2002 General Immune System Function
In lupus there appears to be a failure of normal processes for ridding the body of auto-reactive—self-recognizing and self-destructive—lymphocytes. Removal of activated lymphocytes as an infection is cleared and deletion of auto-reactive immune system cells is achieved by triggering a biochemical suicide program, called apoptosis, in the cells.
Inherited abnormalities of the apoptosis pathway have been found in several mouse strains that develop lupus, but abnormalities in this pathway in immune system cells from lupus patients have not been consistently found.
In lymphocytes from people with lupus, Dr. Wu has found an alteration in the molecular instructions for production of a key protein in triggering apoptosis, a change that may prevent the suicide of auto-reactive lymphocytes.
With his LRI grant, Dr. Wu aimed to establish the potential role of the aberrant form of a cell-death causing receptor (Fas) in lupus.
By pinpointing a critical defect in the control of immune system cells in lupus in this way, he hoped to provide a target not only for improved diagnosis and prognosis of the disease, but also for the development of new treatments.
“Our data strongly suggest that Fas mRNA editing may play important roles in the pathogeneses of autoimmune diseases. They suggest that the level of edited Fas products could be used as disease markers for SLE.” – Dr. Wu, 2004
Although he received no separate ongoing funding since having completed the LRI grant, Dr. Wu and a colleague have has been able to continue this work as part of the large, centrally funded lupus research group that he works in.
“We really appreciate the support from LRI,” said Dr. Wu in 2010.
Rev. July 2010