title: The serum of dysautonomia patients enhances proliferation and signaling in Schwann cells.
abstract: Disorders of the autonomic nervous system, or dysautonomias, affect a large segment of the population, especially women, and represent a diagnostic challenge. Identification of biomarkers for autonomic disorders, and the subsequent development of screening methods, would benefit diagnosis and symptom management. We studied the effect of sera from fifteen well-characterized dysautonomia patients (mean age 49+/-16 years, 10 females, 5 males) and ten control subjects (mean age 31+/-14 years, 5 females, 5 males) on the proliferation of cultured Schwann cells and activity of mitogen-activated protein kinases (MAPKs) in these cells. We correlated characteristics of patients with the effects on cell proliferation and signaling. Overall, we observed a significant increase in proliferation when Schwann cells were incubated with sera from female dysautonomia patients when compared to control subjects and male patients. Interestingly, removal of IgGs significantly reduced the proliferative effect of patient sera. We also observed significant activation of p38 MAPK following incubation with both male and female patient sera. These results suggest that patient sera contain factors that contribute to aberrant Schwann cell proliferation and signaling and may ultimately lead to autonomic nerve dysfunction. Our observations represent a promising first step in the identification of dysautonomia biomarkers.
authors.affiliation: Department of Pathology, Case Western Reserve University School of Medicine, 2103 Cornell Road, Cleveland, OH 44016-7288, USA.
authors.forename: Rein H
authors.initials: RH
authors.lastname: Lambrecht
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Pollard
authors.forename: Amer
authors.initials: A
authors.lastname: Alshekhlee
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chelimsky
authors.forename: Liliana N
authors.initials: LN
authors.lastname: Berti-Mattera
mesh_terms: D000328:Adult; D000368:Aged; D001685:Biological Factors / Q000097:blood*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D054969:Primary Dysautonomias / Q000097:blood*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000201:enzymology*; D044967:Serum; D012737:Sex Factors; D015398:Signal Transduction; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001685:Biological Factors; D007074:Immunoglobulin G; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases