Complement Component C1q as a Potential Diagnostic Tool for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Subtyping

Background: Routine blood analytics are systematically used in the clinic to diagnose disease or confirm individuals' healthy status. For myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a disease relying exclusively on clinical symptoms for its diagnosis, blood analytics only serve to rule out underlying conditions leading to exerting fatigue. However, studies evaluating complete and large blood datasets by combinatorial approaches to evidence ME/CFS condition or detect/identify case subgroups are still scarce. Methods: This study used unbiased hierarchical cluster analysis of a large cohort of 250 carefully phenotyped female ME/CFS cases toward exploring this possibility. Results: The results show three symptom-based clusters, classified as severe, moderate, and mild, presenting significant differences (p < 0.05) in five blood parameters. Unexpectedly the study also revealed high levels of circulating complement factor C1q in 107/250 (43%) of the participants, placing C1q as a key molecule to identify an ME/CFS subtype/subgroup with more apparent pain symptoms. Conclusions: The results obtained have important implications for the research of ME/CFS etiology and, most likely, for the implementation of future diagnosis methods and treatments of ME/CFS in the clinic.

Automated summary

This study used unbiased hierarchical cluster analysis of 250 carefully phenotyped female ME/CFS cases to identify three symptom-based clusters with significant differences in five blood parameters. Additionally, high levels of circulating complement factor C1q were found in a subgroup of participants, identifying it as a key molecule for an ME/CFS subtype with more apparent pain symptoms. These results have important implications for ME/CFS etiology research and future diagnosis and treatment methods.