2003 Abstracts

 

Late-onset autoimmune diabetes in relatives of people with type 1 diabetes

Fourlanos S Colman PG, Harrison LC

Ann NY Acad Sci 1005:370-373 (2003)

The Melbourne Prediabetes Family Study, a prospective study of first-degree relatives of people with type 1 diabetes (T1D), provided an opportunity to examine late-onset autoimmune diabetes within the context of a family history of T1D. We compared genetic, immunologic, and clinical features in relatives of people with T1D, who developed early- versus late-onset diabetes.

[Visit article page on Ann NY Acad Sci website]

 

Guidelines for intervention trials in subjects with newly-diagnosed type 1 diabetes

Greenbaum CJ, Harrison LC

Diabetes 52:1059-1065 (2003)

Type 1, or insulin-dependent diabetes, is an autoimmune disease that culminates in the destruction of insulin-producing ß-cells in the islets of the pancreas. Studies in the nonobese diabetic (NOD) mouse model of spontaneous type 1 diabetes provide "proof-of-concept" that the disease is preventable. People with type 1 diabetes and their relatives, researchers, government, and industry are eager to move forward and test candidate intervention/prevention therapies in humans. Such therapies may entail risks, including accelerated loss of ß-cell function, malignancy, and infection. Scientifically and ethically, investigators are obliged to maximize the information gained from intervention trials and minimize risks. One way of achieving this is by standardizing trial protocols. Standardization of islet autoantibody assays and of the intravenous glucose tolerance test for measuring first-phase insulin response has been a major advance, allowing stratification for disease risk among relatives. The literature on intervention trials in newly diagnosed type 1 diabetic patients reveals that entry criteria, trial design and duration, and outcome measures differ considerably. Adoption of standardized protocols would permit comparative and pooled data analysis and facilitate evaluation of potential therapies.
Our purpose here is to highlight issues pertaining to trial variables and suggest ways of standardizing protocols for phase I and II intervention trials in newly diagnosed patients. These issues will be discussed under three major headings: trial subjects, trial design, and trial outcome measures.

[View free full-text article at Diabetes website]

 

Antigen-induced regulatory T cells in autoimmunity

Von Herrath MG, Harrison LC

Nat Rev Immunol 3:223-232

The ultimate goal of any treatment for autoimmune diseases is antigen- and/or site-specific suppression of pathology. Autoaggressive lymphocytes need to be eliminated or controlled to prevent tissue damage and halt the progression of clinical disease. Strong evidence is emerging that the induction of regulatory T (T(Reg)) cells by autoantigens can suppress disease, even if the primary, initiating autoantigens are unknown and if inflammation is progressive. An advantage of these autoreactive T(Reg) cells is their ability to act as bystander suppressors and dampen inflammation in a site-specific manner in response to cognate antigen expressed locally by affected tissues. In this review, we consider the nature and function of such antigen-specific T(Reg) cells, and strategies for their therapeutic induction are discussed.

[Visit article page on Nat Rev Immunol website]

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