American Journal of Epidemiology Vol. 136, No. 5: 503-512
Copyright © 1992 by The Johns Hopkins University School of Hygiene and Public Health
other |
Autoimmunity and Genetics Contribute to the Risk of Insulindependent Diabetes Mellitus in Families: Islet Cell Antibodies and HLA DQ Heterodimers
1Department of Epidemiology, Graduate School of Public Health University of Pittsburgh Pittsburgh, PA
2Division of Immunogenetics, Department of Pediatrics University of Pittsburgh Pittsburgh, PA
3Department of Pathology and Laboratory Medicine, University of Florida Gainesville, FL
4Department of Endocrinology, Children's Hospital of Pittsburgh Pittsburgh, PA
The risk for insulin-dependent diabetes mellitus (IDDM) associated with genetic susceptibility markers at the human leukocyte antigen (HLA) DQA1 and DQB1 loci was evaluated among individuals with and those without islet cell antibodies. A total of 108 antibody-positive parents and siblings of IDDM patients from the Pittsburgh registry were identified among 1, 592 who were screened. HLA-DQ molecular typing was performed on 79 of these individuals and on 78 antibody-negative relatives. There were similar proportions of homozygotes for both of the diabetogenic alleles DQA1 arginine-52 (R/R) and DQB1 non-asparate-57 (nD/nD) among the antibody-positive and antibody-negative relatives (19.0 and 15.4%, respectively). However, subsequent development of IDDM was restricted to individuals who were both antibody positive and carried the potential to make at least one diabetogenic DQ heterodimer. A dose-response effect was observed among the antibody-positive relatives, in which two of 18 capable of generating one diabetogenic heterodimer and six of 29 generating two heterodimers became insulin requiring. Nine of 15 who were homozygous for both R/R and nD/nD, coding exclusively for diabetogenic variants, became diabetic over the course of the follow-up. With a multivariate model, the relative risk for IDDM among those with islet cell antibodies who were also R/R and nD/nD was estimated to be 229.3 compared with those lacking both, after age and sex were controlled for. The data suggest that while autoimmunity, indicated by the presence of cytoplasmic islet cell antibodies, may be relatively common, it progresses only in those with variant HLA-DQ molecules. Am J Epidemiol 1992; 136: 503–12
allergy and immunology; autoantibodies; autoimmunity; diabetes mellitus, insulindependent; genetic markers; HLA antigens; HLA-DQ antigens; islets of Langerhans
5Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, IL
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Orilieri, G. Cappellano, R. Clementi, A. Cometa, M. Ferretti, E. Cerutti, F. Cadario, M. Martinetti, D. Larizza, V. Calcaterra, et al. Variations of the Perforin Gene in Patients With Type 1 Diabetes Diabetes, April 1, 2008; 57(4): 1078 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. S. Yap, G. Giddings, E. Pocock, and J. K. Chantler Lack of islet neogenesis plays a key role in beta-cell depletion in mice infected with a diabetogenic variant of coxsackievirus B4 J. Gen. Virol., November 1, 2003; 84(11): 3051 - 3068. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Winer, I. Astsaturov, R. Gaedigk, D. Hammond-McKibben, M. Pilon, A. Song, V. Kubiak, W. Karges, E. Arpaia, C. McKerlie, et al. ICA69null Nonobese Diabetic Mice Develop Diabetes, but Resist Disease Acceleration by Cyclophosphamide J. Immunol., January 1, 2002; 168(1): 475 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Winer, I. Astsaturov, R. K. Cheung, K. Schrade, L. Gunaratnam, D. D. Wood, M. A. Moscarello, P. O'Connor, C. McKerlie, D. J. Becker, et al. T Cells of Multiple Sclerosis Patients Target a Common Environmental Peptide that Causes Encephalitis in Mice J. Immunol., April 1, 2001; 166(7): 4751 - 4756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Winer, I. Astsaturov, R. K. Cheung, L. Gunaratnam, V. Kubiak, M. A. Cortez, M. Moscarello, P. W. O'Connor, C. McKerlie, D. J. Becker, et al. Type I Diabetes and Multiple Sclerosis Patients Target Islet Plus Central Nervous System Autoantigens; Nonimmunized Nonobese Diabetic Mice Can Develop Autoimmune Encephalitis J. Immunol., February 15, 2001; 166(4): 2831 - 2841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Becker, R. E. LaPorte, I. Libman, M. Pietropaolo, and H.-M. Dosch Prevention of Type 1 Diabetes: Is Now the Time? J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 498 - 506. [Full Text]
|
|
|
|
|
|
H.-M. Dosch, R. K. Cheung, W. Karges, M. Pietropaolo, and D. J. Becker Persistent T Cell Anergy in Human Type 1 Diabetes J. Immunol., December 15, 1999; 163(12): 6933 - 6940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Azar, H. Tamim, H. N. Beyhum, M. Z. Habbal, and W. Y. Almawi Type I (Insulin-Dependent) Diabetes Is a Th1- and Th2-Mediated Autoimmune Disease Clin. Vaccine Immunol., May 1, 1999; 6(3): 306 - 310. [Full Text] [PDF]
|
|
|
|
|
|
W. Y. Almawi, H. Tamim, and S. T. Azar T Helper Type 1 and 2 Cytokines Mediate the Onset and Progression of Type I (Insulin-Dependent) Diabetes J. Clin. Endocrinol. Metab., May 1, 1999; 84(5): 1497 - 1502. [Abstract] [Full Text]
|
|
|
|
|
|
L. Yu, K. W. Brewer, S. Gates, A. Wu, T. Wang, S. R. Babu, P. A. Gottlieb, B. M. Freed, J. Noble, H. A. Erlich, et al. DRB104 and DQ Alleles: Expression of 21-Hydroxylase Autoantibodies and Risk of Progression to Addison's Disease J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 328 - 335. [Abstract] [Full Text]
|
|