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 Symbiotic upcycling: Turning “low value” compounds into biomass
25.06.2019 | Max-Planck-Institut für Marine Mikrobiologie

nachricht New Therapy Promotes Vascular Repair Following Stroke
25.06.2019 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fraunhofer IDMT demonstrates its method for acoustic quality inspection at »Sensor+Test 2019« in Nürnberg

From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.

Reducing machine downtime, manufacturing defects, and excessive scrap

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Cooling with the sun

25.06.2019 | Power and Electrical Engineering

Robocabs: The mobility of the future?

25.06.2019 | Studies and Analyses

Skipping Meat on Occasion May Protect Against Type 2 Diabetes

25.06.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>