Pancreatic biopsy to detect insulitis in type 1 diabetes

Original article:
Pancreatic biopsy as a procedure for detecting in situ autoimmune phenomena in type 1 diabetes. Close correlation between serological markers and histological evidence of cellular autoimmunity. Imagawa A, Hanafusa T, Tamura S, Moriwaki M, Itoh N, Yamamoto K, Iwahashi H, Yamagata K, Waguri M, Nanmo T, Uno S, Nakajima H, Namba M, Kawata S, Miyagawa J, Matsuzawa Y. Diabetes 2001; 50: 1269–73.

Summary
The authors performed pancreatic biopsies in 29 patients with recent-onset type 1 diabetes to investigate the presence of autoimmune phenomena occurring in type 1 diabetes. The patients’ mean age was 28 years and the duration of diabetes was approximately 3 months. The biopsies entailed no serious complications such as bleeding, peritonitis or pancreatitis. Two patients experienced pneumoderma and dull abdominal pain. Lymphocyte infiltration in the islets was observed. The T-cell-predominant subpopulation was characterized by CD8+ cells. There was also hyperexpression of major histocompatibility complex (MHC) class I antigens on islet cells, observed in half of the patients studied.
The authors conclude that pancreatic biopsy is a safe procedure which may help in defining the autoimmune phenomena occurring in patients with type 1 diabetes.

Comment
Type 1 diabetes is thought to be an immune-mediated disease occurring in genetically predisposed individuals. Defining the (auto)immune response towards islet b-cells is important, as it may suggest ways of preventing their destruction. In this context, the present paper describes a new procedure to investigate the autoimmune phenomena occurring in type 1 diabetic patients shortly after clinical diagnosis. The use of laparoscopy for characterizing the immunological features in the islets may be viewed either as acceptable or as dangerous and unethical. Nevertheless, this paper is of great interest, as it may help to clarify some of the mechanisms involved in the damage to b-cells leading to type 1 diabetes.
The main findings reported in this paper were not unexpected; however, hyperexpression of MHC class I antigens was a novel finding. Infiltration of CD8+ cells was in line with previous reports on pancreatic tissues analysed on postmortem samples. It is surprising that only one patient showed MHC class II hyperexpression on islet cells, since there had been a general consensus that hyperexpression of MHC class II was present on islet cells of type 1 diabetic patients, as reported in 1985 by Bottazzo and co-workers [1]. Another interesting observation was that the majority of cells infiltrating the pancreas were CD8+ T-lymphocytes, but macrophage-predominant insulitis was observed only in two patients. Also of interest was the finding that B-lymphocyte-predominant insulitis was not observed in any of the patients.
The results of this study could shed new light on the possible causes of b-cell destruction. They strongly support the concept that CD8+ T cells play a crucial role in the pathogenesis of type 1 diabetes. The recent paper by Martin et al. [2], which described a boy with X-linked agammaglobulinaemia who developed type 1 diabetes, argues in favour of cell-mediated destruction of the b-cells.
Finally, a comment should be made in relation to the procedure of pancreatic biopsy. This is not an easy technique; it is difficult to accept in a patient with type 1 diabetes, except under strict ethical permission and justified for understanding the potential mechanisms involved in the destruction of b-cells. It should be mentioned that this procedure does not help the patient and it is very unlikely that it will give further indication as to how the patient should be treated. Therefore I personally think that pancreatic biopsy should not be repeated in other clinical settings because this paper offers sufficient useful information.

References
1. Bottazzo GF, Dean BM, McNally JM et al. In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 1985; 313(6): 353–60.
2. Martin S, Wolf-Eichbaum D, Duinkerken G et al. Development of type 1 diabetes despite severe hereditary B-lymphocyte deficiency. N Engl J Med 2001; 345(14): 1036–40.