University of California

Other

Yale University

Steinunn Baekkeskov

Henk-Jan Aanstoot

Wiltrud Richter

Mark Namchuk

John Kim

Yuguang Shi

Michele Solimena

Franco Folli

Pietro Decamilli

Sang-Mo Kang

Andries Erik Braat

Peter G Stock

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

Assays for identifying human patients at risk for developing insulin-dependent diabetes mellitus rely on detection of autoantibodies to a 38 kD autoantigen present in pancreatic &#x3b2;-cells in patient sera. It has been found that autoantibodies to this particular autoantigen developed in patients well before clinical onset of the disease in a significant subpopulation of prediabetic patients. Useful assays will frequently combine detection of autoantibodies to the 38 kD autoantigen with detection of other known markers of IDDM, such as autoantibodies to a 64 kD autoantigen (glutamic acid decarboxylase).

Methods for diabetes susceptibility assessment in asymptomatic patients

This invention generally provides polypeptides comprising a noncleavable form of a Fas ligand and having a capacity to activate a Fas receptor-mediated pathway involved in cell death, pharmaceutical compositions of such polypeptides, nucleic acids encoding such polypeptides, and cell lines capable of expressing these nucleic acids. Also provided are therapeutic and prophylactic methods of using such polypeptides, compositions, and cells lines for treating patients suffering from disorders resulting from dysregulation or inappropriate stimulation of the Fas receptor-mediated pathway.

Noncleavable Fas ligand

Assays for identifying human patients at risk for developing insulin-dependent diabetes mellitus rely on detection of autoantibodies to a 38 kD autoantigen present in pancreatic &bgr;-cells in patient sera. It has been found that autoantibodies to this particular autoantigen developed in patients well before clinical onset of the disease in a significant subpopulation of prediabetic patients. Useful assays will frequently combine detection of autoantibodies to the 38 kD autoantigen with detection of other known markers of IDDM, such as autoantibodies to a 64 kD autoantigen (glutamic acid decarboxylase).

The invention provides fragments of GAD.sub.65 that are specifically reactive with at least one class of GAD.sub.65 autoantibody. Most fragments are substantially free of N-terminal amino acids that would otherwise limit solubility. Different fragment contain epitopes for different classes of GAD.sub.65 autoantibodies. The fragments are used in methods of diagnosing and treating insulin dependent diabetes mellitus and stiff man syndrome.

Reagents and methods for the diagnosis and treatment of diabetes and

Assays for identifying human patients at risk for developing insulin-dependent diabetes mellitus rely on detection of autoantibodies to a 38 kD autoantigen present in pancreatic .beta.-cells in patient sera. It has been found that autoantibodies to this particular autoantigen developed in patients well before clinical onset of the disease in a significant subpopulation of prediabetic patients. Useful assays will frequently combine detection of autoantibodies to the 38 kD autoantigen with detection of other known markers of IDDM, such as autoantibodies to a 64 kD autoantigen (glutamic acid decarboxylase).

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.

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San Francisco, CA, United States of America

Steinunn Baekkeskov