title: Re-examination of sinusoidal deposition of complement 4d in liver allografts: experience from a single institution.
abstract: Complement 4d (C4d) is a marker of complement activation that has been used to evaluate humoral rejection in renal and heart allografts. Studies suggested a role for C4d detection in liver allografts in diagnosing acute cellular and humoral rejection but none correlated this with the pre-transplant liver disease. Our study analyzed the association of C4d deposition in liver allografts with the pre-transplant liver disease. C4d deposition was evaluated by indirect immunofluorescence and correlated with lymphocytotoxic crossmatch results, post-transplant clinicopathological diagnosis and type of pre-transplant liver disease. Allograft biopsies were classified by the native liver disease. After excluding 20 patients with rare liver diseases; C4d deposition was evaluated in 506 biopsies from 310 patients including 25 with PSC, 198 with viral hepatitis and 87 with other diseases. C4d immunereactivity distribution was not different among biopsies from patients with different lymphocytotoxic crossmatch results. Sinusoidal C4d deposition was noted in 11.9% of biopsies and 15.2% of patients (in one or more biopsies). 26% (9/35) of biopsies from patients with PSC had sinusoidal C4d deposition; more frequently than from patients with viral hepatitis 12% (43/348) (p=0.04) and other liver diseases 7% (8/123) (p=0.005). In conclusion, C4d deposition in liver allografts is independent of the crossmatch results. It occurs with a variety of pathologic abnormalities and underlying liver diseases; but is more frequent in patients with PSC. This suggests that mechanisms other than allo-immunity activate complement. The mechanisms and clinical significance of C4d deposition in liver allografts in patients with PSC remain to be determined.
authors.affiliation: Department of Internal Medicine, Medicine Institute, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Mohannad
authors.initials: M
authors.lastname: Dugum
authors.affiliation: Transplantation Center, Digestive Disease Institute, Cleveland Clinic Cleveland, OH, USA ; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, OH, USA.
authors.forename: Medhat
authors.initials: M
authors.lastname: Askar
authors.affiliation: Anatomic Pathology, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Rish K
authors.initials: RK
authors.lastname: Pai
authors.affiliation: Anatomic Pathology, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Yerian
authors.affiliation: Anatomic Pathology, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Bennett
authors.affiliation: Anatomic Pathology, Cleveland Clinic Cleveland, OH, USA.
authors.forename: James
authors.initials: J
authors.lastname: McMahon
authors.affiliation: Cleveland Clinic Lerner College of Medicine of Case Western Reserve University Cleveland, OH, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Xie
authors.affiliation: Transplantation Center, Digestive Disease Institute, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Bijan
authors.initials: B
authors.lastname: Eghtesad
authors.affiliation: Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Hanouneh
authors.affiliation: Anatomic Pathology, Cleveland Clinic Cleveland, OH, USA.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Liu
mesh_terms: D064591:Allografts; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003167:Complement Activation; D015935:Complement C4b / Q000032:analysis*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D008099:Liver / Q000276:immunology* / Q000601:surgery*; D008107:Liver Diseases / Q000276:immunology* / Q000601:surgery*; D016031:Liver Transplantation; D009820:Ohio; D010446:Peptide Fragments / Q000032:analysis*; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: Liver allograft; complement; lymphocytotoxic antibody; primary sclerosing cholangitis; rejection