title: A Banff Component Scoring-based Histologic Assessment of Bortezomib-based Antibody-mediated Rejection Therapy.
abstract: BACKGROUND
  Histology remains a cornerstone for antibody-mediated rejection (AMR) diagnosis. Little data exist supporting histology for assessing therapeutic responses. This study evaluates histologic components in assessing AMR therapeutic responses.
  
  
  METHODS
  Antibody-mediated rejection was diagnosed using Antibody Working Group criteria and Banff component scoring, and C4d staining data were analyzed. Statistics included independent and paired samples t test, χ(2), Fisher exact, or the Wilcoxon-signed rank test. Fifty-five AMR patients were analyzed. Early AMR was defined as occurring within 6 months after transplantation and treated with a single rituximab dose and 4 bortezomib doses preceded by plasmapheresis. Allograft biopsies were performed within 48 hours of treatment; repeat biopsy was performed 14 to 21 days later.
  
  
  RESULTS
  Early AMR demonstrated histologic improvement in mean scores for acute Banff components glomerulitis (g), C4d, g+ peritubular capillaritis (ptc) and acute composite score, but showed deterioration in chronic Banff components tubular atrophy and interstitial fibrosis. Late AMR showed improved mean scores for acute Banff components tubulitis, interstitial inflammation, g, ptc, g + ptc, C4d, and acute composite score, but chronic scores did not change. Significant changes in distribution of Banff scores after treatment were observed for g, C4d, tubular atrophy, and interstitial fibrosis scores in early AMR patients and tubulitis, interstitial inflammation, g, ptc, and C4d in late AMR.
  
  
  CONCLUSIONS
  These results show that: (1) Banff component scoring provides insights into histologic responses to AMR therapy and may provide a potential endpoint for clinical AMR trials. (2) Early and late AMR demonstrate differences in acute and chronic Banff components at the time of the AMR diagnostic biopsy, as well as differential responses to AMR therapy.
authors: 1 Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH. 2 Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH. 3 The Christ Hospital, Cincinnati, OH. 4 Department of Pathology, The Christ Hospital, Cincinnati, OH. 5 Department of Pathology, University of Cincinnati College of Medicine, Cincinnati, OH. 6 Department of Pathology, Cincinnati Children's Hospital, Cincinnati, OH.
authors: Basma
authors: B
authors: Sadaka
authors: Nicole S
authors: NS
authors: Ejaz
authors: Adele R
authors: AR
authors: Shields
authors: Michael A
authors: MA
authors: Cardi
authors: George
authors: G
authors: Wadih
authors: David
authors: D
authors: Witte
authors: Bassam G
authors: BG
authors: Abu Jawdeh
authors: Rita R
authors: RR
authors: Alloway
authors: E Steve
authors: ES
authors: Woodle
mesh_terms: D000208:Acute Disease; D000328:Adult; D001284:Atrophy; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D016009:Chi-Square Distribution; D002908:Chronic Disease; D015935:Complement C4b / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005355:Fibrosis; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011237:Predictive Value of Tests; D011719:Pyrazines / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001897:Boronic Acids; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D011719:Pyrazines; D000069286:Bortezomib; D015935:Complement C4b; C032261:complement C4d