CHICAGO — An apparent defect in Ras signaling in lupus patients' T cells contributes to sustained expression of CD40 ligand and may provide a target to suppress disease activity, Dilrukshie Cooray, M.D., reported at the combined annual meeting of the Central Society for Clinical Research and the Midwestern section of the American Federation for Medical Research.
Previous evidence suggested that a defect in the downregulation of the Ras pathway in lupus T cells led to the failure to develop anergy and to an abnormally prolonged expression of CD40 ligand (CD40L) (Arthritis Rheum. 2001;44:397–407).
Working on that hypothesis, Dr. Cooray and colleagues performed immunocytochemistry to test freshly isolated lymphocytes from patients with SLE and healthy controls before and after inactivation of Ras with the Ras inhibitor S-farnesylthiosalicylic acid.
They found that Ras inactivation markedly decreased the level of CD40L in T cells obtained from patients with lupus but not from healthy subjects.
“Our preliminary results support the hypothesis that there is an intrinsic defect in Ras signaling in lupus patients' T cells that contributes to sustained expression of CD40L,” reported Dr. Cooray of the rheumatology department at Loma Linda (Calif.) University. “By suppressing levels of CD40L, we think we are able to suppress disease activity.”
Because the researchers tested only six patients, it's not clear what level of CD40L is necessary for suppression of disease activity.