Abstract:
Myalgic encephalomyelitis, also called chronic fatigue syndrome (ME/CFS), is an acquired multisystem disease. The core symptoms include fatigue, exercise intolerance and pain as well as cognitive, autonomic and immunological manifestations. The diagnosis of ME/CFS is based on clinical criteria. Specific biomarkers do not currently exist, but studies suggest a role for soluble cluster of differentiation 26 (sCD26) and autoantibodies (AAK) against G protein-coupled receptors (GPCR). In many cases, the disease begins as a result of infections.
The aim of this work was to determine the pathophysiological significance of potential biomarkers, assuming different development mechanisms in patients with infection-associated disease onset compared to those with other triggers. In a first study, sCD26, also called dipeptidyl peptidase-4 (DPP-4) due to its enzymatic activity, was analyzed and compared in the serum of 205 ME/CFS patients and 98 controls. This was followed by a comprehensive correlation analysis between sCD26 and clinical and laboratory parameters for ME/CFS patients, separated by type of disease onset. In addition, CD26 expression on lymphocyte subpopulations was determined for 12 patients and 12 controls.
In another study, a correlation analysis was carried out between AAK against vasoregulatory GPCR and symptoms in 116 ME/CFS patients, separated by type of disease onset. It was shown that in ME/CFS patients with infection-associated disease onset, sCD26 correlated with numerous immunological and metabolic parameters, the changes of which have also been described in connection with DPP-4 inhibitors. In addition, there were inverse correlations with AAK against alpha1-adrenergic and M3-acetylcholine receptors.
In this subgroup, the second study found correlations between numerous GPCR-AAK and the severity of fatigue, muscle pain and cognitive symptoms as well as greater functional impairment relevant to everyday life. None of these correlations were found in patients without infection-associated disease onset.
Here, sCD26 correlated inversely with orthostatically induced heart rate increases and AAK against alpha- and beta-adrenergic receptors with the severity of orthostatic symptoms. Different correlation patterns between AAK against GPCR and symptoms allow us to assume that in patients with ME/CFS, an altered function of the AAK or its receptors or signaling pathways has occurred as a result of an infection. The association of sCD26 and GPCR-AAK also indicates the dysregulation of other parts of the immune system with potentially pathological consequences. The differences presented compared to patients with non-infectious genesis suggest two definable subgroups.
Source: Szklarski, Marvin. Characterization of subgroups of myalgic encephalomyelitis/chronic fatigue syndrome based on disease onset, symptoms and biomarkers. Charité – University Medicine Berlin, dissertation. https://refubium.fu-berlin.de/handle/fub188/40276