Gene Expression Subtypes in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined.We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diag-nosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using amicroarraywith a cutoff fold difference of expression of2.5. Genes showing differential expres-sionwere further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymer-ase chain reaction. Differential expressionwas confirmed for 88 genes; 85were upregulated, and 3were downreg-ulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reac-tion data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity. Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterized by severe and debilitating fa