Transplantation 2015 Jan;99(1):243-9
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.
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.
Conclusion: 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.