Thesis Characterization of subgroups in Myalgic Encephalomyelitis/CFS based on onset trigger, symptoms and biomarkers [German], 2023, Szklarski

Source: Charite University Date: November 30, 2023 URL: https://refubium.fu-berlin.de/handle/fub188/40276

https://refubium.fu-berlin.de/bitstream/handle/fub188/40276/Szklarski_Marvin_Diss.pdf

Characterization of subgroups in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome based on onset trigger, symptoms and biomarkers [German] ---------------------------------------------------------------------------
Marvin Szklarski - Medizinischen Fakultat, Charite University, Berlin, BRD

Abstract

Myalgic Encephalomyelitis, also known as Chronic Fatigue Syndrome (ME/CFS), is an acquired multisystemic disease. Symptoms include fatigue, exertion intolerance, pain as well as cognitive, autonomous and immunological manifestations. In the absence of serological biomarkers diagnosis is based on clinical criteria. Studies, however, indicate soluble cluster of differentiation 26 (sCD26) and autoantibodies (AAB) to G-protein coupled receptors (GPCR) to be involved. Disease onset is often preceded by infections. This dissertation aimed to evaluate the pathomechanistic role of potential biomarkers under the assumption of different factors driving the disease in patients with infection-triggered as compared to non-infectious ME/CFS.

In a first study, sCD26, also known as dipeptidyl-peptidase-4 (DPP-4) due to its enzymatic activity, was analyzed in serum samples of 205 ME/CFS-patients as well as 98 controls. Comprehensive, onset-stratified correlation analyzes were performed between sCD26 and clinical as well as paraclinical parameters. In addition, CD26-expression on lymphocyte subpopulations was determined for 12 ME/CFS-patients and 12 controls. A second study evaluated correlations between symptom severity and AAB to vasoregulative GPCR in 116 ME/CFS-patients stratified by onset trigger.

In ME/CFS-patients with infection-triggered onset, several correlations between sCD26 and metabolic as well as immunological parameters were found which are in line with reported effects of DPP-4-inhibitors. Further, sCD26 inversely correlated with AAB against alpha1-adrenergic and M3-acetylcholinergic receptors. In this subgroup, the second study revealed correlations between several GPCR-AAB and the severity of fatigue, muscle pain, cognitive symptoms as well as adverse outcomes in the Short Form 36 Health Survey, the Composite Autonomic Symptom Score 31 and the Bell Disability Scale. None of these correlations were found in patients without infection-triggered onset. In the latter subgroup, sCD26 inversely correlated with changes in heart rate after orthostatic challenge and AAB against alpha- and beta-adrenergic receptors correlated with the severity of orthostatic symptoms.

Distinct correlation patterns between GPCR-AAB and symptoms suggest that in the postinfectious ME/CFS-subgroup functional changes to the GPCR-AAB or their receptors and respective pathways might have occurred in response to an infection. The associations found between GPCR-AAB and sCD26 point to dysregulations of further parts of the immune system with potentially pathological implications. The results presented in this work indicate two delimitable subgroups in ME/CFS.

 

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