Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies

Songwang Hou, Heike Fölsch, Ke Ke, Joan Cook Mills, Rosalind Ramsey-Goldman, Ming Zhao*

*Corresponding author for this work

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Phosphatidylethanolamine (PE) is a major phospholipid species with important roles in membrane trafficking and reorganization. Accumulating clinical data indicate that the presence of circulating antibodies against PE is positively correlated with the symptoms of antiphospholipid syndromes (APS), including thrombosis and repeated pregnancy loss. However, PE is generally sequestered inside a normal resting cell, and the mechanism by which circulating anti-PE antibodies access cellular PE remains unknown. The studies presented here were conducted with synthetic PE-binding agents, plasma samples from patients with anti-PE autoimmunity, and purified anti-PE antibodies. The results suggest that the cellular vulnerability to anti-PE antibodies may be mediated by the binding of PE molecules in the membrane of the early endosome. Endosomal PE binding led to functional changes in endothelial cells, including declines in proliferation and increases in the production of reactive oxygen species, as well as the expression of inflammatory molecules. Collectively, our findings provide insight into the etiology of anti-PE autoimmunity and, because endosomes are of central importance in almost all types of cells, could have important implications for a wide range of biological processes.

Original languageEnglish (US)
Pages (from-to)13798-13803
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number52
DOIs
StatePublished - Dec 26 2017

Keywords

  • Antiphosphatidylethanolamine
  • Antiphospholipid syndromes
  • Duramycin
  • Early endosome
  • Phosphatidylethanolamine

ASJC Scopus subject areas

  • General

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