Specific Cellular Interactions Can Be Blocked in Lupus

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    (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.”

    The idea to interrupt these cell interactions occurred to the investigators
    eight years ago while doing laboratory research. At that time, Drs. Grammer and
    Lipsky determined that B lymphocytes express the CD40-ligand molecule, also
    called CD154. This ligand attaches to a certain protein on another cell, which
    is called the cell-surface receptor CD40. A ligand on one cell and a receptor on
    another will fit together, or bind, like a lock and key. Once CD154 (ligand)
    binds CD40 (receptor) on another cell, the interaction signals the body to make
    antibodies that bind invading organisms and ultimately destroy them. In lupus
    patients, the B lymphocytes are hyperactive, creating antibodies that bind
    healthy cells by mistake and thereby destroy healthy tissues. Dr. Grammer says,
    “These clinical findings are consistent with the published preclinical
    laboratory studies and suggest that CD154-CD40 interactions are a central target
    of therapy in SLE.”

    Stephen I. Katz, M.D., Ph.D., director of the NIAMS, says, “This is exactly
    what translational research is all about, taking what we learn in our labs and
    translating it into treatments which benefit people with diseases. I look
    forward to hearing much more about their progress.”

    Lupus is often called an antibody-mediated disease, which means it occurs
    when the body makes antibodies towards itself. It can affect many parts of the
    body, including the joints, skin, kidneys, heart, lungs, blood vessels and
    brain. Some of the most common lupus symptoms include extreme fatigue, painful
    or swollen joints (arthritis), unexplained fever, skin rashes and kidney
    problems. Many more women than men have lupus. It is three times more common in
    African American women than in Caucasian women, and it is also more common in
    women of Hispanic, Asian and Native American descent.

    NIAMS is a part of the Department of Health and Human Services’ NIH. For more
    information about NIAMS, call the information clearinghouse at (301) 495-4484 or
    (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.


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