HETEROGENEITY OF ISLET PATHOLOGY IN 2 INFANTS WITH RECENT-ONSET DIABETES-MELLITUS

The mechanisms by which the beta cells of pancreatic islets are destro yed in insulin-dependent diabetes mellitus (IDDM) are poorly understoo d. In this report the pancreatic histo- and immunopathology of two chi ldren, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebra l oedema within a day of clinical diagnosis of IDDM, were investigated . Patient 1, a 14-month-old girl, had a 4-week history of polydipsia a nd polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed mar kedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonst rated in both patients with the HAM-56 monoclonal antibody. Neither pa tient showed aberrant expression of HLA class II antigens on insulin-i mmunoreactive cells, but allele-specific HLA-DQ8 expression was eviden t on endothelial cells. Glutamic acid decarboxylase immunoreactivity w as detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insuli tis, may reflect different dynamics and extent rather than different p athomechanisms of immune destruction of islets in IDDM.