Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome.

Abstract

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.

• Authors: Xiao-Li Wang, Tian-You Ling, M Cristine Charlesworth, Juan J Figueroa, Phillip Low, Win-Kuang Shen, Hon-Chi Lee
• Journal: Translational research : the journal of laboratory and clinical medicine (Transl Res) Vol. 162 Issue 1 Pg. 34-44 (Jul 2013) ISSN: 1878-1810 [Electronic] United States
• PMID: 23562385 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Mosby, Inc. All rights reserved.

Chemical References

• Immunoglobulin G

Topics

• Adolescent
• Adult
• Autoimmunity
• Chromatography, Liquid
• Electrophoresis, Gel, Two-Dimensional
• Female
• Humans
• Immunoblotting
• Immunoglobulin G (blood, immunology)
• Male
• Mass Spectrometry
• Membrane Microdomains (immunology)
• Middle Aged
• Myocardium (immunology)
• Postural Orthostatic Tachycardia Syndrome (immunology)