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Research Article Free access | 10.1172/JCI116574

Islet cell autoantigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen.

M Pietropaolo, L Castaño, S Babu, R Buelow, Y L Kuo, S Martin, A Martin, A C Powers, M Prochazka, and J Naggert

Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Barbara Davis Center for Childhood Diabetes, University of Colorado Health Science Center, Denver 80262.

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Published July 1, 1993 - More info

Published in Volume 92, Issue 1 on July 1, 1993
J Clin Invest. 1993;92(1):359–371. https://doi.org/10.1172/JCI116574.
© 1993 The American Society for Clinical Investigation
Published July 1, 1993 - Version history
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Abstract

We have identified a novel 69-kD peptide autoantigen (ICA69) associated with insulin-dependent diabetes mellitus (IDDM) by screening a human islet lambda gt11 cDNA expression library with cytoplasmic islet cell antibody positive sera from relatives of IDDM patients who progressed to the overt disease. The deduced open reading frame of the ICA69 cDNA predicts a 483-amino acid protein. ICA69 shows no nucleotide or amino acid sequence relation to any known sequence in GenBank, except for two short regions of similarity with BSA. The ICA69 cDNA probe hybridizes with a 2-kb mRNA in poly(A+) RNA from human pancreas, brain, heart, thyroid, and kidney, but not with skeletal muscle, placenta, spleen, or ovary. Expression of ICA69 was also detected in beta cells and cell lines, as well as in tumoral tissue of islet cell origin. The native ICA69 molecule migrates to 69 kD in SDS-PAGE as detected with specific antibodies. Serum samples from relatives of IDDM patients specifically reacted with affinity-purified recombinant ICA69 on Western blotting. The structural gene for ICA69 was designated ICA1. A homologue in the mouse, designated Ica-1 was mapped to the proximal end of chromosome 6 (within 6 cM of the Met protooncogene). ICA69 adds a novel autoantigen to the family of identified islet target molecules, and by the manner of its identification and characterization large amounts of antigen are available for development of quantitative, convenient predictive assays for autoantibodies and analysis of the role of this molecule in diabetes autoimmunity, as well as its physiologic function.

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