Auto antibodies present at onset of type i diabetes recognize multiple islet cell antigens

D. G. Karounos, L. J. Nell, J. W. Thomas

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Antibodies to islet antigens are useful markers of the pathological process that results in destruction of beta cells in type I diabetes. The targets of these antibodies, however, are not well characterized and their role in the pathological process remains to be established. To better understand the range of antigens recognized by autoantibodies in type I diabetes mellitus, we carried out immunoblotting on protein extracts from human islets and rat insulinomas. Using this approach high titer antibodies specific for islet antigens were detected in 20/28 sera from recent onset type I diabetics and were infrequent (4/28) in sera from age-matched controls. Sera from diabetics reacted with multiple antigens at titers from 1/100-1/4000 while control sera usually bound a single band at lower dilutions. Although antigens of M, 52, 84, 116 and 150 kilodalton were recognized most frequently, no antigen was bound by more than 50% of diabetic sera. Some of these antigens enriched in the membrane fraction while others were not. The data demonstrate that a heterogeneous group of islet antigens is recognized by autoantibodies present at the onset of type I diabetes when islet destruction is complete. These findings contrast previous reports using immunoprecipi-tation with undiluted sera that principally identify a 64 kDa islet antigen. Thus, the immunoblot technique detects a different set of reactivities than previously identified by immunoprecipitation. The pattern of multiple reactivities with both surface and cytoplasmic antigens suggest that many autoantibodies may be generated by beta cell destruction and some of these may amplify the ongoing immune response.

Original languageEnglish
Pages (from-to)79-91
Number of pages13
JournalAutoimmunity
Volume6
Issue number1-2
DOIs
StatePublished - 1990

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute of Health RR0035021S1, DK36189, and l-P30-AM-27685-01Al to the Diabetes and Endocrinology Research Center, Baylor College of Medicine. We thank Drs. A.E. Boyd, B.S. Dunbar, and D.M. Marcus for helpful discussions. The help of Drs D.G. Rogers and R.N. Marshall, Jr. in obtaining serum samples is greatly appreciated. We thank Drs. D.W. Scharp and P.E. Lacy, Diabetes and Endocrinology Research Center, St. Louis, for providing the isolated human islets.

Funding

This work was supported by grants from the National Institute of Health RR0035021S1, DK36189, and l-P30-AM-27685-01Al to the Diabetes and Endocrinology Research Center, Baylor College of Medicine. We thank Drs. A.E. Boyd, B.S. Dunbar, and D.M. Marcus for helpful discussions. The help of Drs D.G. Rogers and R.N. Marshall, Jr. in obtaining serum samples is greatly appreciated. We thank Drs. D.W. Scharp and P.E. Lacy, Diabetes and Endocrinology Research Center, St. Louis, for providing the isolated human islets.

FundersFunder number
Diabetes and Endocrinology Research Center
National Institutes of Health (NIH)RR0035021S1
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK036189
Baylor College of Medicine

    Keywords

    • Immunoblot
    • Islet cell antibodies
    • Type I diabetes

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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