Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Small difference, significant effect: How antibodies influence the defense against infections

06.08.2018

Some autoimmune diseases are successfully treated with monoclonal antibodies (mabs) targeted at inhibiting the release of the inflammatory messenger substance (cytokine) tumor necrosis factor alpha (TNFα). However, TNFα is also important for the defense against pathogenic agents. Researchers at PEI have compared the effects of various mabs for their ability of human immune cells to combat the parasite leishmania. Even a small molecular change (PEGylation) turned out to improve the immune defense against pathogens significantly. The results are reported in Frontiers in Immunology in its online version of 31 July 2018.

Autoimmune diseases are chronic inflammatory diseases in which immune cells erroneously attack the body’s own cells or tissue. In these diseases which, for example, also include rheumatoid arthritis, psoriasis, or chronic inflammatory diseases of the intestine such as Crohn’s disease, TNFα plays an important role. Among other things, it conveys the classic inflammatory symptoms: swelling, redness, and pain.


Monoclonal antibodies (mabs) against TNFα influence the defense against a leishmania infection at different rates.

Source: PEI

However, TNFα is a versatile cytokine which, in its role as a central regulator of the immune system is also important for the defense of pathogenic agents. Thus, there is evidence that the treatment with mabs blocking TNFα involves an increased risk of infectious disease. However, the data obtained up to now are contradictory.

Furthermore, an increased occurrence of the parasitic disease leishmaniosis was reported in patients treated with a particular mab. Leishmaniosis is caused by the single-cell parasite leishmanial transmitted by sand flies. The disease above all occurs in the Mediterranean, tropical regions, and Asia. Around one million people contract the disease world-wide each year.

Do TNFα-blocking mabs differ in their influence on the immune defense of the body? Researchers led by Professor Ger van Zandbergen, head of Division Immunology of the Paul Ehrlich Institut and Dr Katharina Arens have studied the influence of various TNFα-blocking mabs on the immune response of human immune cells against leishmania. The studies were performed by the researchers in vitro – outside the body.

For this purpose, they infected macrophages, certain immune cells of the body which are preferably infected by leishmainia, with the parasite. Then they added different mabs and T-lymphocytes. T-lymphocytes, in their role as important immune cells, are normally able to recognise infected macrophages, to replicate as a result of this contact, and to combat the pathogen directly.

The reactions of the T-cells to the parasite in the presence of the different mabs differed greatly. While some mabs markedly reduced T-lymphocyte activity thus enabling the parasites to replicate, the effect was lower with another mab – and replication of the leishmania was prevented.

In a next step, the researchers of the PEI compared the molecular structure of the mab showing the different action profiles. In doing so, they found that polymer polyethylene glycol (PEG) was the molecule that causes a small but significant difference. It primarily extends the half-life of the effect created by the antibody, since it protects from the body’s own digestion of the antibody: PEGylation – the adherence of the PEG to the mab at defined sites reduces the inhibitory effect of TNFα-blocking mabs on the immune defense against leishmanial.

The researchers conclude from these results that only small PEG modifications of TNFα inhibiting mabs are able to reduce effects that weaken the immune defense. In the researcher’s view, the differences between the mabs with regard to immune defense should be further studied in order to gain insights on the road to effective and even safer medicinal products.

The Paul-Ehrlich-Institut, the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main is a senior federal authority reporting to the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG). It is responsible for the research, assessment, and marketing authorisation of biomedicines for human use and immunological veterinary medicinal products.

Its remit also includes the authorisation of clinical trials and pharmacovigilance, i.e. recording and evaluation of potential adverse effects. Other duties of the institute include official batch control, scientific advice and inspections. In-house experimental research in the field of biomedicines and life science form an indispensable basis for the manifold tasks performed at the institute.

The Paul-Ehrlich-Institut, with its roughly 800 members of staff, also has advisory functions nationally (federal government, federal states (Länder)), and internationally (World Health Organisation, European Medicines Agency, European Commission, Council of Europe etc.).

Originalpublikation:

Original publication: Arens K, Filippis C, Kleinfelder H, Goetzee A, Crauwels P, Reichmann G, Waibler Z, Bagola K, van Zandbergen, G (2018): Anti‐TNFα therapeutics differentially affect Leishmania infection of human macrophages. Front. Immunol., 31 July 2018 |
https://doi.org/10.3389/fimmu.2018.01772

Weitere Informationen:

https://www.frontiersin.org/articles/10.3389/fimmu.2018.01772/full - Text of the Publication
https://www.pei.de/EN/information/journalists-press/press-releases/2018/14-small... - This press release on the PEI-Websiste

Dr. Susanne Stöcker | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Mapping the inner workings of a living cell
06.08.2018 | Columbia University

nachricht Aggressive tumors - New regulator in breast cancer cells discovered
06.08.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Concepts for new switchable plasmonic nanodivices

A magneto-plasmonic nanoscale router and a high-contrast magneto-plasmonic disk modulator controlled by external magnetic fields

Plasmonic waveguides open the possibility to develop dramatically miniaturized optical devices and provide a promising route towards the next-generation of...

Im Focus: 26AlF – the first detection of a radioactive molecule in space

The first unambiguous observation of a radioactive molecule, 26AlF, was made in the ancient nova-like object CK Vul (or Nova Vul 1670), which - most likely - is a stellar-merger remnant. The eruption of the object was observed between 1670-1672 in Europe. The interest in this object has been recently rejuvenated by the discovery of molecular gas of a very peculiar isotopic composition in the remnant.
The finding was announced by an international research team led by Tomasz Kamiński (CfA), including Karl Menten (MPIfR Bonn).

The variable star CK Vulpeculae (CK Vul) is known as the location of a stellar outbreak, a nova, which was observed by European astronomers in the 17th century...

Im Focus: Scientists create 'impossible' materials in simple way

Scientists from NUST MISIS and colleagues from the University of Bayreuth, the University of Münster (Germany), the University of Chicago (U.S.), and Linköping University (Sweden) have created nitrides, a material previously considered impossible to obtain. More amazing, they have shown that the material can be obtained using a very simple method of direct synthesis. Articles about the revolutionary research results have been published in Nature Communications and Angewandte Chemie International Edition.

Nitrides are actively used in superhard coatings and electronics. Usually, the nitrogen content in these materials is low, and it is therefore difficult to get...

Im Focus: World-first quantum computer simulation of chemical bonds using trapped ions

An international group of researchers has achieved the world’s first multi-qubit demonstration of a quantum chemistry calculation performed on a system of trapped ions, one of the leading hardware platforms in the race to develop a universal quantum computer.

The research, led by Cornelius Hempel and Thomas Monz, explores a promising pathway for developing effective ways to model chemical bonds and reactions using...

Im Focus: Growing brain cancer in a dish

For the first-time, researchers at IMBA- Institute of Molecular Biotechnology of the Austrian Academy of Sciences – develop organoids, that mimic the onset of brain cancer. This method not only sheds light on the complex biology of human brain tumors but could also pave the way for new medical applications.

Brain tumors are among the most aggressive and deadly cancers and a leading cause of cancer-related death in children and young adults.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

 
Latest News

High-resolution imaging of nanoparticle surface structures is now possible

06.08.2018 | Life Sciences

Mapping the inner workings of a living cell

06.08.2018 | Life Sciences

A periodic table of molecular knots

06.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>