Mechanism behind autoimmune disorder revealed

Northwestern Medicine scientists discovered a previously-unknown mechanism of disease behind a specific autoimmune disorder, findings published in the Proceedings of the National Academy of Sciences.

The scientists observed antibodies that targeted phosphatidylethanolamine, an important phosopholipid, from within the endosomes of cells. This discovery was the first observation of a pathogenic mechanism behind anti-phosphatidylethanolamine (aPE) autoimmunity, an immune system disorder that's been correlated with thrombosis, transplant failure and pregnancy loss.


It was first reported decades ago, but exactly how aPE autoimmunity worked had remained a mystery despite a large body of literature documenting its prevalence, according to Ming Zhao, PhD, associate professor of Medicine in the Division of Cardiology and senior author on the paper.

Autoimmune diseases usually develop when antibodies—proteins which neutralize pathogens—erroneously attack cells while circulating through the bloodstream. To target those cells, the antibodies bind to accessible antigen targets on the exterior surface of cells, but Zhao and other investigators had been unable to identify an accessible target for aPE—until now.

"The discovery was made somewhat by chance—we left a binding study overnight and discovered, to our surprise, that the antigen is accessible after antibodies are internalized into cells," said Zhao.

That internalization happens through the endosome, a part of the cell that samples the external environment and gathers in signaling molecules. In this case, the endosome also draws in the antibodies, making the cells vulnerable.

It's important to note the inflammatory response may be the principal effect of aPE, according to Zhao, because it means anti-inflammatory treatment is likely to be more effective than anti-coagulants.

GLOSSARY:
phosopholipid - a lipid containing a phosphate group in its molecule
endosomes - membrane-delimited intracellular transport carriers.
thrombosis - clotting of the blood in a part of the circulatory system.
antibodies - blood proteins produced in response to and counteracting a specific antigen.
antigen - a toxin or other foreign substance which induces an immune response in the body.

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