HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, L. Articles by Krischer, J. P. Search for Related Content PubMed PubMed Citation Articles by Yu, L. Articles by Krischer, J. P. Social Bookmarking                What's this?

Expression of GAD65 and Islet Cell Antibody (ICA512) Autoantibodies Among Cytoplasmic ICA+ Relatives Is Associated With Eligibility for the Diabetes Prevention Trial-Type 1

¹ Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, Colorado
² H. Lee Moffitt Cancer Research Center, University of South Florida, Tampa, Florida
³ Juvenile Diabetes Program, Weill Medical College, Cornell University, New York, New York
⁴ Joslin Diabetes Center, Harvard University, Boston, Massachusetts
⁵ Seattle Veterans Affairs Medical Center, University of Washington, Seattle, Washington

More than 71,000 relatives of type 1 diabetic patients have been screened for cytoplasmic islet cell antibodies (ICAs), GAD65 autoantibodies (GAAs), and ICA512 autoantibodies (ICA512AAs). Among those 71,148 relatives, 2,448 were cytoplasmic ICA+, and the remainder were ICA-. Of the ICA+ group, 1,229 (50.2%) were positive for GAAs and/or ICA512AAs. Among ICA- relatives, 1,897 (2.76%) were positive for GAAs and/or ICA512AAs. Given the large number of relatives positive for cytoplasmic ICA and negative for "biochemically" determined autoantibodies, and the converse, we analyzed the proportion of ICA+ relatives found eligible to participate in the intervention phase of Diabetes Prevention Trial-Type 1 (DPT-1). To be eligible for the parenteral insulin DPT-1 trial, a relative had to have first-phase insulin secretion below the 1st percentile of cut-points (for parents) or below the 10th percentile (for siblings and offspring). To be eligible for the oral insulin trial, a relative had to have first-phase insulin secretion above cut-points (>1st percentile for parents, >10th percentile for siblings/offspring) and be positive for anti-insulin autoantibodies. For both trials, DQB1*0602 was an exclusion criteria, cytoplasmic ICA positivity had to be confirmed, and an oral glucose tolerance test had to result in nondiabetic levels. Of 572 relatives found to be eligible for trial entry, 442 (77.3%) were positive for GAAs and/or ICA512AAs, although overall only 50.2% of ICA+ relatives were positive for GAAs and/or ICA512AAs. The positive predictive value for trial eligibility for ICA+ relatives with GAAs or ICA512AAs who completed staging was 51.0%. In contrast, only 11.9% of ICA+ but GAA- and ICA512AA- relatives were found to be eligible by DPT criteria for trial entry. Positivity for biochemically determined autoantibodies among cytoplasmic antibody–positive relatives is associated with eligibility for the DPT-1 study.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				V. Seyfert-Margolis, T. D. Gisler, A. L. Asare, R. S. Wang, H. M. Dosch, B. Brooks-Worrell, G. S. Eisenbarth, J. P. Palmer, C. J. Greenbaum, S. E. Gitelman, et al. Analysis of T-Cell Assays to Measure Autoimmune Responses in Subjects With Type 1 Diabetes: Results of a Blinded Controlled Study Diabetes, September 1, 2006; 55(9): 2588 - 2594. [Abstract] [Full Text] [PDF]

				A. Quinn, M. McInerney, D. Huffman, B. McInerney, S. Mayo, K. Haskins, and E. Sercarz T cells to a dominant epitope of GAD65 express a public CDR3 motif Int. Immunol., June 1, 2006; 18(6): 967 - 979. [Abstract] [Full Text] [PDF]

				M. J. Redondo, S. Babu, A. Zeidler, T. Orban, L. Yu, C. Greenbaum, J. P. Palmer, D. Cuthbertson, G. S. Eisenbarth, J. P. Krischer, et al. Specific Human Leukocyte Antigen DQ Influence on Expression of Antiislet Autoantibodies and Progression to Type 1 Diabetes J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1705 - 1713. [Abstract] [Full Text] [PDF]

				J. M. Barker, K. J. Barriga, L. Yu, D. Miao, H. A. Erlich, J. M. Norris, G. S. Eisenbarth, and M. Rewers Prediction of Autoantibody Positivity and Progression to Type 1 Diabetes: Diabetes Autoimmunity Study in the Young (DAISY) J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3896 - 3902. [Abstract] [Full Text] [PDF]

				J. P. Krischer, D. D. Cuthbertson, and C. Greenbaum Male Sex Increases the Risk of Autoimmunity but not Type 1 Diabetes Diabetes Care, August 1, 2004; 27(8): 1985 - 1990. [Abstract] [Full Text] [PDF]

				A. REWERS, S. BABU, T. B. WANG, T. L. BUGAWAN, K. BARRIGA, G. S. EISENBARTH, and H. A. ERLICH Ethnic Differences in the Associations between the HLA-DRB1*04 Subtypes and Type 1 Diabetes Ann. N.Y. Acad. Sci., November 1, 2003; 1005(1): 301 - 309. [Abstract] [Full Text] [PDF]

				D. G. SILVA, B. CHARLTON, W. COWDEN, and N. PETROVSKY Prevention of Autoimmune Diabetes through Immunostimulation with Q Fever Complement-Fixing Antigen Ann. N.Y. Acad. Sci., November 1, 2003; 1005(1): 423 - 430. [Abstract] [Full Text] [PDF]

				J. P. Krischer, D. D. Cuthbertson, L. Yu, T. Orban, N. Maclaren, R. Jackson, W. E. Winter, D. A. Schatz, J. P. Palmer, and G. S. Eisenbarth Screening Strategies for the Identification of Multiple Antibody-Positive Relatives of Individuals with Type 1 Diabetes J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 103 - 108. [Abstract] [Full Text] [PDF]