Document Detail


T-cell reactivity to 38 kD insulin-secretory-granule protein in patients with recent-onset type 1 diabetes.
MedLine Citation:
PMID:  1675318     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Type 1 diabetes seems to be an autoimmune disease in which T cells have a substantial role. A possible target antigen was suggested by the proliferation of CD4 T cells from a newly diagnosed patient in response to a 38 kD polypeptide of the insulin-secretory-granule membrane. To see whether this reactivity is widespread at disease onset, we have generated T-cell lines in vitro from peripheral blood mononuclear cells of nineteen children of caucasoid origin with newly diagnosed type 1 diabetes and sixteen healthy controls matched for age and HLA antigens. The procedure involved two cycles of incubation with a rat beta-cell tumour subcellular fraction enriched in secretory granules and plasma membrane components, followed by a proliferation assay. Fourteen (74% [95% confidence interval 49-91%]) of the patients' cell lines showed a positive proliferative response on subsequent exposure to the islet-cell antigen preparation compared with only two (13% [2-38%]) of the controls (p = 3 x 10(-4); difference 61% [44-87%]). Two subjects who had high titres of islet-cell autoantibodies (ICA) without clinical diabetes produced responsive T-cell lines. Reactivity towards the 38 kD fraction of insulin-secretory-granule membranes was found only in patients (eight of ten responders tested; 95% CI 44-98%) and one ICA-positive non-diabetic subject. Detection of an ongoing autoimmune T-cell response might be useful diagnostically and could lead to prevention of diabetes through specific immunotherapy.
Authors:
B O Roep; A A Kallan; W L Hazenbos; G J Bruining; E M Bailyes; S D Arden; J C Hutton; R R de Vries
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  337     ISSN:  0140-6736     ISO Abbreviation:  Lancet     Publication Date:  1991 Jun 
Date Detail:
Created Date:  1991-07-17     Completed Date:  1991-07-17     Revised Date:  2009-09-29    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1439-41     Citation Subset:  AIM; IM    
Affiliation:
Department of Immunohaematology and Blood Bank, University Hospital Leiden, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Autoantibodies / analysis
Autoantigens / administration & dosage*,  chemistry,  pharmacology
CD4-Positive T-Lymphocytes / drug effects*
Cells, Cultured
Child
Diabetes Mellitus, Type 1 / immunology*,  metabolism
Female
Humans
Insulin / immunology*
Islets of Langerhans / immunology
Leukocytes, Mononuclear / immunology
Lymphocyte Activation / drug effects,  immunology
Male
Membrane Proteins / chemistry,  pharmacology*
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Autoantigens; 0/Membrane Proteins; 0/islet cell antibody; 11061-68-0/Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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