Increased leucocytic infiltration of islets and exocrine tissue in organ donors with prolonged duration of life support

Background and aims: Leucocytic infiltration of the human endocrine pancreas is considered to be thehall-mark of recent onset type 1 diabetes in young patients. Recently, it has been proposed that a moregeneral infiltration of both endocrine and exocrine pancreas can be found in most type 1 and type 2diabetic patients. To interpret these findings, it is important to have insight into the variability ofleucocytic infiltration in the normal pancreatic gland in function of the clinical characteristics of thepatient. This study assesses the correlation between the duration of life support and the presence of aleucocytic infiltrate in human donor pancreas. It extends our previous observations, usingimmunophenotyping to identify and quantify the infiltrating leucocytes, study the kinetics of theinfiltration in a series of organ donors with increasing duration of life support, and differentiate betweeninfiltration in the exocrine tissue and in the endocrine pancreas. Materials and methods: Pancreas biopsy specimens from non-diabetic organ donors with differentduration of life support (0, 3, 6, 9 and ≥12 days) were used (n=10 per time point). Sections were doublestainedfor CD68, CD45, CD3, CD8 and CD20 in combination with insulin and digitally imaged toquantify the number of leucocytic cells in total pancreas and islets of Langerhans. Results: Donor pancreata from patients with a short duration of life support (0-3 days) showed low levelsof infiltrating leucocytic cells. Infiltration levels strongly increased from 6 - ≥12 days of life supportonwards: CD68+ cells were found to increase 10-fold between day 0 and day 6 (p<0.0125), remaining atelevated levels at day 9 and ≥12 (p<0.0025), with up to 9% of total cells found to be CD68+ in somedonors (Figure 1). CD45+, CD3+, CD8+ and CD20+ cells were less markedly increased, with asignificant (p<0.0125) 5-fold increase for CD45 and a significant (p<0.0125) 2-fold change for CD8 andCD20 between day 0 and day 9. The number of CD68+ cells in the islets showed a significant 2.5-foldincrease between 0 and ≥12 days (p<0.05), whereas other leucocyte cell types were present in lownumbers and did not show significant changes between the two groups. Conclusion: These results show that increased duration of life support is associated with increasedleucocytic infiltration in the endocrine and exocrine human donor pancreas from day 6 of life supportonwards, affecting 15-33% of pancreatic organ donors. The effect is strongest for CD68+ cells. Clinicalconditions around the time of organ retrieval should therefore be taken into account when studyinginflammatory lesions in the diabetic pancreas and necessitate adequate matching of patient samples.