RECURRENT DIABETES-MELLITUS IN THE PANCREAS ISOGRAFT AND ALLOGRAFT - A LIGHT AND ELECTRON-MICROSCOPIC AND IMMUNOHISTOCHEMICAL ANALYSIS OF 4 CASES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 53  (2) , 132-144
Abstract
Four patients with type 1 diabetes mellitus received segmental pancreatic grafts. The donors were HLA-identical twins in 3 patients and an HLA-identical sibling in 1. Each patient had normal glucose metabolism in the posttransplantation period but impaired graft function developed after 6-12 wk. Complete loss of function developed in 3 patients. The 4th patient received immunosuppressive therapy but continues to require a low dose of insulin 15 mo. following transplantation. Pancreatic graft biopsy at the time of declining graft function in 3 patients revealed a mononuclear cell infiltrate centered upon islets consisting of variable numbers of T11 (pan T), OKT8 (suppressor-killer), OKT9 (transferrin receptor), OKT10 (activated) and HLA-DR-reactive mononuclear cells, as well as 63D3 and OKM1 reactive monocytes. Biopsies obtained following loss of graft function revealed resolution of the inflammatory process and selective destruction of all islet .beta.-cells in 2 patients, whereas graft biopsy in 1 patient demonstrated a mononuclear cell infiltrate in islets containing demonstrable .beta.-cells but no infiltrate in islets without .beta.-cells. Following immunosuppressive therapy the 4th patient showed resolution of the insulitis and destruction of .beta.-cells in 70% of the islets. The variable numbers of .beta.-cells observed in the remaining islets likely account for the relatively low amount of exogenous insulin required by this patient. There was no immunohistologic evidence of humoral mediated immune reaction in any of the biopsies. Selective .beta.-cell destruction was a consequence of cell-mediated immunity leading to recurrent diabetes mellitus.