Recurrence of bile salt export pump deficiency after liver transplantation.
Severe bile salt export pump (BSEP) deficiency is a hereditary cholestatic condition that starts in infancy and leads to end-stage liver disease. Three children who underwent orthotopic liver transplantation for severe BSEP deficiency had post-transplantation episodes of cholestatic dysfunction that mimicked the original disease. Remission of all episodes was achieved by intensifying the immunosuppressive regimen. The phenotypic recurrence of the disease correlated with the presence of circulating high-titer antibodies against BSEP that inhibit transport by BSEP in vitro. When administered to rats, these antibodies targeted the bile canaliculi and impaired bile acid secretion.
Pediatric Liver Service, La Paz University Hospital, Madrid, Spain.
Paloma
P
Jara
Loreto
L
Hierro
Pilar
P
Martínez-Fernández
Rita
R
Alvarez-Doforno
Francisca
F
Yánez
María C
MC
Diaz
Carmen
C
Camarena
Angela
A
De la Vega
Esteban
E
Frauca
Gema
G
Muñoz-Bartolo
Manuel
M
López-Santamaría
Javier
J
Larrauri
Luis
L
Alvarez
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001647:Bile Acids and Salts / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D002675:Child, Preschool; D002779:Cholestasis / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007565:Jaundice / Q000209:etiology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000276:immunology; D010641:Phenotype; D011537:Pruritus / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012074:Remission Induction; D017422:Sequence Analysis, DNA
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001323:Autoantibodies; D001647:Bile Acids and Salts; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C093491:ABCB11 protein, human