Mechanism behind autoimmune disorder revealed

February 7, 2018 by Will Doss, Northwestern University
Plasma cells showing accumulation (green) of antibody within cells (red). Credit: Northwestern University

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 . 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, also a member of the Robert H. Lurie Comprehensive Cancer Center.

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.

"Our data demonstrate that this creates an opportunity for anti-PE antibodies that are brought into the cells to bind to the PE in these tiny vesicles and attack the cells from within — a miniature 'Trojan Horse' process," Zhao said. "This causes chaos within the cell, sending it into an inflammatory state, leading to a greater risk of and pregnancy complications."

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.

These novel discoveries shed light on how cellular vulnerability to aPE is mediated and explain some of its clinical symptoms, according to the study. Because endosomes are an integral part of nearly every type of cell, linking the activity of aPE to clinical symptoms will be a priority for scientists in future investigations, Zhao said.

Explore further: Scientists find key to miscarriages in blood clotting disorder

More information: Songwang Hou et al. Early endosome as a pathogenic target for antiphosphatidylethanolamine antibodies, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1714027115

Related Stories

Scientists find key to miscarriages in blood clotting disorder

November 28, 2017
Monash University researchers have potentially shed light on why women with the rare autoimmune disorder Antiphospholipid syndrome (APS) are prone to successive pregnancy losses.

Team engineers anti-inflammatory antibodies that may treat autoimmune disease

December 21, 2017
A team of Massachusetts General Hospital (MGH) investigators has found a way to engineer antibodies within an organism, converting autoantibodies that attack "self" tissues into anti-inflammatory antibodies in animal models ...

Cancer immunotherapy may work in unexpected way

May 18, 2017
Antibodies to the proteins PD-1 and PD-L1 have been shown to fight cancer by unleashing the body's T cells, a type of immune cell. Now, researchers at the Stanford University School of Medicine have shown that the therapy ...

Preventing autoimmune disease after a viral infection

October 2, 2017
The key weapon against viruses and bacteria that invade the body is production of antibodies, which act like guided missiles to attack and neutralize pathogens.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

Recommended for you

A synthetic approach to helping the immune system thwart infections

February 22, 2018
Yale researchers have developed a set of synthetic molecules that may help boost the strength of a key, virus-fighting protein.

Scientists find molecular link between Vitamin A derivative and mouse intestinal health

February 22, 2018
New research shows that all-trans-retinoic acid (atRA), the active form of vitamin A, regulates immune system responses in the mouse intestine by controlling expression of the protein HIC1 in cells known as innate lymphoid ...

Animal study shows how to retrain the immune system to ease food allergies

February 21, 2018
Treating food allergies might be a simple matter of teaching the immune system a new trick, researchers at Duke Health have found.

'Icebreaker' protein opens genome for T cell development, researchers find

February 20, 2018
Almost all cells in the human body have identical DNA sequences, yet there are 200-plus cell types with different sizes, shapes, and chemical compositions. Determining what parts of the genome are read to make protein and ...

Preventive treatment for peanut allergies succeeds in study

February 20, 2018
The first treatment to help prevent serious allergic reactions to peanuts may be on the way. A company said Tuesday that its daily capsules of peanut powder helped children build tolerance in a major study.

Infection site affects how a virus spreads through the body

February 20, 2018
A person is more likely to get infected by HIV through anal intercourse than vaginal, but no one knows quite why. A new study by scientists at the Gladstone Institutes shows that infection sites could affect the immune system's ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.