Muscarinic acetylcholine receptors (mAChR) are G-protein-coupled neuroimmune receptors, highly prevalent in the nervous system and on immune cells. They have been shown to be involved in the regulation of immune function and autoantibodies directed against mAChRs are found in autoimmune diseases. Interestingly, elevated concentrations of anti-mAChRs have been demonstrated in patients with chronic fatigue syndrome. Fatigue is very common in patients with autoimmune diseases such as Systemic Sclerosis (SSc) and in addition, we found that SSc patients display altered concentrations of autoantibodies targeting mAChRs compared to healthy controls. We want to further investigate the mechanisms triggered by autoantibodies targeting muscarinic acetylcholine receptors in patients with SSc and their correlation with fatigue and the clinical spectrum of SSc.