Abstract

The Clinical Resources Core will identify and characterize human subjects for participation in the program project. We have several large on-going clinical studies for the ascertainment of pre-diabetic individuals, as well as a large specialty clinic for the recruitment of new-onset diabetics and their family members. The purpose of this core is to direct some of the efforts of these ongoing clinical studies for the specific recruitment of individuals appropriate to this study. By building on the strengths of pre-existing clinical registries and assay development we are able to accomplish a very efficient recruitment of suitable individuals at rather low cost, and propose this as a core function jointly directed by Dr. David McCulloch at Virginia Mason Medical Center and Dr. Bill Hagopian at the University of Washington School of Medicine. We conservatively estimate identifying at least 12 pre-diabetic individuals who will progress to clinical IDDM in the course of this project and at least an equal number of clinical non-progressors who carry the pre-diabetic markers. The third set of individuals to be studied will be an age- and sex-matched control group who carry the IDDM- associated DQ alleles, but are otherwise negative for pre-diabetic phenotypes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
5P01DK049841-02
Application #
5210932
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

LaGasse, James M; Brantley, Michael S; Leech, Nicola J et al. (2002) Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies: an 8-year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care 25:505-11
Nepom, G T; Lippolis, J D; White, F M et al. (2001) Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65). Proc Natl Acad Sci U S A 98:1763-8
Ettinger, R A; Liu, A W; Nepom, G T et al. (2000) Beta 57-Asp plays an essential role in the unique SDS stability of HLA-DQA1*0102/DQB1*0602 alpha beta protein dimer, the class II MHC allele associated with protection from insulin-dependent diabetes mellitus. J Immunol 165:3232-8
Kwok, W W; Liu, A W; Novak, E J et al. (2000) HLA-DQ tetramers identify epitope-specific T cells in peripheral blood of herpes simplex virus type 2-infected individuals: direct detection of immunodominant antigen-responsive cells. J Immunol 164:4244-9
McFarland, B J; Sant, A J; Lybrand, T P et al. (1999) Ovalbumin(323-339) peptide binds to the major histocompatibility complex class II I-A(d) protein using two functionally distinct registers. Biochemistry 38:16663-70
Reichstetter, S; Kwok, W W; Nepom, G T (1999) Impaired binding of a DQ2 and DQ8-binding HSV VP16 peptide to a DQA1*0501/DQB1*0302 trans class II heterodimer. Tissue Antigens 53:101-5
Huang, S C; Glas, A M; Pinchuk, G V et al. (1999) Human B cells accumulate immunoglobulin V gene somatic mutations in a cell contact-dependent manner in cultures supported by activated T cells but not in cultures supported by CD40 ligand. Clin Exp Immunol 116:441-8
Reijonen, H; Elliott, J F; van Endert, P et al. (1999) Differential presentation of glutamic acid decarboxylase 65 (GAD65) T cell epitopes among HLA-DRB1*0401-positive individuals. J Immunol 163:1674-81
Reichstetter, S; Kwok, W W; Kochik, S et al. (1999) MHC-peptide ligand interactions establish a functional threshold for antigen-specific T cell recognition. Hum Immunol 60:608-18
Blum, J S; Ma, C; Kovats, S (1997) Antigen-presenting cells and the selection of immunodominant epitopes. Crit Rev Immunol 17:411-7

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