title: Re-examination of the lymphocytotoxic crossmatch in liver transplantation: can C4d stains help in monitoring?
abstract: 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.
authors: Department of Pathology, Division of Transplantation, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors: J
authors: J
authors: Lunz
authors: K M
authors: KM
authors: Ruppert
authors: M M
authors: MM
authors: Cajaiba
authors: K
authors: K
authors: Isse
authors: C A
authors: CA
authors: Bentlejewski
authors: M
authors: M
authors: Minervini
authors: M A
authors: MA
authors: Nalesnik
authors: P
authors: P
authors: Randhawa
authors: E
authors: E
authors: Rubin
authors: E
authors: E
authors: Sasatomi
authors: M E
authors: ME
authors: de Vera
authors: P
authors: P
authors: Fontes
authors: A
authors: A
authors: Humar
authors: A
authors: A
authors: Zeevi
authors: A J
authors: AJ
authors: Demetris
mesh_terms: D000328:Adult; D000368:Aged; D015935:Complement C4b / Q000276:immunology*; D005260:Female; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d