title: Tubuloreticular Inclusions in Renal Allografts Associate with Viral Infections and Donor-Specific Antibodies.
abstract: The presence of tubuloreticular inclusions (TRIs) in native glomerular endothelial cells associates with viral infections and lupus nephritis. However, the associations of TRIs in renal transplant biopsy specimens are not known. We analyzed data from 316 patients who had a transplant biopsy with electron microscopy examination; 41 of 316 (13.0%) patients had TRIs. Patients with TRIs had significantly lower allograft survival rates (50.9%) than patients without TRIs (74.3%; P=0.03). Transplant glomerulopathy-free survival was also inferior in the TRI-positive group (57.5%) compared with the TRI-negative group (87.3%; P=0.002). Serologically, hepatitis C associated with the presence of TRIs (P=0.04) along with donor-specific antibodies (P=0.01). Furthermore, patients who were TRI positive were more likely than patients who were TRI negative to have had a previous rejection episode (P=0.02). On multivariate analysis, TRIs associated with prior rejection, viral infections, and class 1 HLA donor-specific antibodies. These results show that the presence of TRIs in renal allograft biopsy specimens associates with poor allograft outcomes and serologic evidence of viral infections and alloimmunity. The association with alloimmunity is a novel finding that warrants additional investigation.
authors.affiliation: Imperial College Renal and Transplant Centre, Michelle.Willicombe@imperial.nhs.uk.
authors.forename: Michelle
authors.initials: M
authors.lastname: Willicombe
authors.affiliation: Electron Microscopy Unit, Department of Histopathology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, United Kingdom; and.
authors.forename: Jill
authors.initials: J
authors.lastname: Moss
authors.affiliation: Electron Microscopy Unit, Department of Histopathology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, United Kingdom; and.
authors.forename: Linda
authors.initials: L
authors.lastname: Moran
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, Hammersmith Hospital, and.
authors.forename: Paul
authors.initials: P
authors.lastname: Brookes
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, Hammersmith Hospital, and.
authors.forename: Eva
authors.initials: E
authors.lastname: Santos-Nunez
authors.affiliation: Imperial College Renal and Transplant Centre.
authors.forename: Adam G
authors.initials: AG
authors.lastname: McLean
authors.affiliation: Imperial College Renal and Transplant Centre.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cairns
authors.affiliation: Imperial College Renal and Transplant Centre.
authors.forename: David
authors.initials: D
authors.lastname: Taube
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College Hammersmith Campus, London, United Kingdom Department of Cellular Pathology, Imperial College Healthcare National Health Service Trust, London, United Kingdom;
authors.forename: Terence H
authors.initials: TH
authors.lastname: Cook
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College Hammersmith Campus, London, United Kingdom Department of Cellular Pathology, Imperial College Healthcare National Health Service Trust, London, United Kingdom;
authors.forename: Candice
authors.initials: C
authors.lastname: Roufosse
mesh_terms: D000906:Antibodies; D042783:Endothelial Cells; D005260:Female; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014019:Tissue Donors; D014777:Virus Diseases / Q000473:pathology*
chemical_list: D000906:Antibodies
keywords: immunology and pathology; kidney transplantation; rejection; transplant outcomes; transplant pathology