The Autoimmune Response in Scleroderma

A Key Discovery

The key discovery of Dr. Antony Rosen and colleagues in his lab at Johns Hopkins University is related to the autoimmune response in scleroderma, which is highly disease-specific and targets a unique group of self molecules. In normal individuals, the immune system does not respond to these host molecules, but is directed instead against foreign molecules encoded by bacteria or viruses. Rosen’s team focused on understanding why individuals with scleroderma generate an immune response against these specific self-molecules. Through this investigation, they developed critical insights into the process that initiates this devastating disease.

The investigators identified a novel cell death pathway in scleroderma tissue, which changes the structure of these self molecules, so that they look different to the immune system. The cells of the immune system recognize these altered forms of the molecules as foreign, and make an immune response against self. Significantly, it was not previously understood that this central process plays a role in human autoimmune disease, and therefore has important implications for many autoimmune diseases in addition to scleroderma.

Dr. Rosen’s laboratory is now working to define why this pathway becomes unusually active in scleroderma and whether the pathway is active both at the beginning and in the later stages of the disease. Studies to identify natural and pharmacological inhibitors of the pathway are also under way and may provide a unique approach to prevent and treat this disease.

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