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Early autoantibody responses in prediabetes are IgG1 dominated and suggest antigen-specific regulation.
J. Immunol. 163, 525-532 (1999)
The islet autoimmunity of preclinical type 1 diabetes remains poorly characterized in humans. In this paper, the IgG subclass response to the islet autoantigens insulin, glutamic acid decarboxylase, and IA-2 was studied sequentially from birth to diabetes onset or current follow-up in 26 autoantibody positive offspring of parents with diabetes. Islet autoantibody appearance was characterized by an early IgG1 peak response to one or more Ags, most commonly to insulin, at a median age of 2.2 yr (interquartile range, 2-2.9 yr). In five offspring, an acute fulminant beta-cell destruction and diabetes onset occurred during this initial Ab response. In the remainder, early Ab levels declined markedly, and Ab peaks against other beta cell Ags arose sequentially over several years suggesting regulation and spreading of autoimmunity. Second peak Ab responses to the same Ag were observed in only two offspring, both developing diabetes at this time. Two others developed diabetes with declining Ab levels. Abs of IgG1 subclass dominated against each Ag, and other subclasses, were usually only detected during peak IgG1 responses. The IgG4 response to insulin was exceptional, being dominant over IgG1 in four offspring and in five others appeared and/or persisted after IgG1 levels declined. These Th2-associated IgG4 responses were not correlated with protection from diabetes. The presence of IgG1-restricted responses to DA2 were associated with diabetes development. These findings suggest that type 1 diabetes has an early acute destructive phase of beta cell autoimmunity, which may be regulated and which spreads chronically until diabetes onset.
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Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Sprache
englisch
Veröffentlichungsjahr
1999
HGF-Berichtsjahr
0
ISSN (print) / ISBN
0022-1767
e-ISSN
1550-6606
Zeitschrift
Journal of Immunology
Quellenangaben
Band: 163,
Heft: 1,
Seiten: 525-532
Verlag
American Association of Immunologists
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Diabetes and Obesity (IDO)
Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)
Institute of Diabetes Research (IDF)
Institute of Pancreatic Islet Research (IPI)
POF Topic(s)
30502 - Diabetes: Pathophysiology, Prevention and Therapy
Forschungsfeld(er)
Helmholtz Diabetes Center
PSP-Element(e)
G-502290-001
PubMed ID
10384157
WOS ID
000080973700068
Erfassungsdatum
1999-07-01