Interferon Gamma Seen in Study to Be a Lupus Trigger, and a Potential Treatment Target

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by Chris Comish |

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Systemic lupus erythematosus

Interferon gamma could be a key trigger for lupus, a finding that may provide information leading to new treatments for the autoimmune disease, according to researchers at Penn State College of Medicine. The study, “IFN-γ receptor and STAT1 signaling in B cells are central to spontaneous germinal center formation and autoimmunity,” appeared in the Journal of Experimental Medicine.

Systemic lupus erythematosus (often simply called lupus) is a disease in which the body’s own immune system attacks several organs, with the kidneys accounting for the most affected organ. Lupus is about nine times more common in women than in men, and can flare unexpectedly, leading to frequent and costly medical problems. Understanding how immune system molecules may contribute to lupus is an important area of research.

Previous research demonstrated that in people and experimental animals with lupus, immune system cells known as B lymphocytes produce antibodies that inappropriately attack the body, even when there is no infection. This autoimmune response contributes to the disease.

Interferon gamma could be a critical trigger of the autoimmune response.

Investigators led by Ziaur S.M. Rahman, an assistant professor of microbiology and immunology, focused on the immune system molecule interferon gamma to understand its possible role in lupus.  They studied mice with an experimental form of lupus, whose interferon gamma receptors had been removed from their B cells.

Compared to mice that retained B-cell interferon gamma receptors, the mice with no receptors had less autoimmune tissue damage and lower levels of autoantibodies, appearing to have reduced lupus symptoms.

“This suggests that interferon gamma signaling in B cells is critical for the formation of spontaneously-developed B lymphocyte groups and autoimmunity,” Rahman said. “If you could target this interferon gamma signaling pathway in B cells, you could potentially treat lupus.”

Researchers also found, importantly, that the mice appeared to have a normal response to actual infections.

Current treatments for lupus involve immunosuppressive drugs, but these drugs block the immune system and can cause other illnesses in people more susceptible to infection. The Penn State researchers believe that targeting interferon gamma could lead to the development of new medicines that treat lupus without causing as many side effects or associated illnesses.