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-...
Saved in:
Published in | Nephrology, dialysis, transplantation Vol. 35; no. Supplement_3 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford University Press
01.06.2020
|
Online Access | Get full text |
Cover
Loading…
Summary: | 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: |
---|---|
ISSN: | 0931-0509 1460-2385 |
DOI: | 10.1093/ndt/gfaa142.P0349 |