Autoimmune BSEP Disease: Disease Recurrence After Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

详细信息    查看全文

• 作者：Ralf Kubitz ; Carola Dr?ge ; Stefanie Kluge…
• 关键词：Autoimmune disease ; Autoreactive antibodies ; Bile salt export pump ; BSEP ; PFIC ; 2
• 刊名：Clinical Reviews in Allergy & Immunology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：48
• 期：2-3
• 页码：273-284
• 全文大小：638 KB
• 参考文献：1. Davit-Spraul, A, Gonzales, E, Baussan, C, Jacquemin, E (2009) Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis 4: pp. 1 CrossRef
  2. Strautnieks, SS, Byrne, JA, Pawlikowska, L (2008) Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology 134: pp. 1203-1214 CrossRef
  3. Aydogdu, S, Cakir, M, Arikan, C (2007) Liver transplantation for progressive familial intrahepatic cholestasis: clinical and histopathological findings, outcome and impact on growth. Pediatr Transplant 11: pp. 634-640 CrossRef
  4. Jacquemin, E (2000) Progressive familial intrahepatic cholestasis. Genetic basis and treatment. Clin Liver Dis 4: pp. 753-763 CrossRef
  5. Jacquemin, E (2012) Progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol 36: pp. S26-S35 CrossRef
  6. Paulusma, CC, Groen, A, Kunne, C (2006) Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport. Hepatology 44: pp. 195-204 CrossRef
  7. Bull, LN, Eijk, MJ, Pawlikowska, L (1998) A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet 18: pp. 219-224 CrossRef
  8. Strautnieks, SS, Bull, LN, Knisely, AS (1998) A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet 20: pp. 233-238 CrossRef
  9. Gerloff, T, Stieger, B, Hagenbuch, B (1998) The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J Biol Chem 273: pp. 10046-10050 CrossRef
  10. Kubitz, R, Dr?ge, C, Stindt, J, Weissenberger, K, H?ussinger, D (2012) The bile salt export pump (BSEP) in health and disease. Clin Res Hepatol Gastroenterol 36: pp. 536-553 CrossRef
  11. Davit-Spraul, A, Fabre, M, Branchereau, S (2010) ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history. Hepatology 51: pp. 1645-1655 CrossRef
  12. Morotti, RA, Suchy, FJ, Magid, MS (2011) Progressive familial intrahepatic cholestasis (PFIC) type 1, 2, and 3: a review of the liver pathology findings. Semin Liver Dis 31: pp. 3-10 CrossRef
  13. Knisely, AS, Strautnieks, SS, Meier, Y (2006) Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Hepatology 44: pp. 478-486 CrossRef
  14. Sheridan R.M., Gupta A., Miethke A., Knisely A.S. and Bove K.E. (2012) Multiple dysplastic liver nodules in PFIC2 underscore risk for neoplasia associated with functional BSEP deficiency. Am.J.Surg.Pathol
  15. Knisely, AS (2000) Progressive familial intrahepatic cholestasis: a personal perspective. Pediatr Dev Pathol 3: pp. 113-125 CrossRef
  16. Byrne, JA, Strautnieks, SS, Ihrke, G (2009) Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology 49: pp. 553-567 CrossRef
  17. Faust, TW (2000) Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and aut
• 刊物主题：Allergology; Immunology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-0267

文摘

Severe cholestasis may result in end-stage liver disease with the need of liver transplantation (LTX). In children, about 10?% of LTX are necessary because of cholestatic liver diseases. Apart from bile duct atresia, three types of progressive familial intrahepatic cholestasis (PFIC) are common causes of severe cholestasis in children. The three subtypes of PFIC are defined by the involved genes: PFIC-1, PFIC-2, and PFIC-3 are due to mutations of P-type ATPase ATP8B1 (familial intrahepatic cholestasis 1, FIC1), the ATP binding cassette transporter ABCB11 (bile salt export pump, BSEP), or ABCB4 (multidrug resistance protein 3, MDR3), respectively. All transporters are localized in the canalicular membrane of hepatocytes and together mediate bile salt and phospholipid transport. In some patients with PFIC-2 disease, recurrence has been observed after LTX, which mimics a PFIC phenotype. It could be shown by several groups that inhibitory anti-BSEP antibodies emerge, which most likely cause disease recurrence. The prevalence of severe BSEP mutations (e.g., splice site and premature stop codon mutations) is very high in this group of patients. These mutations often result in the complete absence of BSEP, which likely accounts for an insufficient auto-tolerance against BSEP. Although many aspects of this “new-disease are not fully elucidated, the possibility of anti-BSEP antibody formation has implications for the pre- and posttransplant management of PFIC-2 patients. This review will summarize the current knowledge including diagnosis, pathomechanisms, and management of “autoimmune BSEP disease.-/p>