Diffuse C4d staining and not the presence of donor specific antibody (DSA) is associated with decreased pancreas allograft survival

W. Manitpisitkul, N. Wilson, R. Munivenkatappa, R. Barth, D. Kukuruga, S. Bartlett, B. Philosophe
University of Maryland, Surgery, Baltimore, USA

Objective: The association of C4d deposition and DSA has not been well characterized for pancreas as it has for renal transplantation. The purpose of this study is to evaluate the effect and distribution pattern of C4d staining on graft survival, and its association with DSA

Methods: From 2000-2010, 322 pancreas transplants were performed at our center. Of 165 patients that had a pancreas biopsy for cause, 77 were stained for C4d. In concordance with renal Banff classification, C4d staining for these pancreas biopsies were classified as diffuse (>50% C4d+ IAC), focal (5% - 50), or negative (< 5%). DSA obtained at the time of biopsy were available for 23 of these patients. Pancreas allograft loss is defined as return to insulin therapy or patient death.

Results: 78% of the patients received Thymoglobulin and 22% received Campath induction. There was no significant difference in survival or rejection between the two groups. Diffuse C4d staining was significantly associated with the presence of DSA (MFI >1000) for either class I or class II (P = 0.002). In contrast, focal C4d staining had no association with presence of DSA (P=0.136). Four year pancreas allograft survival was significantly lower in patients with diffuse C4d+ when compared to those with focal or negative C4d staining (37.5%, 80% and 65.9%, respectively P = 0.012, figure 1), irrespective of DSA presence. The presence of DSA alone had no impact on four year graft survival (66.7% DSA+ vs. 53.4% DSA-, P=0.659).

Conclusions: Diffuse C4d deposition in pancreas biopsies has a negative impact on graft survival as shown with renal transplantation. In contrast, the presence of DSA itself was not a predictor of graft outcome. This data supports routine C4d staining for all pancreas biopsies and consideration for aggressive treatment when diffuse deposition is present, regardless of DSA data.