Evidence of a Novel Mitochondrial Signature in Systemic Sclerosis Patients with Chronic Fatigue Syndrome.

Symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are common in rheumatic diseases, but no studies report the frequency of these in early systemic sclerosis. There are no known biomarkers that can distinguish between patients with ME/CFS, although mitochondrial abnormalities are often demonstrated. We sought to assess the prevalence of ME/CFS in limited cutaneous SSc (lcSSc) patients early in their disease (<5 years from the onset of non-Raynaud's symptoms) and to determine if alterations in mitochondrial electron transport chain (ETC) transcripts and mitochondrial DNA (mtDNA) integrity could be used to distinguish between fatigued and non-fatigued patients. All SSc patients met ACR/EULAR classification criteria. ME/CFS-related symptoms were assessed through validated questionnaires, and the expression of ETC transcripts and mtDNA integrity were quantified via qPCR. SSc patients with ME/CFS could be distinguished from non-fatigued patients through ETC gene analysis; specifically, reduced expression of ND4 and CyB and increased expression of Cox7C. ND4 and CyB expression correlated with indicators of disease severity. Further prospective and functional studies are needed to determine if this altered signature can be further utilized to better identify ME/CFS in SSc patients, and whether ME/CFS in early SSc disease could predict more severe disease outcomes.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia: PR3-versus MPO-ANCA-associated vasculitis, an exploratory cross-sectional study.

Background: Persistent fatigue is a common complaint in ANCA-vasculitis (AAV) patients and has a profound impact on patient's quality of life. The symptoms associated with this fatigue mirror those found in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia. Etiologic and pathophysiologic differences exist between PR3- and MPO-ANCA disease, yet differences in their fatigue manifestations have not been well researched. We compared fatigue and its associations in healthy controls, AAV patients and fibromyalgia controls. Methods: The Canadian consensus criteria were used for ME/CFS diagnosis, and American College of Rheumatology criteria for fibromyalgia diagnosis. Factors such as cognitive failure, depression, anxiety, and sleep disturbances were assessed by patient reported questionnaires. Clinical factors such as BVAS, vasculitis damage index, CRP and BMI were also collected. Findings: Our AAV cohort comprised 52 patients, with a mean age of 44.7 (20-79), 57% (30/52) of the patients were female. We found 51.9% (27/52) of patients fulfilled the diagnostic criteria for ME/CFS, with 37% (10/27) of those having comorbid fibromyalgia. Rates of fatigue were higher in MPO-ANCA patients, than in PR3-ANCA patients, and their symptoms were more similar to the fibromyalgia controls. Fatigue in PR3-ANCA patients was related to inflammatory markers. These differences may be due to the varied pathophysiology of the PR3- and MPO-ANCA serotypes. Interpretation: A large proportion of AAV patients suffer from debilitating fatigue consequential enough to meet the diagnostic criteria for ME/CFS. Fatigue associations were not the same between PR3- and MPO-ANCA patients, suggesting that the underlying mechanisms may be different. Future studies should consider ANCA serotype, as further research may inform different clinical treatment strategies for AAV patients suffering from ME/CFS. Funding: This manuscript was funded by the Dutch Kidney Foundation (17PhD01).