Yale University

University of California

Michele Solimena

Steinunn Baekkeskov

Henk-Jan Aanstoot

Franco Folli

Pietro Decamilli

Ronald A Dirkx, Jr

Constance A F M Berghs

Assays for the detection of diabetes and prediabetic status rely on exposing patient serum samples to purified ligand capable of binding autoantibodies specific for a 64kD autoantigen present on pancreatic &#x3b2;-cells. The purified ligand is usually purified glutamic acid decarboxylase (GAD) or a fragment or analog thereof. Preferably, the assays will detect the presence of antibodies to both lower molecular weight GAD and higher molecular weight GAD since diabetic and prediabetic status may be associated with only one of these two forms. The assays can be performed using conventional protocols, such as radioimmunoassay, enzyme-linked immunosorbent assay, and enzyme assay. Methods for treating diabetes comprise administering pharmaceutical compositions including the purified ligand, particularly when coupled to an immunoglobulin or lymphoid cell to induce tolerance. Alternatively, tolerance may be induced by administering attenuated T-helper cells, or isolated T-cell receptors, where the T-helper cells have been isolated based on their reactivity with GAD or equivalent ligand.

Methods for the diagnosis of diabetes

The invention is directed to polypeptide or fragments thereof which interact with autoantigens of autoimmune diseases such as type I diabetes, and nucleic acid sequences which encode those polypeptide. The invention is also directed to methods for screening for autoimmune diseases such as type I diabetes, and methods and compositions for modulating hormone and neuropeptide secretion using proteins which interact with autoantigens of autoimmune diseases.

&bgr;IV-spectrin-polypeptides and nucleic acids encoding same

Assays for the detection of diabetes and prediabetic status rely on exposing patient serum samples to purified ligand capable of binding autoantibodies specific for a 64 kD autoantigen present on pancreatic .beta.-cells. The purified ligand is usually purified glutamic acid decarboxylase (GAD) or a fragment or analog thereof. Preferably, the assays will detect the presence of antibodies to both lower molecular weight GAD and higher molecular weight GAD since diabetic and prediabetic status may be associated with only one of these two forms. The assays can be performed using conventional protocols, such as radioimmunoassay, enzyme-linked immunosorbent assay, and enzyme assay. Methods for treating diabetes comprise administering pharmaceutical compositions including the purified ligand, particularly when coupled to an immunoglobulin or lymphoid cell to induce tolerance. Alternatively, tolerance may be induced by administering attenuated T-helper cells, or isolated T-cell receptors, where the T-helper cells have been isolated based on their reactivity with GAD or equivalent ligand.

Methods for the diagnosis and treatment of diabetes

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New Haven, CT, United States of America

Michele Solimena