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Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):13798-13803. doi: 10.1073/pnas.1714027115. Epub 2017 Dec 11.

Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies.

Author information

1
Feinberg Cardiovascular Research Institute, Department of Medicine, Northwestern University, Chicago, IL 60611.
2
Department of Cell and Molecular Biology, Northwestern University, Chicago, IL 60611.
3
Allergy-Immunology Division, Department of Medicine, Northwestern University, Chicago, IL 60611.
4
Rheumatology Division, Department of Medicine, Northwestern University, Chicago, IL 60611.
5
Feinberg Cardiovascular Research Institute, Department of Medicine, Northwestern University, Chicago, IL 60611; m-zhao@northwestern.edu.

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.

KEYWORDS:

antiphosphatidylethanolamine; antiphospholipid syndromes; duramycin; early endosome; phosphatidylethanolamine

PMID:
29229837
PMCID:
PMC5748199
DOI:
10.1073/pnas.1714027115
[Indexed for MEDLINE]
Free PMC Article

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