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

• Published in: Scientific reports Vol. 10; no. 1; p. 5267
• Main Authors: Lande, Asgeir, Fluge, Øystein, Strand, Elin B., Flåm, Siri T., Sosa, Daysi D., Mella, Olav, Egeland, Torstein, Saugstad, Ola D., Lie, Benedicte A., Viken, Marte K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.03.2020; Nature Publishing Group
• Subjects: 45; 45/23; 692/308/2056; 692/499; Adolescent; Adult; Aged; Alleles; Antigens; Autoimmune diseases; Case-Control Studies; Chronic fatigue syndrome; Drb1 protein; Encephalomyelitis; Etiology; Fatigue; Fatigue Syndrome, Chronic - genetics; Fatigue Syndrome, Chronic - immunology; Female; Genes, MHC Class I; Genes, MHC Class II; Genetic Predisposition to Disease; Genotyping; Heterogeneity; Histocompatibility antigen HLA; HLA Antigens - analysis; HLA Antigens - genetics; Humanities and Social Sciences; Humans; Immune system; Linkage Disequilibrium; Male; Middle Aged; multidisciplinary; Next-generation sequencing; Norway; Pathogenesis; Patients; Science; Science (multidisciplinary); Severity of Illness Index; Young Adult; Norway
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-62157-x

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.