Pancreas Allograft Biopsies with Positive C4d Staining and Anti‐Donor Antibodies Related to Worse Outcome for Patients

Abstract

C4d+ antibody-mediated rejection following pancreas transplantation has not been well characterized. Therefore, we assessed the outcomes of 27 pancreas transplantation patients (28 biopsies), with both C4d staining and donor-specific antibodies (DSA) determined, from a cohort of 257 patients. The median follow-up was 50 (interquartile range [IQR] 8-118) months. Patients were categorized into 3 groups: group 1, patients with minimal or no C4d staining and no DSA (n = 13); group 2, patients with either DSA present but no C4d, diffuse C4d+ and no DSA or focal C4d+ and DSA (n = 6); group 3, patients with diffuse C4d+ staining and DSA (n = 9). Active septal inflammation, acinar inflammation and acinar cell injury/necrosis were significantly more abundant in group 3 than in group 2 (respective pvalues: 0.009; 0.033; 0.025) and in group 1 (respective p-values: 0.034; 0.009; 0.002). The overall uncensored pancreas graft survival rate for groups 1, 2 and 3 were 53.3%, 66.7% and 34.6%, respectively (p = 0.044). In conclusion, recipients of pancreas transplants with no C4d or DSA had excellent long-term graft survival in comparison with patients with both C4d+ and DSA present. Hence, C4d should be used as an additional marker in combination with DSA in the evaluation of pancreas transplant biopsies.

Impact of IgG3 Subclass and C1q-Fixing Donor-Specific HLA Alloantibodies on Rejection and Survival in Liver Transplantation

“…Moreover, antibody-mediated rejection (AMR) is now recognized as a cause of allograft loss in all solid organ transplants despite significant differences in incidence and outcome (6)(7)(8)(9)(10)(11). Historically, it has been recognized that the liver is relatively resistant to the pathologic effects of DSA compared to other solid organs (12)(13)(14)(15).…”

The current challenges for pancreas transplantation for diabetes mellitus

“…Similar observations have been made in pancreas transplantation where the presence of C4d in pancreas transplant biopsies together with circulating DSA has been shown to predict poorer graft survival [116]. Presence of C4d on interacinar capillaries now forms part of the Banff classification of antibody-mediated pancreatic rejection [117].…”

Preserved Endocrine Function in a Pancreas Transplant Recipient with Pancreatic Panniculitis and Antibody-Mediated Rejection

“…In their study of mostly alemtuzumab treated patients, the 9 C4d+/DSA+ biopsies were performed at a mean of POD 134 (range 5-336), with a mean fasting glucose of 106 (range 80-129; 2 above 110) (9). In a recent series, 9 C4d+/DSA+ pancreatic allograft biopsies (mean POD 52 days, median 21 days) and 6 C4d+ or DSA+ biopsies had worse graft outcome as compared to C4d-/DSA-biopsies, but glycemic data was not provided (10). Further studies of the relationship of pancreas antibody-mediated rejection to altered endocrine function are necessary.…”