Leading the way to a cure


Analysis And Treatment Of Organ Damage In A Humanized Mouse Model Of Lupus

Mayadas, Tanya, PhD

Brigham and Women's Hospital, Inc.

Systemic lupus erythematosus (SLE) is a chronic, inflammatory autoimmune disorder that affects multiple organs and is associated with abnormalities at all levels of the immune system. Neutrophils, which are white blood cells that are important for defense against infections, can inflict tissue injury in lupus. 

Recently, researchers discovered variations of genes important in the activation of white blood cells that may increase susceptibility to developing lupus. Some, including those that code for receptors that bind antibodies, FcγRIIA, FcγRIIIB, and the integrin Mac-1 (ITGAM), are present on neutrophils. The overall objective of this grant is to decipher how these receptors may contribute to organ damage in lupus. 

Dr. Mayadas and her team established a model of lupus nephritis (kidney disease) that develops after blood from lupus patients is transferred into genetically engineered mice that express the uniquely human FcγRIIA and FcγRIIIB proteins on neutrophils. 

With this grant, they plan to:

• Determine how neutrophils induce organ damage after antibodies in blood serum from lupus patients are transferred into mice

• Identify compounds that inhibit FcγRIIA and determine if they can prevent organ damage in the mice that receive lupus blood serum

What this study means for people with lupus: These experiments may lead to a better understanding of the causes of lupus-related organ damage. In the future, this could lead to therapies designed to interrupt the molecular cascade responsible for this damage.

1.5 million

people in the U.S. have Lupus.

172 million

dollars committed to lupus research by the Lupus Research Alliance.

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