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Abstract: FR-PO879

C4d Staining Following Thymoglobulin Treatment for Acute Cellular Rejection

Session Information

Category: Transplantation

  • 1802 Transplantation: Clinical

Authors

  • Taylor, Veronica A., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Maniar, Aesha, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
  • Witte, David P., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
  • Dixon, Bradley P., Children's Hospital of Colorado, Aurora, Colorado, United States
  • Hooper, David K., Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
Background

Rejection is an important cause of allograft failure in kidney transplant recipients (KTRs). Treatment is guided by histologic and biochemical findings indicating cellular and/or humoral origin. C4d staining is one of the diagnostic criteria for antibody mediated rejection (ABMR). At our center we observed an increase in C4d staining on some biopsies following thymoglobulin treatment for acute T-cell mediated rejection (TCMR).

Methods

We performed retrospective review of all KTRs at our pediatric center from January 2013 to April 2018 who received thymoglobulin treatment for acute TCMR and who had a follow-up biopsy within 45 days of diagnosis. Patients who had C4d staining or other histologic evidence of ABMR on initial biopsy were excluded. We evaluated C4d staining on repeat biopsy and compared patients who did not have existing or de novo donor specific antibodies (DSAs) within 12 months of diagnosis to those who did.

Results

14 KTRs received an average of 12.7mg/kg of thymoglobulin over 4-14 days. Mean time between TCMR diagnosis and follow-up biopsy was 14.9 days. 8 patients remained negative for DSAs during the defined peri-rejection period. Of the 6 patients found to have positive DSAs, 1 showed persistence of known chronic class II DSAs and 5 developed de novo DSAs (4 within 6 weeks of TCMR diagnosis and 1 at 7 months). Post-thymoglobulin C4d staining increased in all 6 DSA-positive patients but only 3/8 (37.5%) of DSA-negative patients (p=0.03). Histologic evidence of ABMR (capillaritis) on follow-up biopsy was seen in two patients with de novo DSAs.

Conclusion

Positive C4d staining can be seen following thymoglobulin treatment of rejection even in the absence of DSAs. C4d staining increased following thymoglobulin therapy in all patients with DSAs, sometimes before the DSA was detectable. These findings may indicate thymoglobulin enhancement of complement activation by DSAs, non-DSA ABMR, or independent in situ complement activation facilitated by the polyclonal xenoantibody preparation.

C4d staining following thymoglobulin treatment of TCMR
C4d StainingNegative DSA (n=8)Positive DSA (n=6)
Negative or Nonspecific Glomerular and Tubular50
Glomerular without PTC13
PTC11
Diffuse (Glomerular & PTC)12

PTC, peritubular capillaries