Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. — CFSMEATLAS
Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Szklarski, Marvin, Freitag, Helma, Lorenz, Sebastian et al. · Frontiers in immunology · 2021 · DOI
Quick Summary
This study looked at a protein called sCD26 in people with ME/CFS to understand how it relates to immune system problems and heart function issues. Researchers found that people with ME/CFS triggered by an infection had different patterns of immune problems linked to low sCD26 levels compared to people whose ME/CFS started without an infection. The findings suggest that infection-related and non-infection-related ME/CFS may involve different biological mechanisms.
Why It Matters
This research provides evidence that infection-triggered and non-infection-triggered ME/CFS may have distinct biological pathways, which could eventually lead to personalized diagnostic or therapeutic approaches. Understanding these different mechanisms is crucial for developing targeted treatments and explaining why patients experience similar symptoms through different underlying processes.
Observed Findings
Significantly lower sCD26 concentrations found only in female ME/CFS patients, not males
In infection-triggered ME/CFS: low sCD26 correlated with elevated autoantibodies against alpha-1 adrenergic and M3 muscarinic acetylcholine receptors
In infection-triggered ME/CFS: low sCD26 associated with activated T cells, elevated liver enzymes, creatine kinase, and lactate dehydrogenase, plus inverse association with IL-1β
In non-infection-triggered ME/CFS: low sCD26 associated with elevated resting heart rate after orthostatic challenge and POTS diagnosis
Inferred Conclusions
Infection-triggered and non-infection-triggered ME/CFS involve different pathomechanisms, with infection-triggered disease involving autoimmune-mediated vascular and immune dysregulation
sCD26/DPP-4 enzymatic activity appears linked to immune regulation in infection-triggered ME/CFS but to orthostatic regulation in non-infection-triggered ME/CFS
The enzyme sCD26 plays a role in multiple ME/CFS pathophysiological processes including T cell activation, autoimmune responses, and cardiovascular regulation
Remaining Questions
Why do only female patients show significantly lower sCD26 levels, and what role does sex/hormonal status play in this association?
Does low sCD26 contribute to disease pathology or is it a consequence of underlying ME/CFS processes?
What This Study Does Not Prove
This study does not prove that sCD26 is a reliable diagnostic marker for ME/CFS, as lower levels were only consistently found in females. The correlations identified do not establish causation—low sCD26 may be a consequence rather than a cause of ME/CFS pathology. The findings also cannot be generalized beyond the study population without replication in independent cohorts.