title: Profile of upregulated inflammatory proteins in sera of Myasthenia Gravis patients.
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.
authors.affiliation: Uppsala University, Department of Neuroscience, Clinical Neurophysiology, BMC, Husargatan 3, 75237 Uppsala, Sweden.
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Molin
authors.affiliation: Uppsala University, Department of Neuroscience, Clinical Neurophysiology, BMC, Husargatan 3, 75237 Uppsala, Sweden.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Westerberg
authors.affiliation: Uppsala University, Department of Neuroscience, Clinical Neurophysiology, BMC, Husargatan 3, 75237 Uppsala, Sweden.
authors.forename: Anna Rostedt
authors.initials: AR
authors.lastname: Punga
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000276:immunology*; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000097:blood*; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000175:diagnosis / Q000276:immunology*; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000276:immunology; D000067616:S100A12 Protein / Q000097:blood*; D016211:Transforming Growth Factor alpha / Q000097:blood*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D018836:Inflammation Mediators; D011950:Receptors, Cholinergic; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D016211:Transforming Growth Factor alpha; D053506:Matrix Metalloproteinase 10