title: DQ molecules are the principal stimulators of de novo donor-specific antibodies in nonsensitized pediatric recipients receiving a first kidney transplant.
abstract: Data on the different HLA-antibody (Ab) categories in pediatric kidney recipients developing de novo donor-specific Abs (DSA) after transplantation are scarce. We retrospectively evaluated 82 consecutive nonsensitized pediatric recipients of a first kidney graft for de novo HLA Ab occurrence and antigen specificity. At a median follow-up of 6 years, 29% of patients developed de novo DSA, while 45% had de novo non-DSA. DSA appeared at 25-month median time post-transplant and were mostly directed toward HLA-DQ antigens. Considering each HLA antigen, the estimated rate of DQ DSA (7.55 per 100 person-years) was much higher than the rates observed for non-DQ DSA. The HLA-DQ Ab recognized determinants of the DQβ chain in 70% of cases, α chain in 25% of cases, and both chains in one patient. Non-DSA peaked earlier than DSA, and were largely directed against HLA class I specificities that belonged to HLA-A- and HLA-B-related cross-reacting epitope groups (CREG) in 56% of cases. Our results indicate a need for evaluating HLA-DQ compatibilities in kidney allocation, in order to minimize post-transplant development of de novo DSA, known to be responsible for antibody-mediated rejection and graft loss.
authors.affiliation: Transplant Immunology Research Laboratory at Clinical Nephrology and Gastroenterology Units, Department of Internal Medicine -DIMI, University of Genova, Genova, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Tagliamacco
authors.forename: Michela
authors.initials: M
authors.lastname: Cioni
authors.forename: Patrizia
authors.initials: P
authors.lastname: Comoli
authors.forename: Miriam
authors.initials: M
authors.lastname: Ramondetta
authors.forename: Caterina
authors.initials: C
authors.lastname: Brambilla
authors.forename: Antonella
authors.initials: A
authors.lastname: Trivelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Magnasco
authors.forename: Roberta
authors.initials: R
authors.lastname: Biticchi
authors.forename: Iris
authors.initials: I
authors.lastname: Fontana
authors.forename: Pietro
authors.initials: P
authors.lastname: Dulbecco
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ginevri
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardillo
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Nocera
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D012189:Retrospective Studies; D014019:Tissue Donors
chemical_list: D006683:HLA-DQ Antigens
keywords: Antibody-mediated rejection; HLA donor-specific antibodies; HLA matching; de novo HLA antibodies; pediatric kidney transplantation