Abstract
This study describes specific patterns of elevated inflammatory proteins in clinical subtypes of myasthenia gravis (MG) patients. MG is a chronic, autoimmune neuromuscular disease with antibodies most commonly targeting the acetylcholine receptors (AChRab), which causes fluctuating skeletal muscle fatigue. MG pathophysiology includes a strong component of inflammation, and a large proportion of patients with early onset MG additionally present thymus hyperplasia. Due to the fluctuating nature and heterogeneity of the disease, there is a great need for objective biomarkers as well as novel potential inflammatory targets. We examined the sera of 45 MG patients (40 AChRab seropositive and 5 AChRab seronegative), investigating 92 proteins associated with inflammation. Eleven of the analysed proteins were significantly elevated compared to healthy controls, out of which the three most significant were: matrix metalloproteinase 10 (MMP-10; p = 0.0004), transforming growth factor alpha (TGF-α; p = 0.0017) and extracellular newly identified receptor for advanced glycation end-products binding protein (EN-RAGE) (also known as protein S100-A12; p = 0.0054). Further, levels of MMP-10, C-X-C motif ligand 1 (CXCL1) and brain derived neurotrophic factor (BDNF) differed between early and late onset MG. These novel targets provide valuable additional insight into the systemic inflammatory response in MG.
Highlights
Myasthenia gravis (MG) is a chronic autoimmune disease, which is caused by antibodies against receptors at the neuromuscular junction
Three samples (2 HC and 1 patient) were excluded due to unacceptable technical variations and the final cohort consisted of 87 subjects, 44 myasthenia gravis (MG) patients (23 women) and 43 healthy controls (23 women)
The cohort included 22 EOMG and 22 LOMG patients and overall median Myasthenia Gravis Foundation of America (MGFA) disease severity classification was mild MG (MGFA class II; Table 1). 39 patients had verified AChR antibodies whereas the remaining 5 patients were seronegative for AChR and MuSK antibodies. 18 patients had undergone thymectomy and 16 patients had current treatment with immunosuppressive medication
Summary
Myasthenia gravis (MG) is a chronic autoimmune disease, which is caused by antibodies against receptors at the neuromuscular junction. There are no circulating serum biomarkers that correlate with the disease state between patients or different MG subtypes[9]. MicroRNA (miRNA) have been described as potential biomarkers regarding miR-150-5p and miR-21-5p for AChR +MG10,11 and the let[7] family for MuSK +patients[12]. Both miR150-5p and miR-21-5p are involved in the regulation of the autoimmune response, and in particular the development of T- and B-cells. No previous study has focused on defining a broad inflammatory circulating protein profile in MG patients and in different clinical MG subtypes. We analysed protein expressions within the clinical subgroups EOMG vs. LOMG, immunosuppressive medication, gender and thymectomy
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