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

  1. H. De Kort1,*,
  2. R. B. Munivenkatappa5,†,
  3. S. P. Berger2,
  4. M. Eikmans4,
  5. A. Van Der Wal1,
  6. E. J. De Koning2,
  7. C. Van Kooten2,
  8. E. De Heer1,
  9. R. N. Barth5,
  10. J. A. Bruijn1,
  11. B. Philosophe5,
  12. C. B. Drachenberg3,
  13. I. M. Bajema1

Article first published online: 23 APR 2010

DOI: 10.1111/j.1600-6143.2010.03079.x

Issue

American Journal of Transplantation

American Journal of Transplantation

Volume 10, Issue 7, pages 1660–1667, July 2010

Additional Information

How to Cite

De Kort, H., Munivenkatappa, R. B., Berger, S. P., Eikmans, M., Van Der Wal, A., De Koning, E. J., Van Kooten, C., De Heer, E., Barth, R. N., Bruijn, J. A., Philosophe, B., Drachenberg, C. B. and Bajema, I. M. (2010), Pancreas Allograft Biopsies with Positive C4d Staining and Anti-Donor Antibodies Related to Worse Outcome for Patients. American Journal of Transplantation, 10: 1660–1667. doi: 10.1111/j.1600-6143.2010.03079.x

Author Information

  1. 1

    Pathology

  2. 2

    Nephrology, Leiden University Medical Center, Leiden, The Netherlands

  3. 3

    Department of Pathology, University of Maryland School of Medicine, Baltimore, MD

  4. 4

    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

  5. 5

    Department of Surgery, University of Maryland School of Medicine, Baltimore, MD

  1. †

    Equal contributing author.

*Corresponding author: Hanneke de Kort, H.de_Kort@lumc.nl

Publication History

  1. Issue published online: 25 JUN 2010
  2. Article first published online: 23 APR 2010
  3. Received 09 September 2009 and accepted for publication 03 February 2010

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Keywords:

  • Allograft failure;
  • antibodies;
  • antibody-mediated rejection;
  • classification;
  • complement C4d;
  • donor-specific antibodies;
  • histopathology;
  • humoral rejection;
  • immunohistochemistry;
  • pancreas transplantation

This is the first pancreas transplant biopsy study in which antibody-mediated rejection as defined by positive C4d staining and donor specific antibodies was shown to correlate with worse long term graft survival, and with the pathological features of active septal and acinar inflammation and acinar cell injury/necrosis. See editorial by Colvin on page 1509.

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 p-values: 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.

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