title: Impacts of donor-specific anti-HLA antibodies and antibody-mediated rejection on outcomes after intestinal transplantation in children.
abstract: AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre-Tx period and de novo post-Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow-up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx.
authors.affiliation: Unité d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpitaux Universitaires de Genève, Geneve, Switzerland.
authors.forename: L-M
authors.initials: LM
authors.lastname: Petit
authors.affiliation: Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Rabant
authors.affiliation: Service d'Anatomopathologie, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Canioni
authors.affiliation: Laboratoire d'Histocompatibilité, Hôpital Saint Louis, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Suberbielle-Boissel
authors.affiliation: Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Goulet
authors.affiliation: Service de Chirurgie Viscérale Pédiatrique, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Chardot
authors.affiliation: Service d'Hépato-Gastroentérologie et Nutrition Pédiatriques, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Lacaille
mesh_terms: D000293:Adolescent; D000906:Antibodies / Q000276:immunology*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000069286:Bortezomib / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015935:Complement C4b / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D007223:Infant; D007422:Intestines / Q000637:transplantation*; D007518:Isoantibodies / Q000276:immunology; D008297:Male; D010446:Peptide Fragments / Q000276:immunology; D010956:Plasmapheresis; D011379:Prognosis; D000069283:Rituximab / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use; D014019:Tissue Donors; D014180:Transplantation; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D010446:Peptide Fragments; D013256:Steroids; D000069283:Rituximab; D000069286:Bortezomib; D015935:Complement C4b; C032261:complement C4d; C481642:eculizumab
keywords: antibody-mediated rejection; donor-specific antibodies; intestinal transplantation; long-term graft survival; steroid-resistant rejection