title: Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss.
abstract: Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.
authors: Transplant Immunology Research Laboratory at Clinical Nephrology Unit, Department of Internal Medicine (DIMI), University of Genova, Genova, Italy.
authors: A
authors: A
authors: Nocera
authors: Transplant Immunology Research Laboratory at Clinical Nephrology Unit, Department of Internal Medicine (DIMI), University of Genova, Genova, Italy.
authors: A
authors: A
authors: Tagliamacco
authors: Nephrology, Dialysis and Transplantation Unit, G. Gaslini Institute, Genova, Italy.
authors: M
authors: M
authors: Cioni
authors: Transplantation Immunology, Fondazione Cà Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors: A
authors: A
authors: Innocente
authors: Kidney Transplant Surgery Unit, IRCCS Azienda Ospedaliera Universitaria S. Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors: I
authors: I
authors: Fontana
authors: Nephrology, Dialysis and Transplantation Unit, G. Gaslini Institute, Genova, Italy.
authors: G
authors: G
authors: Barbano
authors: Nephrology, Dialysis and Transplantation Unit, G. Gaslini Institute, Genova, Italy.
authors: A
authors: A
authors: Carrea
authors: Transplantation Immunology, Fondazione Cà Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors: M
authors: M
authors: Ramondetta
authors: Pathology Unit, Istituto G. Gaslini, Genova, Italy.
authors: A
authors: A
authors: Sementa
authors: Pediatric Hematology/Oncology, Fondazione Policlinico S. Matteo, Pavia, Italy.
authors: S
authors: S
authors: Basso
authors: Pediatric Hematology/Oncology, Fondazione Policlinico S. Matteo, Pavia, Italy.
authors: G
authors: G
authors: Quartuccio
authors: Biometry and Statistics Service, Fondazione Policlinico S. Matteo, Pavia, Italy.
authors: C
authors: C
authors: Klersy
authors: Kidney Transplant Surgery Unit, IRCCS Azienda Ospedaliera Universitaria S. Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors: M
authors: M
authors: Bertocchi
authors: Nephrology, Dialysis and Transplantation Unit, G. Gaslini Institute, Genova, Italy.
authors: E
authors: E
authors: Verrina
authors: Nephrology Unit, Department of Internal Medicine, University of Genova, Genova, Italy.
authors: G
authors: G
authors: Garibotto
authors: Nephrology, Dialysis and Transplantation Unit, G. Gaslini Institute, Genova, Italy.
authors: G M
authors: GM
authors: Ghiggeri
authors: Transplantation Immunology, Fondazione Cà Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors: M
authors: M
authors: Cardillo
authors: Pediatric Hematology/Oncology, Fondazione Policlinico S. Matteo, Pavia, Italy.
authors: P
authors: P
authors: Comoli
authors: Nephrology, Dialysis and Transplantation Unit, G. Gaslini Institute, Genova, Italy.
authors: F
authors: F
authors: Ginevri
mesh_terms: D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity; D002648:Child; D002675:Child, Preschool; D015922:Complement C1q / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007223:Infant; D007518:Isoantibodies / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000601:surgery; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D015922:Complement C1q
keywords: alloantibody; biomarker; biopsy; clinical research/practice; kidney transplantation/nephrology; monitoring: immune; pediatrics; rejection: antibody-mediated (ABMR)