title: The clinical implications of the unique glomerular complement deposition pattern in transplant glomerulopathy.
abstract: The etiology and treatment of transplant glomerulopathy (TG) is not clear. TG is associated with donor-specific antibodies but the lack of C4d deposition in the peritubular capillaries (ptc-C4d) in some cases has caused the role of complement in the pathogenesis of TG to be debated. There is however, little information on C4d deposition in the glomerulus itself. We retrieved random frozen sections from 25 cases with well-established TG by light microscopy (LM) and 25 cases without TG as controls and reviewed the LM and immunofluorescence (nine biopsies were excluded due to inadequate samples). Glomerular complement deposition was assessed in all included biopsies. Glomerular C3d and C4d deposition occurred in a distinct pattern in all TG biopsies: segmental or global double linear staining of the glomerular capillary wall in 23 (100%). This pattern was not present in any NON-TG biopsies. The distinct glomerular complement deposition patterns in all TG cases are suggestive that TG is a proximal complement-mediated process and therapies should focus on proximal complement inhibition.
authors.affiliation: Division of Pediatric Nephrology, University of Minnesota, Minneapolis, USA. pverghes@umn.edu.
authors.forename: Priya S
authors.identifier: http://orcid.org/0000-0002-8836-0881
authors.initials: PS
authors.lastname: Verghese
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA.
authors.forename: Robin C
authors.initials: RC
authors.lastname: Reed
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, USA.
authors.forename: Bu
authors.initials: B
authors.lastname: Lihong
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis, USA.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Matas
authors.affiliation: Division of Pediatric Nephrology, University of Minnesota, Minneapolis, USA.
authors.forename: Youngki
authors.initials: Y
authors.lastname: Kim
mesh_terms: D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D003167:Complement Activation; D015933:Complement C3d / Q000032:analysis*; D015935:Complement C4b / Q000032:analysis*; D005455:Fluorescent Antibody Technique; D005629:Frozen Sections; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D010446:Peptide Fragments / Q000032:analysis*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d
keywords: Antibody mediated rejection; Chronic graft loss; Chronic rejection; Complement; Complement inhibition; TG