Article
Autoantibodies targeting muscarinic acetylcholine receptors: implications on fatigue in systemic sclerosis
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Published: | September 4, 2017 |
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Background: Muscarinic acetylcholine receptors (mAChR) are neuroimmune G protein-coupled receptors comprising 5 subtypes (M1-M5). Autoantibodies recognizing mAChRs have been linked to chronic fatigue syndrome. Fatigue is common in patients with autoimmune diseases such as systemic sclerosis (SSc) and is frequently ranked as one of the most wearing symptoms.
Methods: In a first study, we analyzed autoantibodies targeting M1-M5 in 113 SSc patients and 113 sex- and age-matched healthy controls by ELISA. In an ongoing second study we apply self-report questionnaires to investigate frequency and severity of fatigue (brief fatigue inventory, multidimensional fatigue inventory, fatigue severity scale), depression (patient health questionnaire-9), pain (numerical rating scales), sleepiness (epworth sleepiness scale), sleep quality (pittsburgh sleep quality index) and chronotype (munich chronotype questionnaire) in relation to anti-M1-M5 autoantibodies in 100 SSc patients.
Results: In the first study we found significantly decreased levels of autoantibodies targeting M2, M4 and M5 in SSc patients compared to healthy controls. In the second study, 72 SSc patients have completed the questionnaires until now. 24% of these patients suffered from severe fatigue and 49% felt unusually fatigued during the last week. 33% showed at least mild depression, 59% enhanced sleepiness and 63% poor sleep quality. Fatigue correlated with depression (r=0.673, P<0.0001), sleepiness (r=0.591, P<0.0001), sleep quality (r=0.272, P=0.0261) and pain (r=0.556, P<0.001). Data on chronotype and autoantibodies are currently under analysis.
Conclusion: Our findings demonstrate a high frequency of fatigue, depression, sleepiness and poor sleep in SSc patients. Altered patterns of autoantibodies targeting mAChR may contribute to the pathogenesis of fatigue in SSc and potentially offer new therapeutic possibilities.