Mechanism behind autoimmune disorder

Northwestern Medicine scientists discovered a previously-unknown mechanism of disease behind a specific autoimmune disorder. 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.

The 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.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, this causes chaos within the cell, sending it into an inflammatory state, leading to a greater risk of blood clot formation and pregnancy complications.

It's important to note the inflammatory response may be the principal effect of aPE 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 antibodies to clinical symptoms will be a priority for scientists in future investigations.
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How viruses developed immunity

 SIDT2 protein is an important factor for cells to detect viral components in their environment, and create an immune response to reduce or stop the spread of the virus.

During a viral infection, ribonucleic acid RNA a genetic material similar to DNA is released into the environment around the infected cells. SIDT2 allowed viral RNA to be shuttled between compartments within cells, allowing it to reach the proteins that trigger anti-viral immunity.

The RNA is in a 'double-stranded' form, called 'dsRNA', that is not normally found in human body. Human cells have evolved ways to detect double stranded ribonucleic acid dsRNA as a warning sign of an active viral infection and, in this way, dsRNA acts as an important trigger for cells to produce an anti-viral immune response.

Cells constantly protect their environment by swallowing small samples of their environment into compartments known as endosomes. SIDT2 was the crucial missing link needed to transport dsRNA out of endosomes, and enable activation of immune response.

Viruses have many strategies to prevent an infected cell from activating the immune system to their presence.
SIDT2 is critical for uninfected cells to detect viral RNA in their environment, this means uninfected cells can trigger protective immunity before they even encounter the virus.
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