title: High affinity anti-BSEP antibodies after liver transplantation for PFIC-2 - Successful treatment with immunoadsorption and B-cell depletion.
abstract: PFIC due to BSEP mutations (PFIC type 2) often necessitates OLT. It has recently been recognized that some PFIC-2 patients develop phenotypic disease recurrence post-OLT due to the appearance of anti-BSEP antibodies. Here, we describe a boy who became cholestatic four yr after OLT during modification of immunosuppression. Canalicular antibody deposits were detected in biopsies of the transplant and antibodies specifically reacting with BSEP were identified at high titers in his serum. These antibodies bound extracellular epitopes of BSEP and inhibited BS transport and were assumed to cause disease recurrence. Consequently, anti-BSEP antibody depletion was pursued by IA and B-cell depletion by anti-CD20 antibodies (rituximab) along with a switch of immunosuppression. This treatment resulted in prolonged relief of symptoms. Depletion of pathogenic anti-BSEP antibodies causing AIBD after OLT in PFIC-2 patients should be considered as a central therapeutic goal.
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kubitz
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Carola
authors.initials: C
authors.lastname: Dröge
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kluge
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Stindt
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Stross
authors.affiliation: Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.affiliation: Department of General Pathology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Christa
authors.initials: C
authors.lastname: Flechtenmacher
authors.affiliation: Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wenning
authors.affiliation: Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Teufel
authors.affiliation: Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany.
authors.forename: Claus Peter
authors.initials: CP
authors.lastname: Schmitt
authors.affiliation: Department of Paediatrics, Lukas Hospital, Neuss, Germany. engelmann@lukasneuss.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Engelmann
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000906:Antibodies / Q000032:analysis / Q000737:chemistry*; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology*; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000601:surgery*; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation; D008297:Male; D009154:Mutation; D010641:Phenotype; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab / Q000627:therapeutic use
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D000906:Antibodies; D018951:Antigens, CD20; D000939:Epitopes; D007166:Immunosuppressive Agents; D000069283:Rituximab
keywords: ABCB11 gene; PFIC recurrence; canalicular antibodies; children; rituximab