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UCSF Finds Potential New Antibody Treatment for Autoimmune Diseases
Date:1/22/2009

tial new approach to developing safer, more targeted therapies based on human antibodies."

Therapies using proper doses of these newly discovered antibodies may carry less risk of infections or tumors than current treatments, since the antibodies target T cells' specific patrolling activities, rather than their overall function.

Goetzl's team evaluated a woman with a low number of blood T cells and frequent infections in the ears, urinary tract and lungs. The infection of several organs suggested a defect in the patient's immune system similar to Acquired Immune Deficiency Syndrome (AIDS), but the patient tested negative for human immunodeficiency virus (HIV).

Further studies revealed that the patient's CD4 T cells did not move out of her lymph nodes as they would in a normal immune system because her body created antibodies to one type of sphingosine 1-phosphate (S1P) receptor. S1P is critical to appropriate immune responses since it regulates T- and B-cell movement throughout the body by interacting with its receptor. The patient's antibodies blocked the signaling that triggers T-cell movement from the thymus and lymph nodes into blood and then into many organs.

Researchers then explored whether the woman's antibodies effectively could inhibit an autoimmune response in mice. Antibodies against the S1P receptor, created from the patient's antibody-producing cells, were injected into mice that were induced to develop colitis. The result was a significant reduction in severity of their diseases, including colitis-associated weight loss, in those mice compared to mice that did not receive the antibodies.

"These results have broad biological implications, since the cells that carry out our immune responses are present in every organ," said Goetzl, director of UCSF Allergy and Immunology Research, which focuses on developing new diagnostic approaches and treatments for allergic and immunological diseases. <
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