INFLAMMATORY ISLET DAMAGE IN PATIENTS BEARING HLA-DR 3-HAPLOTYPE AND OR DR 4-HAPLOTYPE DOES NOT LEAD TO ISLET AUTOIMMUNITY/

The hypothesis was tested that islet autoimmunity is induced by ongoin g 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 mic roscopy studies in 10 patients showed that the inflammatory process al so affected islets, as recognisable from islet cell lysis, intrainsula r fibrosis and immune cell infiltrates. None of the sera tested contai ned any of three markers of islet autoimmunity, ICA, IAA or GAD antibo dies. A correlation was seen between the loss of exocrine function, as determined by the ALTAB-test, and of beta-cell function, as determine d by the C-peptide response to i.v. glucagon. However, there was no pr eferential loss of beta-cell function in patients with HLA-DR 3 and/or DR 4. We conclude that islet cell destruction occurs during chronic p ancreatitis, but does not trigger islet autoimmunity, even in the pres ence of HLA-DR 3 and/or DR 4.