title: Peritubular Capillary Basement Membrane Multilayering in Renal Allograft Biopsies of Patients With De Novo Donor-Specific Antibodies.
abstract: BACKGROUND
  Severe peritubular capillary basement membrane multilayering (PTCBML) is part of the Banff definition of chronic antibody-mediated rejection. We retrospectively investigated whether assessment of the mean number of layers of basement membrane (BM) around peritubular capillaries (PTC) can be used in a cohort of patients with de novo donor-specific antibodies (dnDSA) as an early marker to predict long-term antibody-mediated injury.
  
  
  METHODS
  This is a retrospective cohort study with 151 electron microscopy samples from 54 patients with dnDSA, assessed at around 1 year after transplantation, for a mean number of BM layers around PTC and in serial biopsies. Graft survival and time to transplant glomerulopathy (TG) development were estimated in survival analyses.
  
  
  RESULTS
  We found that a mean PTCBML count greater than 2.5 layers assessed in a sample of 25 PTCs around 1 year after transplantation is indicative of the development of TG in patients with dnDSA (P = 0.001). In addition, in patients with serial biopsies available for electron microscopy analysis, we could distinguish 2 groups: patients with a mean PTCBML count of 2.5 or less on all biopsies, and patients who developed greater than 2.5 layers at any time after transplantation. The latter group reflected dnDSA patients at risk for TG development (P < 0.001). In patients with dnDSA, PTCBML score added significantly to the sensitivity and specificity of prediction of TG compared with microcirculation injury score alone.
  
  
  CONCLUSIONS
  Our results highlight the potential value of assessing the mean number of BM in PTC for early prediction of progression to chronic antibody-mediated injury.
authors.affiliation: 1 Centre for Complement and Inflammation Research, Department of Medicine, Imperial College Hammersmith Campus, London, United Kingdom. 2 Department of Histopathology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. 3 Department of Experimental Immunology/Renal Transplant Unit, Academic Medical Center, Amsterdam, The Netherlands. 4 Imperial College Kidney and Transplant Centre, London, United Kingdom. 5 Histocompatibility and Immunogenetics Laboratory, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. 6 Electron Microscopy Unit, Department of Histopathology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, United Kingdom.
authors.forename: Hanneke
authors.initials: H
authors.lastname: de Kort
authors.forename: Michelle
authors.initials: M
authors.lastname: Willicombe
authors.forename: Paul
authors.initials: P
authors.lastname: Brookes
authors.forename: Linda B
authors.initials: LB
authors.lastname: Moran
authors.forename: Eva
authors.initials: E
authors.lastname: Santos-Nunez
authors.forename: Jack W
authors.initials: JW
authors.lastname: Galliford
authors.forename: David
authors.initials: D
authors.lastname: Taube
authors.forename: Adam G
authors.initials: AG
authors.lastname: McLean
authors.forename: Jill
authors.initials: J
authors.lastname: Moss
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Candice
authors.initials: C
authors.lastname: Roufosse
mesh_terms: D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002196:Capillaries / Q000276:immunology* / Q000648:ultrastructure; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D050533:Glomerular Basement Membrane / Q000276:immunology* / Q000648:ultrastructure; D006084:Graft Rejection / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D006085:Graft Survival; D006801:Humans; D007518:Isoantibodies / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000098:blood supply*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D007518:Isoantibodies