University of Florida Research Foundation Inc

Other

The United States of America As Represented by the Department of Health

Research Corporation Technologies, Inc.

Noel K Maclaren

Mark A Atkinson

Michael S Lan

Abner L Notkins

Yao-Huo Song

Yao H Song

Qing Li

Andrew Muir

The method and compositions of this invention provide an effective and reliable substitute for the currently employed ICA assay for diabetes. By providing a method for detecting autoantibodies to both GAD and IA-2 auto-antigens, the method provides a chemical assay which has improved reliability. In addition, these antigens may be employed in therapeutic regimens aimed at achieving immune tolerance and therefore amelioration of the clinical condition.

Materials and methods for detection of insulin dependent diabetes

The subject invention concerns a novel process for the early detection of insulin dependent diabetes (IDD). The novel process described here enables the detection of the onset of IDD before clinical symptoms appear. The novel process involves the detection, in a sample of biological fluid, of an autoantibody which is highly specific to individuals who will later develop the clinical manifestations of IDD. Novel treatments for the prevention of IDD are also described.

Methods and compositions for early detection and treatment of insulin dependent diabetes mellitus

Disclosed are novel autoantigens and methods useful in the detection of autoantibodies in persons that have developed, or are at risk of developing, autoimmune hypoparathyroidism. The novel autoantigens of the subject invention may be used to achieve early diagnosis and treatmcnt of autoimmune hypoparathyroidism, and possibly other autoimmune diseases which arc frequently associated with autoimmune hypoparathyroidism.

Parathyroid cytosolic autoantigens recognized by autoantibodies from

Compositions and methods for the treatment or prevention of insulin dependent diabetes (IDD) are provided. Specifically, glutamic acid decarboxylase (GAD) proteins, and fragments. thereof, can be administered to an animal in order to the reduce the severity of IDD.

Method and compositions for early detection and treatment of insulin

The method and compositions of this invention provide an effective and reliable substitute for the currently employed ICA assay for diabetes. By providing a method for detecting autoantibodies to GAD.sub.65, IA-2 and a previously unidentified antigen termed IA-2.beta. herein, the method provides a chemical assay which has improved reliability. In addition, these antigens may be employed in therapeutic regimens aimed at achieving amelioration of the clinical condition.

Materials and methods for detection and treatment of insulin-dependent

The subject invention concerns compositions and methods useful for the prevention or amelioration of autoimmune diseases. Specifically exemplified are compositions and methods useful in immunizing to prevent insulin dependent diabetes. In a preferred embodiment, diabetes is prevented by the parenteral administration of a composition comprising specific antigenic peptides of insulin and further comprising incomplete Fruend's adjuvant.

Methods and compositions for delaying or preventing the onset of

The invention pertains to the discovery of antigenic cross reactivity between a pancreatic 64K autoantigen and glutamic acid decarboxylase (GAD). Autoantibodies toward GAD were found to be associated with insulin dependent diabetes (IDD). More specifically, the invention pertains to the use of GAD for the diagnosis, prevention and treatment of insulin dependent diabetes (IDD).

Methods and compositions for the early detection and treatment of

Acquired hypoparathyroidism (AH) occurs frequently as a component of type I autoimmune polyglandular disease (APS-I) or as a sporadic isolated disease in adults. Whereas autoantibodies to the parathyroid glands have been reported in AH, their very existence remains controversial. We report here the detection of autoantibodies as identified through immunoblotting using sera from AH patients. The antibodies were specific to parathyroid autoantigens obtained through differential centrifugation of fresh human hypercellular parathyroid glands, obtained shortly after their surgical removal for tertiary hyperparathyroidism in patients with renal failure. Autoantibodies were detected against several parathyroid specific proteins in the 17 AH sera tested. Twelve (70%) reacted to a protein of 70 kDa, while 16 (94%) reacted to a protein of 80 kDa, and 3 (18%) reacted to a protein of 120-140 kDa, respectively. The 70 and 80 kDa proteins were localized to the cytosolic fraction of the parathyroid extract, and the 120-140 kDa protein to the membrane fraction. The autoantibodies were also detectable using a dog parathyroid gland as an antigen source. However, they could not be identified using cultured human melanocytes or in rat pituitary cells as antigen sources. Sera from 50 patients with various other autoimmune diseases as well as 22 normal controls were also tested, and none reacted with any of the above specific parathyroid proteins. It is concluded that autoantibodies to 3 major autoantigens in the human parathyroid gland extract have been detected in AH patients. Furthermore, our data indicates that the 120-140 kDa autoantigen is the calcium sensing receptor and that the reactive epitope largely resides in its extracellular domain. These data confirm the autoimmune nature of AH, and the invention provides a method for detecting AH or propensity for AH as well as a method for treating AH.

Autoantibodies in patients with acquired hypoparathyroidism and assay

The subject invention concerns a process for the early detection of insulin dependent diabetes (IDD). The process described here enables the detection of the onset of IDD before clinical symptoms appear. The process involves the detection, in a sample of biological fluid, of an autoantibody which is highly specific to individuals who will later develop the clinical manifestations of IDD. Novel treatments for the prevention of IDD are also described.

An epitope of 21-hydroxylase has been identified which specifically reacts with autoantibodies to 21-hydroxylase. This epitope immunoreacts with anti-adrenocortical autoantibodies characteristically present in patients having autoimmune Addison's disease. The peptide can be used in a specific, sensitive immunoassay for the detection of these autoantibodies in the diagnosis of Addison's disease. The immunoassay permits the diagnosis of autoimmune Addison's disease and has considerable value in the screening of persons at risk. Persons in the early phases or at clinical onset of any kind of adrenocortical disease can also be screened to exclude Addison's disease as a cause.

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Archer, FL, United States of America

Noel K Maclaren