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Inflammatory islet damage in patients bearing HLA-DR 3 and/or DR 4 haplotypes does not lead to islet autoimmunity

Summary

The hypothesis was tested that islet autoimmunity is induced by ongoing islet cell destruction in subjects with susceptibility genes HLA-DR 3 and/or DR 4. Sixty-one patients with confirmed chronic pancreatitis were analysed, 30 of whom expressed HLA-DR 3 and/or DR 4. Electron microscopy studies in 10 patients showed that the inflammatory process also affected islets, as recognisable from islet cell lysis, intrainsular fibrosis and immune cell infiltrates. None of the sera tested contained any of three markers of islet autoimmunity, ICA, IAA or GAD antibodies. A correlation was seen between the loss of exocrine function, as determined by the ALTAB-test, and of beta-cell function, as determined by the C-peptide response to i.v. glucagon. However, there was no preferential loss of beta-cell function in patients with HLA-DR 3 and/or DR 4. We conclude that islet cell destruction occurs during chronic pancreatitis, but does not trigger islet autoimmunity, even in the presence of HLA-DR 3 and/or DR 4.

Abbreviations

IDDM:

Insulin-dependent diabetes mellitus

ICA:

islet cell antibodies

IAA:

insulin autoantibodies

GAD:

glutamate decarboxylase

JDF:

Juvenile Diabetes Foundation

PAB A:

N-acetyl-L-tyrosyl-paraaminobenzoic acid

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Correspondence to E. F. Lampeter or H. Kolb or I. Seifert or D. Lohmann or J. W. Heise or J. Bertrams or M. R. Christie or V. Kolb-Bachofen.

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Lampeter, E.F., Kolb, H., Seifert, I. et al. Inflammatory islet damage in patients bearing HLA-DR 3 and/or DR 4 haplotypes does not lead to islet autoimmunity. Diabetologia 37, 471–475 (1994). https://doi.org/10.1007/s001250050134

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Key words

  • IDDM
  • chronic pancreatitis
  • islet cell antibodies, autoimmunity