title: Glomerular C3c deposition and intravascular macrophage accumulation in early humoral renal allograft rejection signifies a poor short-term outcome.
abstract: C4d deposition in the walls of peritubular capillaries is considered the key phenomenon in the histopathological diagnosis of humoral, i.e. antibody-mediated, allograft rejection. We have earlier proposed that deposition of C3c in glomerular capillaries and simultaneous intravascular accumulation of macrophages in allografts with immediate or early humoral rejection indicates a potentially serious condition with very poor prognosis. The clinical outcome of 45 cadaveric grafts with this phenomenon among 1960 renal allografts transplanted at our centre during 1984-1999, and the recipients of the contralateral kidneys, was retrospectively evaluated. Graft failure occurred in 44/45 grafts within 3 weeks, with graft loss in 33/45 (77%) within 4 months and 37/45 (82%) within 1 year. From the contralateral kidneys, 5/33 (15%) were lost within 1 year. In a recent series of early biopsies, we recognised that of 13 cases showing C4d positivity in peritubular capillaries but lacking C3c in glomeruli, 10/13 (77%) were still functioning after 4 months. The mean number of CD68(+) macrophages per glomerular profile, i.e. the glomerular macrophage index, shows a significant difference between C4d(+)C3c(-) and C4d(+)C3c(+) cases (p<0.001). Our results indicate the existence of a clinically important subgroup of early humoral rejection with particular morphological features.
authors.affiliation: Department of Clinical Pathology and Cytology, Sahlgrenska University, Göteborg, Sweden. Johan.Molne@vgregion.se
authors.forename: Johan
authors.initials: J
authors.lastname: Mölne
authors.forename: Gudrun
authors.initials: G
authors.lastname: Nyberg
authors.forename: Ingemar
authors.initials: I
authors.lastname: Blohmé
authors.forename: Lennart
authors.initials: L
authors.lastname: Rydberg
authors.forename: Michael E
authors.initials: ME
authors.lastname: Breimer
authors.forename: Christian T
authors.initials: CT
authors.lastname: Svalander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D002102:Cadaver; D002196:Capillaries / Q000276:immunology; D015932:Complement C3c / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000098:blood supply / Q000473:pathology; D007958:Leukocyte Count; D008264:Macrophages / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D015932:Complement C3c; C067980:CD68 antigen, human; D000097382:CD68 Molecule