Specific Cellular Interactions Can Be Blocked in Lupus
(BlackDoctor.org) — Researchers have found a way to reduce disease activity
in people with lupus nephritis by blocking contact between lymphocytes.
nephritis is a form of kidney inflammation that can lead to kidney failure. The
researchers were able to relieve symptoms in some study participants and send
the lupus nephritis into remission in others who received longer courses of
treatment. Lupus, also called systemic lupus erythematosus or SLE, is an
autoimmune disease in which the B lymphocytes, white blood cells that secrete
antibodies, are hyperactive and target healthy tissues by mistake.
The findings, featured on the cover of the November 15 issue of the Journal
of Clinical Investigation, offer hope that the autoimmune reactions of lupus may
one day be prevented. The work was conducted by Amrie Grammer, Ph.D., Peter
Lipsky, M.D., and Gabor Illei, M.D., of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases (NIAMS), as well as other researchers at the
National Institutes of Health (NIH) and other institutions.
Previous laboratory experiments showed it was possible to interrupt the
interactions between cells that cause an autoimmune reaction. The investigators
wanted to find out whether they could reproduce those results in lupus patients.
They recruited six volunteers with lupus nephritis. These volunteers had
previously participated in NIAMS clinical trials studying the natural history of
lupus nephritis with standard treatment. Investigators treated the volunteers
with an antibody that was created to interfere with cell interactions,
specifically, interactions between one protein, CD40, and another, CD154. The
antibody, developed in mice, was humanized; that is, it was designed to mimic
human antibodies so that the volunteers’ immune systems wouldn’t attack it and
render it useless.
To find out if the interactions had been blocked successfully, the
investigators conducted extensive tests of B lymphocytes in the participants’
blood before and after treatment. The researchers observed a significant
decrease in the activity of B lymphocytes and the number of antibody-secreting
plasma cells, both of which indicate disease activity in lupus, after treatment.
Also, the volunteers experienced relief of symptoms.
The trial was stopped when some of the participants developed blood clots,
which may be related to underlying vascular disease in certain patients. Dr.
Lipsky states, “This trial was conducted using a small number of patients. We’ll
need to do larger, comprehensively controlled clinical trials to determine a
safe and effective means to block these vascular side effects.”