title: Complement component 4d immunostaining in liver allografts of patients with de novo immune hepatitis.
abstract: De novo immune hepatitis (DNIH) is a form of late graft dysfunction after liver transplantation. The fine mechanisms leading to the development of DNIH are not known, and whether this hepatitis is a form of rejection or a result of an auto/alloimmune injury has not been established. In our patients, DNIH was always preceded by the production of donor-specific antibodies against the glutathione S-transferase T1 (GSTT1) enzyme because of a genetic mismatch in which the donors carried the wild-type gene and the recipients displayed the null genotype. Complement component 4d (C4d) immunopositivity in 12 paraffin-embedded liver biopsy samples from 8 patients diagnosed with DNIH associated with anti-GSTT1 antibodies was retrospectively evaluated. Six patients with a diagnosis of chronic rejection (CR) and 7 patients with hepatitis C virus recurrence were included as control groups. Among the patients with DNIH, 7 showed C4d-positive immunostaining localized in the portal tracts, whereas in the tested biopsy samples of the 2 control groups, this staining pattern was absent. Four biopsy samples of the CR group showed C4d-positive sinusoidal staining. This study confirms the activation of the complement pathway in the presence of donor-specific antibodies, which was shown by the deposition of C4d elements in liver biopsy samples of patients with DNIH. The use of C4d as a marker of antibody-mediated rejection in liver allografts in the presence of antidonor antibodies is discussed, and it may contribute to improved differential diagnoses based on biopsy findings.
authors.affiliation: Immunology, Biomedicine Institute of Seville, Virgen del Rocío University Hospital, Seville, Spain. isabel.aguilera.exts@juntadeandalucia.es
authors.forename: Isabel
authors.initials: I
authors.lastname: Aguilera
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Sousa
authors.forename: Francisco
authors.initials: F
authors.lastname: Gavilan
authors.forename: Lourdes
authors.initials: L
authors.lastname: Gomez
authors.forename: Antonia
authors.initials: A
authors.lastname: Alvarez-Márquez
authors.forename: Antonio
authors.initials: A
authors.lastname: Núñez-Roldán
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D015935:Complement C4b / Q000737:chemistry*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D006505:Hepatitis / Q000209:etiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry*; D012008:Recurrence; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase