Use of albumin isoforms profiles for the characterization of the etiology and severity of liver injuries

The inventors hypothesized that each type of liver injury can be revealed by a specific profile of HSA posttranslational modifications. Therefore, the aim of inventors was to study the pattern of albumin isoforms in rats intoxicated with acetaminophen (APAP), ethanol, and CCl4. The second objective was to explore the potential of these isoforms as biomarkers of liver specific injuries. The results demonstrate that albumin posttranslational modifications (Alb-PTM) occur very early during the course of liver injuries induced by hepatotoxic substances. In 3 animal models, native albumin started to decrease in favor of other isoforms 24 hours after the administration of APAP, ethanol or CCl4. Interestingly, the nature and the intensity of isoforms were different depending on the hepatotoxic substance. In a cohort of cirrhotic patients, the inventors were able to identify up to 14 albumin isoforms, all of which were also present in control patients. However, the inventors observed that the increase in the HSA-DA isoform was specific to patients with cirrhosis due to alcohol abuse, HSA+SGGS and HSA+2Glyc were increased specifically in NASH patients, and HSA-DA+Cys with HSA+SO2H were increased only in patients with the mixed form. In addition, we did not observe a specific isoform able to clearly discriminate the different stages of liver disease, but principal component analysis of the MS dataset perfectly separated cirrhosis patients with different Child-Pugh scores and control patients. The present invention thus relates to the use of albumin isoforms profiles for the characterization of the etiology and severity of liver injuries.

Keywords: Liver Injuries, Liver Transplant, NASH, MASH, Mass spectrometry
Patent Application number: European Procedure (Patents) (EPA) - 07 Oct. 2022 - 22 306 513.7
PCT/EP2023/077721 on 06/10/2023
Inventors:
EL BALKHI SouleimanSAINT-MARCOUX FranckSAUVAGE François-LudovicRAHALI Mohamed-AliMARQUET Pierre

Reference:

BIO22116-D1

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Patent filling date: 2022-10-07

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