title: Rituximab as therapy for the recurrence of bile salt export pump deficiency after liver transplantation.
abstract: Progressive familial intrahepatic cholestasis type 2 (PFIC2) results from recessive mutations in the adenosine triphosphate-binding cassette B11 gene, which encodes for bile salt export pump (BSEP). Liver transplantation (LT) is offered to PFIC2 patients with end-stage liver disease. Reports have described recurrent cholestasis in PFIC2 patients after transplantation, and this has been associated with immunoglobulin G antibodies to BSEP. High-titer anti-BSEP antibodies appear to correlate with episodes of cholestatic graft dysfunction. There is no established paradigm for treating antibody-mediated posttransplant BSEP disease. It appears to be refractory to changes in immunosuppressant medications that would typically be effective in treating allograft rejection. Taking what is known about its pathophysiology, we designed a treatment consisting of rituximab, a chimeric monoclonal anti-CD20 antibody, in combination with intravenous immunoglobulin and plasmapheresis. Using this approach, we report the successful management of 2 patients with antibody-mediated recurrence of PFIC2 after LT.
authors.affiliation: Departments of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Henry C
authors.initials: HC
authors.lastname: Lin
authors.forename: Luis
authors.initials: L
authors.lastname: Alvarez
authors.forename: Greggy
authors.initials: G
authors.lastname: Laroche
authors.forename: Hector
authors.initials: H
authors.lastname: Melin-Aldana
authors.forename: Kim
authors.initials: K
authors.lastname: Pfeifer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Schwarz
authors.forename: Peter F
authors.initials: PF
authors.lastname: Whitington
authors.forename: Estella M
authors.initials: EM
authors.lastname: Alonso
authors.forename: Udeme D
authors.initials: UD
authors.lastname: Ekong
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000906:Antibodies / Q000097:blood*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000601:surgery*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D016031:Liver Transplantation; D008297:Male; D010641:Phenotype; D010956:Plasmapheresis; D012008:Recurrence; D000069283:Rituximab; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D000906:Antibodies; D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D000069283:Rituximab