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

Abstract

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.

Personalized Management of Fatigue in Individuals With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID Using a Smart Digital mHealth Solution: Protocol for a Participatory Design Approach

“…Fatigue is recognized as one of the most common symptoms in individuals with chronic postviral conditions. It is defined as the early onset of tiredness after starting an activity, a feeling of exhaustion or difficulty in carrying out a physical (physical fatigue) or cognitive (cognitive fatigue) task, which is not recovered after a rest [1]. It is relevant to highlight several issues included in this definition.…”

“…Finally, fatigue is essentially a subjective condition, encompassing feelings or difficulties. Thus, it is linked to perceived fatigue, which is defined as the subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities [1]. Myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS) and post-COVID-19 syndrome or postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, are multisystem postviral conditions where chronic fatigue is present as the most common disabling symptom.…”

A comparative study of valaciclovir, valganciclovir, and artesunate efficacy in reactivated HHV‐6 and HHV‐7 infections associated with chronic fatigue syndrome/myalgic encephalomyelitis

“…Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), remains a serious, potentially disabling, common condition in the population and difficult to treat 1 . Developing effective methods to treat this serious disease is a priority task for modern medicine 2 . One of the recent achievements in understanding the pathogenesis of ME/CFS is the identified association of this neuropsychiatric disorder with reactivated herpesvirus infections, especially with human herpesviruses types 6 and 7 (HHV‐6 and HHV‐7) 3,4 .…”

“…1 Developing effective methods to treat this serious disease is a priority task for modern medicine. 2 One of the recent achievements in understanding the pathogenesis of ME/CFS is the identified association of this neuropsychiatric disorder with reactivated herpesvirus infections, especially with human herpesviruses types 6 and 7 (HHV-6 and HHV-7). 3,4 Evidence for this association is based on serological tests that demonstrate an immune response to viral proteins associated with reactivation and intensive reproduction 5,6 and blood leukocyte PCR results 7,8 of affiliated populations (PCR, Biocom, Russian Federation).…”

Special Issue “Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: Diagnosis and Treatment”

“…A potential blood diagnostic tool, by Castro-Marrero J. and his Spanish collaborators, could be the complement C1 examining in CFS/ME three-symptom clusters, identified as severe, moderate and mild, presenting important differences in five blood parameters [ 12 ]. Another objective measurement for PEM, which is a hallmark of CFS/ME, is the application of the two-days cardiopulmonary exercise test (CPET) to assess functional impairment: Eun-Jin Lim and Korean collaborators, in their paper, published the results of a meta-analysis on this diagnostic tool [ 13 ].…”