title: Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection.
abstract: The emerging role of humoral immunity in the pathogenesis of chronic allograft damage has prompted research aimed at assessing the role of anti-HLA antibody (Ab) monitoring as a tool to predict allograft outcome. Data on the natural history of allografts in children developing de novo Ab after transplantation are limited. Utilizing sera collected pretransplant, and serially posttransplant, we retrospectively evaluated 82 consecutive primary pediatric kidney recipients, without pretransplant donor-specific antibodies (DSA), for de novo Ab occurrence, and compared results with clinical-pathologic data. At 4.3-year follow up, 19 patients (23%) developed de novo DSA whereas 24 had de novo non-DSA (NDSA, 29%). DSA appeared at a median time of 24 months after transplantation and were mostly directed to HLA-DQ antigens. Among the 82 patients, eight developed late/chronic active C4d+ antibody-mediated rejection (AMR), and four C4d-negative AMR. Late AMR correlated with DSA (p < 0.01), whose development preceded AMR by 1-year median time. Patients with DSA had a median serum creatinine of 1.44 mg/dL at follow up, significantly higher than NDSA and Ab-negative patients (p < 0.005). In our pediatric cohort, DSA identify patients at risk of renal dysfunction, AMR and graft loss; treatment started at Ab emergence might prevent AMR occurrence and/or progression to graft failure.
authors.affiliation: Pediatric Nephrology, Istituto G. Gaslini, Genova, Italy. fabrizioginevri@ospedale-gaslini.ge.it
authors.forename: F
authors.initials: F
authors.lastname: Ginevri
authors.forename: A
authors.initials: A
authors.lastname: Nocera
authors.forename: P
authors.initials: P
authors.lastname: Comoli
authors.forename: A
authors.initials: A
authors.lastname: Innocente
authors.forename: M
authors.initials: M
authors.lastname: Cioni
authors.forename: A
authors.initials: A
authors.lastname: Parodi
authors.forename: I
authors.initials: I
authors.lastname: Fontana
authors.forename: A
authors.initials: A
authors.lastname: Magnasco
authors.forename: A
authors.initials: A
authors.lastname: Nocco
authors.forename: A
authors.initials: A
authors.lastname: Tagliamacco
authors.forename: A
authors.initials: A
authors.lastname: Sementa
authors.forename: P
authors.initials: P
authors.lastname: Ceriolo
authors.forename: L
authors.initials: L
authors.lastname: Ghio
authors.forename: M
authors.initials: M
authors.lastname: Zecca
authors.forename: M
authors.initials: M
authors.lastname: Cardillo
authors.forename: G
authors.initials: G
authors.lastname: Garibotto
authors.forename: G M
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: F
authors.initials: F
authors.lastname: Poli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007223:Infant; D007518:Isoantibodies / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012307:Risk Factors; D013997:Time Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies