In 2001, the LRI awarded Dr. Weigert funding to determine the genetic mechanisms controlling the appearance of DNA-specific autoantibodies in healthy people—and the reasons these mechanisms fail in people with lupus.
Dr. Weigert subsequently discovered that a large proportion of DNA-specific auto-antibodies in lupus are generated by a process known as “receptor editing.”
TNF antagonism in SLE
In this innovative study, Dr. Davidson takes on the challenge of teasing apart the complex mechanisms by which a protein (a cytokine) called “TNF-alpha” apparently protects against systemic lupus at the same time that it increases inflammation and worsens lupus kidney disease.
In lupus, immune system cells in the blood that normally fight infection somehow become abnormal and attack the body, causing often widespread tissue damage. The cells make infection-fighting molecules such as CD40L at the wrong times, for example, which in turn causes further abnormal behavior in immune system cells.
In lupus, a defect develops in the body's T cells, which are designed to attack all foreign cells. Dr. Zhang's laboratory has found that mice who produce too much of a certain inhibitory protein in T cells (c-FLIP) develop a syndrome that resembles lupus in humans. With the LRI grant, Dr.