Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome
Open accessAbstract
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.
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Autoantibodies targeting α1- and β-adrenergic receptors, as well as cardiac lipid raft-associated proteins, have been found in POTS patients.
“Circulating antibodies to α1-and β-adrenergic receptors and cardiac lipid raft-associated proteins have also been discovered in POTS (Fedorowski et al., 2017;Wang et al., 2013;Li et al., 2014).”
From Postural tachycardia syndrome – Diagnosis, physiology, and prognosis (2018) · cites this paper as Wang et al., 2013
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- Authors
- Wang, X.-L., Ling, T.-Y., Charlesworth, M. C., Figueroa, J. J., Low, P., Shen, W.-K., & Lee, H.-C.
- Affiliations
- Mayo Clinic (US)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Wang, Xiao-Li
- Venue
- Translational Research
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 162
- Issue
- 1
- Pages
- 34-44
- ISSN
- 1878-1810 (ISSN-L)
- 1931-5244
- PMC
- PMC3691285
- OpenAlex
- W2107485112
- Cited by
- 41
- References
- 33
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 9 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 4
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Translational research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R56HL074180, HL 74180, R01HL074180, HL080118, R01HL080118)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- postural orthostatic tachycardia syndrome, autoantibodies, caveolae, beta-adrenergic signaling, calcium signaling, oxidative phosphorylation, fatty acid metabolism, ubiquitination, autoimmunity
- MeSH terms
- Adolescent, Adult, Chromatography, Liquid, Female, Humans, Immunoglobulin G, Male, Middle Aged, Myocardium, Mass Spectrometry, Immunoblotting, Electrophoresis, Gel, Two-Dimensional, Autoimmunity, Membrane Microdomains, Postural Orthostatic Tachycardia Syndrome
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