Insulin-dependent diabetes mellitus-specific chimeric polypeptid

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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536 232, C07H 2104

Patent

active

060605936

ABSTRACT:
The present invention provides a chimeric polypeptide comprising an epitope of GAD65 protein and a structural region comprising a polypeptide of the GAD family, wherein the chimeric polypeptide is a more specific diagnostic for insulin dependent diabetes mellitus than intact GAD65 and produces fewer false positives than intact GAD65. The invention further provides a method of screening a subject for risk of developing IDDM, comprising contacting the chimeric polypeptide of claim 1 with a biological sample containing antibodies from the subject and detecting binding between an antibody in the biological sample and the chimeric polypeptide, the detection of binding indicating the subject is at risk of developing IDDM.

REFERENCES:
patent: 5200318 (1993-04-01), Rabin et al.
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Noriko Ujihara, Kendra Daw, Roberto Gianani, Esper Boel, Liping Yu, and Alvin C. Powers: Identification of Glutamic Acid Decarboxylase Autoantibody Heterogeneity and Epitope Regions in Type I Diabetes, Diabetes, 43:968-975 (Aug. 1994).
Wiltrud Richter, Yuguang Shi and Steinunn Baekkeskov: Autoreactive Epitopes Defined by Diabetes-Associated Human Monoclonal Antibodies . . . , Proc. Natl. Acad. Sci. USA 90:2832-2836 (Apr. 1993).
Wiltrud Richter, Josef Endl, Thomas H. Eiermann, Michael Brandt, Rosemarie Kientsch-Engel, Charles Thivolet, Herbert Jungfer and Werner A. Scherbaum: Human Monoclonal Islet Cell Antibodies From a Patient With Insulin-Dependent Diabetes Mellitus Reveal Glutamate Decarboxylase as the Target Antigen, Proc. Natl. Acad. Sci. USA 89:8467-8471 (Sep. 1992).
Kendra Daw, Noriko Ujihara, Mark Atkinson, and Alvin C. Powers: Glutamic Acid Decarboxylase Autoantibodies in Stiff-Man Syndrome and Insulin=Dependent Diabetes Mellitus Exhibit Similarities and Differences in Epitope Recognition, The Journal of Immunology 156(2):818-25 (1996).
Kendra Daw and Alvin C. Powers: Two Distinct Glutamic Acid Decarboxylase Auto-Antibody Specificities in IDDM Target Different Epitopes, Diabetes 44(2):216-20 (Feb. 1995).
Michele Solimena, Ronald Dirkx, Jr., Michal Radzynski, Olaf Mundigi, and Pietro De Camilli: A Signal Located Within Amino Acids 1-27 of GAD65 is Required for Its Targeting to the Golgi Complex Region, The Journal of Cell Biology 126(2):331-341 (Jul. 1994).

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