Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS.
Milivojevic, Milica, Che, Xiaoyu, Bateman, Lucinda et al. · PloS one · 2020 · DOI
Quick Summary
Researchers studied blood proteins in ME/CFS patients and healthy controls to look for disease markers. They found that certain immune-related proteins, particularly immunoglobulin proteins (which are part of the immune system), were abnormal in ME/CFS patients and could help identify who has the disease. The results suggest ME/CFS involves an overactive or dysregulated immune response.
Why It Matters
This study provides objective biomarkers that could improve ME/CFS diagnosis, which currently relies on symptom assessment alone. Identifying immune dysregulation as a core feature may guide future treatment strategies targeting B cell dysfunction. The finding that proteomic profiles differ between ME/CFS with and without IBS suggests biological heterogeneity worth investigating further.
Observed Findings
IGHV3-23/30 was significantly associated with ME/CFS in logistic regression analysis.
Immunosubtype-specific patterns emerged: IGHV3-23/30 and kappa variable region 3-11 associated with ME/CFS without IBS; immunoglobulin lambda constant region 7 showed quadratic association with ME/CFS with IBS.
Machine learning models predicted ME/CFS status with AUC 0.774-0.838 overall, AUC 0.806-0.846 for ME/CFS+IBS, and AUC 0.754-0.780 for ME/CFS without IBS.
Proteomic signatures were specific enough to distinguish between ME/CFS patients with and without IBS comorbidity.
Inferred Conclusions
ME/CFS is associated with antigen-driven clonal B cell expansion, indicating immune dysregulation as a key pathophysiological feature.
Plasma proteome analysis, particularly immunoglobulin profiling, can serve as a biomarker source for objective ME/CFS diagnosis and disease stratification.
IBS comorbidity in ME/CFS may reflect distinct immunological subtypes, suggesting biological heterogeneity within the ME/CFS population.
Remaining Questions
What specific antigens are driving the B cell clonal expansion observed in ME/CFS patients?
Are these proteomic abnormalities present at disease onset or do they develop over time, and are they reversible with treatment?
What This Study Does Not Prove
This study does not prove that abnormal immunoglobulins cause ME/CFS—only that they are associated with the disease. It does not establish whether these immune changes represent the primary disease mechanism or are secondary consequences of the illness. The study cannot be generalized to the broader ME/CFS population without validation in larger, more diverse cohorts.