P0349A MISSPROCESSED FORM OF APOLIPOPROTEIN A-I IS SPECIFICALLY ASSOCIATED TO RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS
Abstract Background and Aims Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation. There are no accurate means to diagnose the relapses or to detect the patients at risk. In an exploratory study we detected Apolipoprotein A-...
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Published in | Nephrology, dialysis, transplantation Vol. 35; no. Supplement_3 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford University Press
01.06.2020
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Online Access | Get full text |
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Abstract | Abstract
Background and Aims
Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation. There are no accurate means to diagnose the relapses or to detect the patients at risk. In an exploratory study we detected Apolipoprotein A-Ib (ApoA-Ib), a high molecular weight form of ApoA-I, specifically in urine of kidney transplanted patients that relapsed of FSGS. The diagnostic performance of ApoA-Ib has been assessed in two independent cohorts obtaining high specificity (94,1 %) and sensitivity (87,5 %) to detect FSGS relapses. It has also a potential to detect patients at risk of relapse as ApoA-Ib predates the recurrence episodes in most of the cases. As urinary ApoA-Ib is strongly associated to primary FSGS we aimed to unravel the nature of the modification present in ApoA-Ib.
Method
The whole APOA1 gene was sequenced in ApoA-Ib positive and negative patients and the protein structure was studied using 2D electrophoresis followed by mass spectrometry.
Results
No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in the molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I). These results suggest that proApoA-I is miss-cleaved producing ApoA-Ib probably due to an altered protease activity in recurrent FSGS patients
Conclusion
ApoA-Ib, found specifically in urine of recurrent FSGS patients, is a misprocessed form of ApoA-I that retains three aminoacids of the six-aminoacid N-terminal propeptide of proApoA-I. The description of ApoA-Ib could be relevant not only to allow the automated analysis of this biomarker in the clinical laboratory but also to shed light into the molecular mechanism of idiopathic FSGS.
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AbstractList | Abstract
Background and Aims
Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation. There are no accurate means to diagnose the relapses or to detect the patients at risk. In an exploratory study we detected Apolipoprotein A-Ib (ApoA-Ib), a high molecular weight form of ApoA-I, specifically in urine of kidney transplanted patients that relapsed of FSGS. The diagnostic performance of ApoA-Ib has been assessed in two independent cohorts obtaining high specificity (94,1 %) and sensitivity (87,5 %) to detect FSGS relapses. It has also a potential to detect patients at risk of relapse as ApoA-Ib predates the recurrence episodes in most of the cases. As urinary ApoA-Ib is strongly associated to primary FSGS we aimed to unravel the nature of the modification present in ApoA-Ib.
Method
The whole APOA1 gene was sequenced in ApoA-Ib positive and negative patients and the protein structure was studied using 2D electrophoresis followed by mass spectrometry.
Results
No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in the molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I). These results suggest that proApoA-I is miss-cleaved producing ApoA-Ib probably due to an altered protease activity in recurrent FSGS patients
Conclusion
ApoA-Ib, found specifically in urine of recurrent FSGS patients, is a misprocessed form of ApoA-I that retains three aminoacids of the six-aminoacid N-terminal propeptide of proApoA-I. The description of ApoA-Ib could be relevant not only to allow the automated analysis of this biomarker in the clinical laboratory but also to shed light into the molecular mechanism of idiopathic FSGS. Abstract Background and Aims Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation. There are no accurate means to diagnose the relapses or to detect the patients at risk. In an exploratory study we detected Apolipoprotein A-Ib (ApoA-Ib), a high molecular weight form of ApoA-I, specifically in urine of kidney transplanted patients that relapsed of FSGS. The diagnostic performance of ApoA-Ib has been assessed in two independent cohorts obtaining high specificity (94,1 %) and sensitivity (87,5 %) to detect FSGS relapses. It has also a potential to detect patients at risk of relapse as ApoA-Ib predates the recurrence episodes in most of the cases. As urinary ApoA-Ib is strongly associated to primary FSGS we aimed to unravel the nature of the modification present in ApoA-Ib. Method The whole APOA1 gene was sequenced in ApoA-Ib positive and negative patients and the protein structure was studied using 2D electrophoresis followed by mass spectrometry. Results No genetic variations in the APOA1 gene were found in the ApoA-Ib positive patients that could explain the increase in the molecular mass. The mass spectrometry analysis revealed three extra amino acids at the N-Terminal end of ApoA-Ib that were not present in the standard plasmatic form of ApoA-I. These amino acids corresponded to half of the propeptide sequence of the immature form of ApoA-I (proApoA-I). These results suggest that proApoA-I is miss-cleaved producing ApoA-Ib probably due to an altered protease activity in recurrent FSGS patients Conclusion ApoA-Ib, found specifically in urine of recurrent FSGS patients, is a misprocessed form of ApoA-I that retains three aminoacids of the six-aminoacid N-terminal propeptide of proApoA-I. The description of ApoA-Ib could be relevant not only to allow the automated analysis of this biomarker in the clinical laboratory but also to shed light into the molecular mechanism of idiopathic FSGS. Figure: |
Author | Puig Gay, Natàlia Helm, Dominic Seron Micas, Daniel Jacobs Cachá, Conxita Moreso, Francesc Sellares, Joana López Hellín, Joan Rettel, Mandy Savitski, Mikhail M Soler, María José Meseguer, Anna |
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Background and Aims
Recurrence of idiopathic FSGS, a glomerular disease of unknown aetiology, is a serious complication after kidney transplantation.... |
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Title | P0349A MISSPROCESSED FORM OF APOLIPOPROTEIN A-I IS SPECIFICALLY ASSOCIATED TO RECURRENT FOCAL SEGMENTAL GLOMERULOSCLEROSIS |
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