Proteins in drug-induced liver injuries

Maria Mikus - first author of the study
Immunohistochemistry analysis using anti-FABP1 and anti- CDH5 antibodies showed cytoplasmic expression patterns in liver and kidney.

Last week, researchers from the Human Protein Atlas, together with others, published a study on drug-induced liver injury in the journal Liver International.

Drug-induced liver injury is the single leading cause for termination of drug development and safety-related withdrawal of approved drugs from the market. In clinical practice, it accounts for more than 50% of liver failure cases and represents a major safety issue for patients. In some patients, drug-induced liver injury can cause severe injury leading to acute liver failure that can be life threatening and require liver transplantation.

Maria Mikus is the first author of the study, and a PhD student working in the “Biobank profiling - Affinity proteomics“ group at SciLifeLab.

– Our research aims to provide increased understanding of disease mechanisms as well as to identify biomarkers that can be used in for example diagnosis or prediction of disease. We use different microarray formats in combination with antibodies and antigens from the Human Protein Atlas to profile protein levels or presence of autoantibodies in different body fluids. My focus is in toxicology, inflammation and allergy.

In the present study Maria Mikus and her co-workers performed a multi-cohort profiling of 241 individuals and more than 1000 samples in the context of drug-induced liver injury.

– We found increased levels of cadherin-5 (CDH5) and fatty acid-binding protein 1 (FABP1) in individuals developing liver injury after exposure to a variety of drugs compared to controls.

The proteins showed interesting characteristics that may be useful in prediction or diagnosis. In the longitudinal cohorts, CDH5 was elevated at baseline and may therefore have a potential as a susceptibility marker. FABP1 was elevated after treatment initiation and has in addition a favourable tissue distribution compared to for example the clinically used marker alanine aminotransferase.

– We hope that these candidate markers will find use in the clinic as well as in drug-development. The next step is to continue to verify and validate the importance of these proteins and try to understand their role, Maria Mikus concludes.

Read the whole study in Liver International

Explore the proteins CDH5 and FABP1 in the Human Protein Atlas.

Frida Henningson Johnson