title: Posttransplant soluble B-cell activating factor kinetics in pediatric recipients of first kidney allograft.
abstract: BACKGROUND
  Development of de novo donor-specific antibodies (dnDSA) is associated with late or chronic antibody-mediated rejection (CAMR) and poor graft outcome in low-risk kidney transplant recipients. High-level soluble B-cell activating factor (sBAFF) was observed in kidney recipients at higher risk of developing dnDSA.
  
  
  METHODS
  We longitudinally analyzed sBAFF levels in 81 consecutive primary pediatric kidney recipients monitored for de novo human leukocyte antigen (HLA) antibody (Ab) occurrence to gain insight into the events conditioning B-cell activation posttransplant and to analyze the usefulness of paired DSA-sBAFF monitoring in this clinical setting.
  
  
  RESULTS
  At a median follow-up of 65 months, 23 patients (28%) developed dnDSA, with 13 of 23 developing CAMR. Irrespective of HLA Ab status, sBAFF levels progressively increased in all patients in the first posttransplant year, thereafter reaching a plateau. sBAFF levels were influenced by the degree of HLA class I antigen match and donor age. Despite higher levels of sBAFF in HLA Ab-positive patients (median and 95% confidence interval sBAFF in DSA+non-DSA patients: 568, 534-608 pg/mL vs. 502, 422-548 pg/mL in Ab-negative patients; P<0.05), we found that sBAFF monitoring could not predict DSA development by a time to event longitudinal analysis. Moreover, sBAFF kinetics up to CAMR onset could not anticipate CAMR development in the DSA cohort.
  
  
  CONCLUSIONS
  Our findings provide evidence of early posttransplant B-cell activation even in unsensitized recipients of first kidney allograft. The significance of this activation, likely induced by exposition to the allograft, is yet unclear.
authors.affiliation: 1 Pediatric Hematology and Oncology, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy. 2 Pediatric Nephrology, IRCCS Istituto G. Gaslini, Genova, Italy. 3 Nephrology Unit, Ospedale Presidio di Sestri Levante, Italy. 4 Transplant Immunology, IRCCS Azienda Ospedaliera Universitaria S. Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 5 Department of Surgery, Kidney Transplantation Unit, IRCCS Azienda Ospedaliera Universitaria S. Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy. 6Transplantation Immunology, Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy. 7 Biometry and Clinical Epidemiology Service, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Quartuccio
authors.forename: Michela
authors.initials: M
authors.lastname: Cioni
authors.forename: Angelica
authors.initials: A
authors.lastname: Parodi
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Nocera
authors.forename: Sabrina
authors.initials: S
authors.lastname: Basso
authors.forename: Iris
authors.initials: I
authors.lastname: Fontana
authors.forename: Alberto
authors.initials: A
authors.lastname: Magnasco
authors.forename: Viviana
authors.initials: V
authors.lastname: Sioli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Guido
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardillo
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ginevri
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D053264:B-Cell Activating Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation; D007700:Kinetics; D008137:Longitudinal Studies; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; D006680:HLA Antigens; D007518:Isoantibodies; C505719:TNFSF13B protein, human