Chronic Fatigue Mechanisms in Autoimmune Diseases: Lessons from Primary Biliary Cholangitis and Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) is an autoimmune disease affecting the body's connective tissues, resulting in progressive fibrosis and vasculopathy. In some cases, individuals with SSc may also develop primary biliary cholangitis (PBC), another autoimmune disease characterized by damage to their liver’s bile ducts. Chronic fatigue frequently affects SSc and PBC patients, significantly impacting their cognitive abilities and quality of life. To date, there are no reliable treatments for these patients’ fatigue. Research on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - a type of chronic fatigue characterized by post-exertional malaise - has uncovered potential connections between chronic fatigue and abnormalities in the metabolic dysfunction, atypical hypoxia responses, problems with oxygen delivery, and the immune system. The shared disease characteristics among PBC, SSc, and ME/CFS patients suggest that chronic fatigue has a physical basis and is not just a psychological phenomenon. This thesis provides an overview of the roles of metabolic dysfunctions, hypoxia responses, oxygen delivery problems, and immune system abnormalities in PBC and SSc individuals, as well as the similarities to findings in those with ME/CFS. A deeper understanding of the commonalities between SSc and PBC will serve as a catalyst for designing more effective therapies for chronic fatigue, ultimately enhancing the patients' quality of life.