High affinity anti‐BSEP antibodies after liver transplantation for PFIC‐2 – Successful treatment with immunoadsorption and B‐cell depletion

• Published in: Pediatric transplantation Vol. 20; no. 7; pp. 987 - 993
• Main Authors: Kubitz, Ralf, Dröge, Carola, Kluge, Stefanie, Stindt, Jan, Stross, Claudia, Häussinger, Dieter, Flechtenmacher, Christa, Wenning, Daniel, Teufel, Ulrike, Schmitt, Claus Peter, Engelmann, Guido
• Format: Journal Article
• Language: English
• Published: Denmark 01.11.2016
• Subjects: ABCB11 gene; Adolescent; Antibodies - analysis; Antibodies - chemistry; Antigens, CD20 - immunology; ATP Binding Cassette Subfamily B Member 11; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - immunology; B-Lymphocytes - cytology; Biopsy; canalicular antibodies; children; Cholestasis, Intrahepatic - surgery; Epitopes - chemistry; Humans; Immunosuppression - adverse effects; Immunosuppressive Agents - therapeutic use; Liver Transplantation; Male; Mutation; PFIC recurrence; Phenotype; Recurrence; Remission Induction; rituximab; Rituximab - therapeutic use; canalicular antibodies; ABCB11 gene; children; rituximab; PFIC recurrence
• ISSN: 1397-3142; 1399-3046
• DOI: 10.1111/petr.12751

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.