Prevalence & significance of pancreatic islet cell & adrenal antibodies in patients with Graves' disease.

The prevalence of adrenocortical (ACAb), islet cell (ICAb) and thyroid microsomal (TMAb) autoantibodies was determined by indirect immunofluorescence, in 88 consecutive patients with Graves' disease. ACAb, ICAb and TMAb positivity was seen in 3 (3.3%), 10 (11%) and 66 (75%) patients respectively. Among these one patient had both ACAb and ICAb positivity. Diabetes mellitus was found to be present in two (2.3%; both ICAb positive) of the 88 patients studied. Two of the four ICAb positive patients had loss of first phase insulin response to intravenous glucose. A significant proportion of patients of Graves' disease had associated islet cell and/or adrenal autoimmunity. A high index of suspicion for associated endocrine autoimmunity should be maintained while dealing with subjects of Graves' disease.

Islet cell antigens and autoantigen(s): Monoclonal antibodies and further characterization.

A novel series of murine monoclonal antibodies to islet cells (I-45, I-51, I-52 and I-39) have been generated using human insulinoma homogenate as the immunogen in order to characterize pathogenetically relevant islet cell autoantigen(s). Differentiation antigens recognized by these islet cell monoclonal antibodies displayed varied cytological distribution (pan-islet or peripheral mantle only). Monoclonal antibody I-45 reacted with all endocrine subsets of the pancreatic islet, similar to the reactivity of islet cell autoantibody positive sera from type I diabetes subjects. Preexposure to pH2 abolished the immunoreactivity of the autoantigen; I-45 antigen was also sensitive to low pH. Preexposure to 100° C for 1 h did not significantly alter the immunoreactivity of islet antigens recognized by ICAb positive patient sera and monoclonal antibody 1-39, thus demonstrating the extraordinary heat stability of the corresponding epitopes; those recognized by I-45 were less heat stable. Islet cells were found to share I-45 differentiation antigen(s)/epitope(s) with other neuroendocrine cells, viz. amerior pituitary, adrenal medulla and gut endocrine cells.

Pancreatic islet transplantation: utility of ductular obstruction and exocrine atrophy model?

Introduction of 'silent' exocrine atrophy (and endocrine 'enrichment') in pancreatic grafts following ductular blockade may have a role in human diabetes by circumventing currently elusive islet isolation/purification protocols. To explore this potential, pancreatic isografts were performed in 12 pairs of inbred Wistar NIN rats. Donor pancreatectomy was performed after distal clamping and canulation of common bile duct and injection of 0.5 ml. polyacrylamide gel (blocked n = 7) or normal saline (un-blocked n = 5) respectively. One to 2 m.m. fragments of the resulting mildly distended pancreases were transplanted in to 2 sites (renal capsule and iliac fossa subcutaneously) of cach recipient. Post-operative biopsies of the transplanted grafts (unilateral nephrectomy and iliac fossa biopsies) revealed macroscopic and microscopic evidence of necrotizing pancreatitis in both the groups at both the sites (histiocytic and giant cell infiltration, fat necrosis and focal calcification with destruction of exocrine and endocrine cells) as early as 1 and 3 weeks. Possible detrimental factors include: volume and pressure of ductal injection, graft sites (confined spaces), post-operative wound infection and bio-compatibility of the material used for ductular blockade.