High affinity anti-BSEP antibodies after liver transplantation for PFIC-2 – Successful treatment with immunoadsorption and B-cell depletion
Ralf Kubitz
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorCarola Dröge
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorStefanie Kluge
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorJan Stindt
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorClaudia Stross
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorDieter Häussinger
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorChrista Flechtenmacher
Department of General Pathology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorDaniel Wenning
Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorUlrike Teufel
Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorClaus Peter Schmitt
Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Guido Engelmann
Department of Paediatrics, Lukas Hospital, Neuss, Germany
Guido Engelmann, MD, Department of Pediatrics, Lukas Hospital, Preussenstrasse 84, D-41464 Neuss, Germany
Tel.: +49 2131 888 3500
Fax: +49 2131 888 3599
E-mail: [email protected]
Search for more papers by this authorRalf Kubitz
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorCarola Dröge
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorStefanie Kluge
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorJan Stindt
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorClaudia Stross
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorDieter Häussinger
Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Search for more papers by this authorChrista Flechtenmacher
Department of General Pathology, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorDaniel Wenning
Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorUlrike Teufel
Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorClaus Peter Schmitt
Department of General Paediatrics, Centre for Paediatric and Adolescent Medicine, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorCorresponding Author
Guido Engelmann
Department of Paediatrics, Lukas Hospital, Neuss, Germany
Guido Engelmann, MD, Department of Pediatrics, Lukas Hospital, Preussenstrasse 84, D-41464 Neuss, Germany
Tel.: +49 2131 888 3500
Fax: +49 2131 888 3599
E-mail: [email protected]
Search for more papers by this authorAbstract
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.
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