p(nc) = 0.00003). ME/CFS is a complex disease, potentially with a  substantial heterogeneity. We report novel HLA associations pointing toward the  involvement of the immune system in ME/CFS pathogenesis.