Leading the way to a cure


The role of immune complexes and BAFF in promoting atherosclerosis in lupus

Vilen, Barbara J., PhD

The University of North Carolina at Chapel Hill

Many people with lupus develop heart disease, diabetes, and become overweight, likely because immune dysregulation affects inflammation. Are regulators of the immune system that contribute to lupus kidney disease linked to problems with regulation of cells processes that lead to atherosclerosis? Earlier studies by Dr. Vilen’s laboratory identified one (of several) pathways that leads to increased BAFF (B-cell activating factor) secretion in people with lupus. Now she hopes to identify how that pathway may lead to the development of atherosclerosis.

Lupus is associated with elevated levels of BAFF. Dr. Vilen’s laboratory recently found that one of several sources of BAFF is produced when apoptotic debris fails to be degraded and as a consequence is recycled by the cell back to the cell. The recycling in this context is for the un-degraded immune complex to be sent from inside the cell back to the cell surface. This process might lead to chronic activation of the receptors bound by the apoptotic debris, perhaps leading to heightened BAFF production by the cell in the case of FcgRs.

It is possible that over extended periods of time, elevated BAFF activates PI3K/mTOR, which leads to fat cells (adipocytes) being activated and matured, encouraging inflammation. Using mice lacking a part of the immune system, she and her team will seek to determine whether increasing levels of BAFF in the presence of mTOR encourages the production of fatty substances, leading to atherosclerosis. Also, the researchers will use gene neutralization, blocking or deletion to investigate the roles of the BAFF receptor BR3, mTOR, and FcgR1. 

What this study means for people with lupus: This research has the potential to advance researchers’ understanding of how and why people with lupus develop heart (cardiovascular) disease. The research has the potential to identify targets for effective therapies. 

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