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Ras Signal Defect in SLE May Offer Target
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.
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.
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.
Ankylosing Spondylitis: Risk for Renal Stones
CHICAGO — Renal stones are more prevalent in ankylosing spondylitis patients than in those with rheumatoid arthritis, according to the results of a preliminary study presented at the combined annual meeting of the Central Society for Clinical Research and the Midwestern section of the American Federation for Medical Research.
The investigation, led by Susan A. Leonard, M.D., of the University of Minnesota, Minneapolis, was the first to describe an association between nephrolithiasis and spondyloarthritis since a Croatian study that was published more than 30 years ago (Reumatizam 1973;20:106–10), according to Hollis E. Krug, M.D., who presented the latest data in a poster session at the meeting.
In their retrospective cohort study of 44 patients with spondyloarthritis and 51 controls with RA undergoing treatment at the Minneapolis Veterans Affairs Medical Center, the Minnesota-based researchers found a statistically significant greater prevalence of renal calculi in patients with ankylosing spondylitis compared with those with RA (38.6% versus 15.7%).
“There didn't seem to be a higher rate of coexistent disease in spondyloarthritis patients that could increase the risk for renal stones,” Dr. Krug said. However, medication use at diagnosis of nephrolithiasis was not documented in the patients' charts, and that may have played a role in formation of kidney stones, she told this newspaper.
The Minneapolis group plans to study more patients in an attempt to explain the reason for this association.
CHICAGO — Renal stones are more prevalent in ankylosing spondylitis patients than in those with rheumatoid arthritis, according to the results of a preliminary study presented at the combined annual meeting of the Central Society for Clinical Research and the Midwestern section of the American Federation for Medical Research.
The investigation, led by Susan A. Leonard, M.D., of the University of Minnesota, Minneapolis, was the first to describe an association between nephrolithiasis and spondyloarthritis since a Croatian study that was published more than 30 years ago (Reumatizam 1973;20:106–10), according to Hollis E. Krug, M.D., who presented the latest data in a poster session at the meeting.
In their retrospective cohort study of 44 patients with spondyloarthritis and 51 controls with RA undergoing treatment at the Minneapolis Veterans Affairs Medical Center, the Minnesota-based researchers found a statistically significant greater prevalence of renal calculi in patients with ankylosing spondylitis compared with those with RA (38.6% versus 15.7%).
“There didn't seem to be a higher rate of coexistent disease in spondyloarthritis patients that could increase the risk for renal stones,” Dr. Krug said. However, medication use at diagnosis of nephrolithiasis was not documented in the patients' charts, and that may have played a role in formation of kidney stones, she told this newspaper.
The Minneapolis group plans to study more patients in an attempt to explain the reason for this association.
CHICAGO — Renal stones are more prevalent in ankylosing spondylitis patients than in those with rheumatoid arthritis, according to the results of a preliminary study presented at the combined annual meeting of the Central Society for Clinical Research and the Midwestern section of the American Federation for Medical Research.
The investigation, led by Susan A. Leonard, M.D., of the University of Minnesota, Minneapolis, was the first to describe an association between nephrolithiasis and spondyloarthritis since a Croatian study that was published more than 30 years ago (Reumatizam 1973;20:106–10), according to Hollis E. Krug, M.D., who presented the latest data in a poster session at the meeting.
In their retrospective cohort study of 44 patients with spondyloarthritis and 51 controls with RA undergoing treatment at the Minneapolis Veterans Affairs Medical Center, the Minnesota-based researchers found a statistically significant greater prevalence of renal calculi in patients with ankylosing spondylitis compared with those with RA (38.6% versus 15.7%).
“There didn't seem to be a higher rate of coexistent disease in spondyloarthritis patients that could increase the risk for renal stones,” Dr. Krug said. However, medication use at diagnosis of nephrolithiasis was not documented in the patients' charts, and that may have played a role in formation of kidney stones, she told this newspaper.
The Minneapolis group plans to study more patients in an attempt to explain the reason for this association.