Autoimmune, Cholestatic and Biliary Disease
De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: A novel mechanism of cholestasis†
Article first published online: 20 MAY 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 50, Issue 2, pages 510–517, August 2009
How to Cite
Keitel, V., Burdelski, M., Vojnisek, Z., Schmitt, L., Häussinger, D. and Kubitz, R. (2009), De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: A novel mechanism of cholestasis. Hepatology, 50: 510–517. doi: 10.1002/hep.23083
Potential conflict of interest: Nothing to report.
- Issue published online: 29 JUL 2009
- Article first published online: 20 MAY 2009
- Accepted manuscript online: 20 MAY 2009 12:00AM EST
- Manuscript Accepted: 22 MAR 2009
- Manuscript Received: 15 SEP 2008
- German Research Foundation through the Collaborative Research Center “Experimental Hepatology”. Grant Number: SFB 575
Additional Supporting Information may be found in the online version of this article.
|HEP_23083_sm_SupFig1.tif||22655K||Supporting Figure 1: Localization of BSEP in the patient's transplanted livers. Biopsies from the patient's livers 2 (A) and 3 (B) were stained for BSEP in red and MRP2 in green. Both proteins co-localized in the canalicular membrane resulting in a yellow colouring. Bars = 10 μm.|
|HEP_23083_sm_SupFig2.tif||22655K||Supporting Figure 2: Immunohistological localization of BSEP and the tight junction protein ZO-1 in the patient's liver. BSEP and ZO-1 were co-stained in biopsies from the patient's liver (A, B) and a control liver. The tight junction complex delineates the canalicular from the basolateral membrane of hepatocytes. In control livers (C) the BSEP staining (red) is predominantly detected between the linear ZO-1 staining (green) of the tight junction complex. The same staining pattern was observed in biopsies from the patient's liver (A, B), indicating that BSEP is mainly localized within the canalicular membrane. Bars = 10 μm.|
|HEP_23083_sm_SupFig3.tif||22655K||Supporting Figure 3: Effects of mutations on the expression and localization of BSEP. Human BSEP was cloned and tagged to the yellow fluorescent protein (YFP) and expressed in HEK293 cells. (A) Wild-type BSEP-YFP is localized in the plasma membrane of transfected HEK293 cells. (B) Introduction of the V444A mutation did not alter the membrane localization of BSEPV444A-YFP. (C) The Y818F missense mutation did not affect the localization of BSEPY818F-YFP. (D) The combination of V444A and Y818F had no effect on the membrane localization of mutated BSEP. (E) Introduction of the G982R mutation caused retention of BSEPG982R-YFP in the endoplasmic reticulum. (F) Combination of V444A with G982R led to the localization of the mutated protein in the endoplasmic reticulum. (G) The combination of Y818F with G982R caused localization of the mutated protein in the endoplasmic reticulum. (H) Introduction of the patient's mutations (V444A, Y818F, G982R) caused the complete absence of the mutated protein. Bars=10 μm.|
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