Detailed Analysis of Simultaneous Renal and Liver Allografts in the Presence of DSA

Jacqueline G. O’Leary, MD, MPH; Alton B. Farris, MD; Howard M. Gebel, PhD; Sumeet K. Asrani, MD; Medhat Askar, PhD; Vanessa Garcia, BS; George J. Snipes, MD; Denise J. Lo, MD; Stuart J. Knechtle, MD; Goran B. Klintmalm, MD, PhD; Anthony J. Demetris, MD

doi:10.1097/TXD.0000000000001500

Transplantation Direct (Aug 2023)

Detailed Analysis of Simultaneous Renal and Liver Allografts in the Presence of DSA

Jacqueline G. O’Leary, MD, MPH,
Alton B. Farris, MD,
Howard M. Gebel, PhD,
Sumeet K. Asrani, MD,
Medhat Askar, PhD,
Vanessa Garcia, BS,
George J. Snipes, MD,
Denise J. Lo, MD,
Stuart J. Knechtle, MD,
Goran B. Klintmalm, MD, PhD,
Anthony J. Demetris, MD

Affiliations

Jacqueline G. O’Leary, MD, MPH: 1 Department of Medicine, Dallas VA Medical Center, Dallas, TX.
Alton B. Farris, MD: 2 Department of Pathology, Emory University Hospital, Atlanta, GA.
Howard M. Gebel, PhD: 2 Department of Pathology, Emory University Hospital, Atlanta, GA.
Sumeet K. Asrani, MD: 3 Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas TX.
Medhat Askar, PhD: 3 Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas TX.
Vanessa Garcia, BS: 3 Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas TX.
George J. Snipes, MD: 4 Department of Pathology, Baylor University Medical Center, Dallas TX.
Denise J. Lo, MD: 5 Department of Surgery, Duke University, Durham, NC.
Stuart J. Knechtle, MD: 5 Department of Surgery, Duke University, Durham, NC.
Goran B. Klintmalm, MD, PhD: 3 Annette C. & Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas TX.
Anthony J. Demetris, MD: 6 Department of Pathology, University of Pittsburgh, Pittsburgh, PA.

DOI: https://doi.org/10.1097/TXD.0000000000001500
Journal volume & issue: Vol. 9, no. 8
p. e1500

Abstract

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Background. Liver allografts protect renal allografts from the same donor from some, but not all, preformed donor specific alloantibodies (DSA). However, the precise mechanisms of protection and the potential for more subtle alterations/injuries within the grafts resulting from DSA interactions require further study. Methods. We reevaluated allograft biopsies from simultaneous liver-kidney transplant recipients who had both allografts biopsied within 60 d of one another and within 30 d of DSA being positive in serum (positive: mean florescence intensity ≥5000). Routine histology, C4d staining, and specialized immunohistochemistry for Kupffer cells (KCs; CD163) and a C4d receptor immunoglobulin-like transcript-4 were carried out in 4 patients with 6 paired biopsies. Results. Overt antibody-mediated rejection was found in 3 of 4 renal and liver allografts. One patient had biopsy-confirmed renal and liver allograft antibody-mediated rejection despite serum clearance of DSA. All biopsies showed KC hypertrophy (minimal: 1; mild: 2; moderate: 1; severe: 2) and cytoplasmic C4d KC staining was easily detected in 2 biopsies from 2 patients; minimal and negative in 2 biopsies each. Implications of which are discussed. Control 1-y protocol liver allograft biopsies from DSA– recipients showed neither KC hypertrophy nor KC C4d staining (n = 6). Conclusions. Partial renal allograft protection by a liver allograft from the same donor may be partially mediated by phagocytosis/elimination of antibody and complement split products by KCs, as shown decades ago in controlled sensitized experimental animal experiments.

Published in Transplantation Direct

ISSN: 2373-8731 (Online)
Publisher: Wolters Kluwer
Country of publisher: United States
LCC subjects: Medicine: Surgery
Website: http://journals.lww.com/transplantationdirect/Pages/default.aspx

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