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Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes

Baekkeskov, S ; Landin, M LU ; Kristensen, J K ; Srikanta, S ; Bruining, G J ; Mandrup-Poulsen, T ; de Beaufort, C ; Soeldner, J S ; Eisenbarth, G and Lindgren, F , et al. (1987) In Journal of Clinical Investigation 79(3). p.34-926
Abstract

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM... (More)

Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM.

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type
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publication status
published
keywords
Adolescent, Adult, Autoantibodies/immunology, Autoantigens/immunology, Cytoplasm/immunology, Diabetes Mellitus, Type 1/genetics, Female, Humans, Immunosorbent Techniques, Islets of Langerhans/immunology, Lupus Erythematosus, Systemic/immunology, Male, Membrane Proteins/immunology, Middle Aged, Molecular Weight, Prospective Studies, Thyroid Diseases/immunology
in
Journal of Clinical Investigation
volume
79
issue
3
pages
34 - 926
publisher
The American Society for Clinical Investigation
external identifiers
  • scopus:0023090843
  • pmid:3546382
ISSN
0021-9738
DOI
10.1172/JCI112903
language
English
LU publication?
yes
id
366fb20e-1e1d-4e95-b91a-f7350d6d1b0e
date added to LUP
2021-09-17 15:58:02
date last changed
2024-04-20 13:37:25
@article{366fb20e-1e1d-4e95-b91a-f7350d6d1b0e,
  abstract     = {{<p>Antibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients are directed to a human islet cell protein of relative molecular mass (Mr) 64,000. Since IDDM seems to develop after a prodromal period of beta-cell autoimmunity, this study has examined whether 64,000 Mr antibodies could be detected in 14 individuals who subsequently developed IDDM and five first degree relatives who have indications of altered beta-cell function. Sera were screened by immunoprecipitation on total detergent lysates of human islets and positive sera retested on membrane protein preparations. Antibodies to the 64,000 Mr membrane protein were consistently detected in 11/14 IDDM patients, and in all 5 first degree relatives. 10 IDDM patients were already positive in the first samples, obtained 4-91 mo before the clinical onset of IDDM, whereas 1 patient progressed to a high 64,000 Mr immunoreactivity, at a time where a commencement of a decline in beta-cell function was detected. 64,000 Mr antibodies were detected before islet cell cytoplasmic antibodies (ICCA) in two patients. In the control groups of 21 healthy individuals, 36 patients with diseases of the thyroid and 5 SLE patients, the 64,000 Mr antibodies were detected in only one individual, who was a healthy sibling to an IDDM patient. These results suggest that antibodies against the Mr 64,000 human islet protein are an early marker of beta-cell autoimmunity and may be useful to predict a later development of IDDM.</p>}},
  author       = {{Baekkeskov, S and Landin, M and Kristensen, J K and Srikanta, S and Bruining, G J and Mandrup-Poulsen, T and de Beaufort, C and Soeldner, J S and Eisenbarth, G and Lindgren, F and Sundquist, Göran and Lernmark, Ake}},
  issn         = {{0021-9738}},
  keywords     = {{Adolescent; Adult; Autoantibodies/immunology; Autoantigens/immunology; Cytoplasm/immunology; Diabetes Mellitus, Type 1/genetics; Female; Humans; Immunosorbent Techniques; Islets of Langerhans/immunology; Lupus Erythematosus, Systemic/immunology; Male; Membrane Proteins/immunology; Middle Aged; Molecular Weight; Prospective Studies; Thyroid Diseases/immunology}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{34--926}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{Journal of Clinical Investigation}},
  title        = {{Antibodies to a 64,000 Mr human islet cell antigen precede the clinical onset of insulin-dependent diabetes}},
  url          = {{http://dx.doi.org/10.1172/JCI112903}},
  doi          = {{10.1172/JCI112903}},
  volume       = {{79}},
  year         = {{1987}},
}