Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome. Transl Res 2013 Jul;162(1):34-44
Date
04/09/2013Pubmed ID
23562385Pubmed Central ID
PMC3691285DOI
10.1016/j.trsl.2013.03.002Scopus ID
2-s2.0-84879418981 (requires institutional sign-in at Scopus site) 29 CitationsAbstract
Lipid rafts are specialized plasma membrane microdomains that serve as platforms for integrating cellular signal transductions. We have recently reported that autoantibodies against cardiac membrane proteins are present in patients with postural orthostatic tachycardia syndrome (POTS). In this study, we examined the presence of autoimmunoreactive IgGs against lipid raft proteins in these patients. IgGs were purified from the sera of 10 patients and 7 normal controls. Cardiac lipid raft preparations were isolated from normal human heart tissue. The lipid raft-associated proteins were resolved by 2-dimensional gel electrophoresis and immunoblotted against IgGs from each subject. Protein spots that reacted specifically with patient IgGs were identified by nano-liquid chromatography-mass spectrometry/mass spectrometry. Thirty-four such protein spots, and 72 unique proteins were identified. The targets of autoimmunoreactive IgGs include proteins associated with caveolae structure, adrenergic signaling, calcium signaling, cytostructures, chaperone and energy metabolism. Multiple pathways were involved including those that regulate caveolae-mediated signaling, oxidative phosphorylation, fatty acid metabolism, protein ubiquitination, and cardiac β-adrenergic signaling. Our results suggest that cardiac lipid raft-associated proteins are targets of autoimmunoreactive IgGs from patients with POTS. Autoimmunity may play a role in the pathogenesis of POTS.
Author List
Wang XL, Ling TY, Charlesworth MC, Figueroa JJ, Low P, Shen WK, Lee HCAuthor
Juan Jose Figueroa MD Assistant Professor in the Neurology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Autoimmunity
Chromatography, Liquid
Electrophoresis, Gel, Two-Dimensional
Female
Humans
Immunoblotting
Immunoglobulin G
Male
Mass Spectrometry
Membrane Microdomains
Middle Aged
Myocardium
Postural Orthostatic Tachycardia Syndrome
