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MHH researchers discover molecular signatures, which could aid diagnosis.
Liver transplants often save the lives of seriously ill patients. However, there remains a risk that the body will reject the new organ. Doctors distinguish between acute and chronic rejection. While acute rejection is easy to diagnose and treat, chronic rejection causes lasting damage to the organ, is difficult to detect – currently only possible by examining tissue samples under a microscope – and is often overlooked. An international research team led by Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI) has now discovered clear molecular signatures for chronic rejection after liver transplantation, which could aid diagnosis. After ten years of work, the findings have now been published in the Journal of Hepatology.
Two types of rejection
‘Chronic and acute rejection differ in terms of cause, progression and treatment,’ explains first author Dr Bastian Engel, MHH-Clinical Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology (GHIE). ‘In chronic rejection, antibodies attack the blood vessels of the transplanted liver, often without noticeable liver values. Up to 50 percent of cases lead to scarring, which can cause cirrhosis of the liver and necessitate a repeat transplant. Doctors treat the condition using traditional immunosuppressants and measures to reduce antibodies, such as plasmapheresis, and high-dose immunoglobulin administration – with varying degrees of success.
Acute rejection is easier to recognise and treat. In the process, immune cells attack the donor liver, causing and elevated liver values. The risk of permanent scarring is lower, and acute rejection usually responds well to an adjustment of immunosuppression or temporary high-dose cortisone administration. ‘The crucial thing is that these two forms not only progress differently, but also exhibit their own molecular activity patterns – typical fingerprints in the organ. We have clearly distinguished these signatures from each other for the first time,’ explains doctoral student and physician Alejandro Campos-Murguia, also a first author from the gastroenterology department.
Different treatments – a major challenge
The team analysed for the first time which genes are active in tissue samples from liver transplant patients with and without acute and chronic rejection. The samples came from Hanover and Barcelona. ‘We analysed data from gene expression, cytokines, complement factors and the extracellular matrix (ECM) – i.e. from various molecules and structures that play a role in cells and tissue – in more than 158 samples,’ reports Ahmed Alaswad, doctoral student at the Centre for Individualised Infection Medicine (CiiM), a joint initiative of the HZI and the MHH, and first author. ‘Our analyses clearly show for the first time that signalling pathways leading to liver scarring, such as TNF–NF-κB signalling and complement activation, part of the innate immune system, indicate chronic rejection.’
Better diagnosis of rejection
The findings are more than just basic research. ‘In the future, these molecular signatures can help to diagnose chronic rejection in surveillance transplant biopsies earlier and more accurately, thus enabling more targeted treatment,’ says Prof. Dr. Richard Taubert, senior physician at the GHIE liver transplant outpatient clinic.
‘The results are an important step towards personalised medicine in transplant research,’ emphasises Prof. Dr. Yang Li, professor at MHH, co-director of the CiiM and head of the ‘Bioinformatics of Individualised Medicine’ research department at the HZI. ‘Our goal is for every patient to receive the best possible individualised therapy – so that they can live significantly longer with their transplanted organ.’
SERVICE
For further information, please contact Dr. Bastian Engel, Engel.Bastian@mh-hannover.de.
https://www.sciencedirect.com/science/article/pii/S0168827825023384?via%3Dihub
Discussing research results (from left): Ahmed Alaswad, Alejandro Campos-Murguia and Dr Bastian Enge ...
Copyright: Karin Kaiser/MHH.
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