title: The impact of C4d staining as a humoral injury marker.
abstract: OBJECTIVE
  Acute and chronic humoral injuries in renal transplant recipients are the main reasons for graft rejection and failure. Histological and clinical characteristics of humoral rejection and symptoms are variable and not always helpful for differential diagnosis. Clinical monitoring of the allograft, an elevated serum panel-reactive antibody (PRA), and the presence of donor-specific antibody (DSA) during immune monitoring as well as C4d staining of biopsy material can establish the differential diagnosis. Even without a cellular component, humoral rejection reaction is serious because the target tissue is the graft endothelium. Because the kidney graft has a rich vascular structure this attack causes permanent injury to the kidney in the long term. Graft dysfunction in this setting is usually more severe, requiring dialysis therapy, compared with acute cellular reactions. Positive C4d staining of peritubular capillaries in biopsy material represent a hallmark of complement-dependent cytotoxicity, supporting the diagnosis of humoral rejection. We analyzed C4d staining as a hallmark of humoral rejection.
  
  
  METHODS
  From 2009 to 2011, we analyzed the relationship between pathological findings of C4d immunohistochemistry staining and the clinical outcomes of 45 kidney transplant recipients who underwent a kidney biopsy because of graft dysfunction due to possible humoral rejection.
  
  
  RESULTS
  Biopsy specimens of 15 patients stained C4d positive; the remaining 30 showed negative results. Intravenous steroids, PP + IVIG with or without antithymocyte globulin (ATG), was administered for treatment. Sixty six percent (n = 10) of patients were C4d positive with 16% (n = 5) of those showing C4d-negative biopsy results, losing their grafts, and returning to hemodialysis.
  
  
  CONCLUSIONS
  C4d staining refractory humoral rejection injury was related to poor graft outcomes.
authors: First General Surgery, Transplantation and Genetics Units, Haydarpasa Numune Research and Training Hospital, Istanbul, Turkey. drvmelihkara@yahoo.com
authors: M
authors: M
authors: Kara
authors: F
authors: F
authors: Demir
authors: P
authors: P
authors: Ata
authors: L
authors: L
authors: Ozel
authors: G
authors: G
authors: Gumrukcu
authors: E
authors: E
authors: Unal
authors: M
authors: M
authors: Canbakan
authors: M
authors: M
authors: Gucun
authors: V
authors: V
authors: Esadoglu
authors: E
authors: E
authors: Ozdemir
authors: H
authors: H
authors: Cemel
authors: M I
authors: MI
authors: Titiz
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D015935:Complement C4b / Q000032:analysis*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D006085:Graft Survival; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000032:analysis*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014421:Turkey
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d