Natural killer cytotoxicity in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a multi-site clinical assessment of ME/CFS (MCAM) sub-study

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem illness characterized by substantial reduction in function accompanied by profound unexplained fatigue not significantly relieved by rest, post-exertional malaise, and other symptoms. Reduced natural killer (NK) cell count and cytotoxicity has been investigated as a biomarker for ME/CFS, but few clinical laboratories offer the test and multi-site verification studies have not been conducted. METHODS: We determined NK cell counts and cytotoxicity in 174 (65%) ME/CFS, 86 (32%) healthy control (HC) and 10 (3.7%) participants with other fatigue associated conditions (ill control [IC]) from the Multi-Site Clinical Assessment of ME/CFS (MCAM) study using an assay validated for samples shipped overnight instead of testing on day of venipuncture. RESULTS: We found a large variation in percent cytotoxicity [mean and (IQR) for ME/CFS and HC respectively, 34.1% (IQR 22.4–44.3%) and 33.6% (IQR 22.9–43.7%)] and no statistically significant differences between patients with ME/CFS and HC (p-value = 0.79). Analysis stratified on illness domain measured with standardized questionnaires did not identify an association of NK cytotoxicity with domain scores. Among all participants, NK cytotoxicity was not associated with survey results of physical and mental well-being, or health factors such as history of infection, obesity, smoking, and co-morbid conditions. CONCLUSION: These results indicate this assay is not ready for clinical implementation and studies are needed to further explore immune parameters that may be involved in the pathophysiology of ME/CFS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-03958-2.