Re-examination of the lymphocytotoxic crossmatch in liver transplantation: Can C4d stains help in monitoring?

J. Lunz, K. M. Ruppert, M. M. Cajaiba, K. Isse, C. A. Bentlejewski, M. Minervini, M. A. Nalesnik, P. Randhawa, E. Rubin, E. Sasatomi, M. E De Vera, P. Fontes, A. Humar, A. Zeevi, A. J. Demetris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


C4d-assisted recognition of antibody-mediated rejection (AMR) in formalin-fixed paraffin-embedded tissues (FFPE) from donor-specific antibody-positive (DSA+) renal allograft recipients prompted study of DSA+ liver allograft recipients as measured by lymphocytotoxic crossmatch (XM) and/or Luminex. XM results did not influence patient or allograft survival, or cellular rejection rates, but XM+ recipients received significantly more prophylactic steroids. Endothelial C4d staining strongly correlates with XM+ (<3 weeks posttransplantation) and DSA+ status and cellular rejection, but not with worse Banff grading or treatment response. Diffuse C4d staining, XM+, DSA+ and ABO- incompatibility status, histopathology and clinical-serologic profile helped establish an isolated AMR diagnosis in 5 of 100 (5%) XM+ and one ABO-incompatible, recipients. C4d staining later after transplantation was associated with rejection and nonrejection-related causes of allograft dysfunction in DSA- and DSA+ recipients, some of whom had good outcomes without additional therapy. Liver allograft FFPE C4d staining: (a) can help classify liver allograft dysfunction; (b) substantiates antibody contribution to rejection; (c) probably represents nonalloantibody insults and/or complete absorption in DSA- recipients and (d) alone, is an imperfect AMR marker needing correlation with routine histopathology, clinical and serologic profiles. Further study in late biopsies and other tissue markers of liver AMR with simultaneous DSA measurements are needed.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalAmerican Journal of Transplantation
Issue number1
StatePublished - Jan 2012


  • Allograft monitoring
  • antibody-mediated rejection
  • complement C4d
  • crossmatching
  • liver allograft

ASJC Scopus subject areas

  • Transplantation
  • Pharmacology (medical)
  • Immunology and Allergy


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