Researchers Identify Potential Cause of Lupus

A group of researchers at the Feinstein Institute for Medical Research has identified a protein called Blimp-1 as a likely primary cause of the adverse reaction of the immune system in lupus patients.

Common signs and symptoms of systemic lupus erythematosus, the most common type of lupus. Image credit: Mikael Haggstrom.

Common signs and symptoms of systemic lupus erythematosus, the most common type of lupus. Image credit: Mikael Haggstrom.

Lupus is an autoimmune disease that causes the immune system to lose the ability to differentiate between foreign agents and healthy tissue.

It becomes hyperactive and attacks healthy tissue, causing inflammation and damage to joints, skin, and internal organs.

According to the Lupus Foundation of America, an estimated 1.5 million Americans, and at least 5 million people worldwide, have a form of lupus.

Lupus strikes mostly women of childbearing age. However, men, children, and teenagers develop the disease, too. Most people with lupus develop the disease between the ages of 15-44.

Previous studies have shown that a polymorphism or variation in the gene PRDM1 is a risk factor for lupus.

In the new study, Feinstein Institute for Medical Research Professor Betty Diamond and co-authors were looking to examine how Blimp-1, a protein that in humans is encoded by the PRDM1 gene, regulates the immune system.

“A healthy immune system is able to identify organisms that are not normally in the body and activate cells like T-cells to attack them,” Professor Diamond said.

“In the case of patients with an autoimmune disease like lupus, the immune system has started to identify healthy cells as something to target.”

“Our study found that a low level of or no Blimp-1 in a particular cell type led to an increase in the protein cathepsin S (CTSS) which caused the immune system to identify healthy cells as something to attack — particularly in females.”

In an animal model, the researchers were able to show that females with reduced production of Blimp-1 caused an increase in CTSS, a protein that helps the immune system see microorganisms that cause disease.

This resulted in an immune system which attacked healthy cells. Male animals with the reduced production of Blimp-1 showed no change in their immune system.

Though more research is required to confirm that the risk gene PRDM1 could lead to a hyperactive immune system in human females, this is a significant discovery for better understanding the causes and potential treatments for lupus.

The findings were published online July 10, 2017 in the journal Nature Immunology.

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Sun Jung Kim et al. Increased cathepsin S in Prdm1?/? dendritic cells alters the TFH cell repertoire and contributes to lupus. Nature Immunology, published online July 10, 2017; doi: 10.1038/ni.3793

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