Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibodies as ‘messengers’ in the nervous system

27.01.2017

Antibodies are able to activate human nerve cells within milliseconds and hence modify their function — that is the surprising conclusion of a study carried out at Human Biology at the Technical University of Munich (TUM). This knowledge improves our understanding of illnesses that accompany certain types of cancer, above all severe intestinal malfunctions.

Functional disorders in organs that manifest in conjunction with tumors are called paraneoplastic syndromes. These syndromes are not caused by the primary tumor itself, but are instead frequently a result of the body’s autoimmune reaction. In such cases, a person’s own antibodies turn against their own cells and attack them.


A Ganglion in the human intestine, which shows nerval activity after giving the anti-HuD-serum. The activity is red.

(Fig.: Schemann, Michel/ TUM)

One of these functional disorders is paralysis of the intestinal tract, for example intestinal pseudoobstruction. It makes it difficult for patients to obtain the nutrients and calories they require from their diet. The so-called anti-Hu syndrome is a type of paraneoplastic syndrome often associated with atonic gut and generally occurs in conjunction with small-cell lung cancer. Paraneoplastic syndromes often occur before the tumor is even detected.

Hu proteins are usually located in the nucleus of all nerve cells and consist of four family members (HuA, B, C, and D). Because the tumor releases the Hu protein, the immune system generates antibodies to fight it. Initially, they serve to defend against the tumor: The greater the concentration of antibodies, the slower the tumor grows. However, these anti-Hu antibodies — named after the first patient in whom these antibodies were discovered in 1985 — also result in an autoimmune reaction with severe gut disorders as an accompanying illness.

Nerves are activated before they can be damaged

Professor Michael Schemann and his colleagues at the Chair for Human Biology at TUM wanted to identify causes for possible nervous function disorders that occur in paraneoplastic syndromes and paralytic intestine. For this purpose, they examined serums from patients with small-cell lung cancer from the Mayo Clinic in Rochester, MN (USA). In a study conducted over a period of ten years, the researchers were able to show for the first time that these patient serums activate human nerve cells within milliseconds without causing neuronal damage. This modifies nerve functions long before the autoimmune reaction damages the nerves.

Working together with the company Euroimmun from Lübeck, the team was even able to identify the factor responsible for this: Normally, nerve cells are activated or inhibited via neurotransmitters that bind to specific structures in the cell membrane (receptors). Surprisingly, it turned out to be an antibody — namely the anti-HuD antibody — which stimulated the nerve cells in the patient serums.

Antibody mimics neurotransmitters acetylcholine and adenosine triphosphate

What was striking about this finding was the fact that the antibody does not achieve this effect binding to its genuine target protein. “Interestingly, the nerve-activating effect is transmitted via receptors for neurotransmitters,” said Professor Schemann. “These receptors are usually activated by acetylcholine and adenosine triphosphate.” In a nutshell, the antibody more or less mimics the effects of the neurotransmitters acetylcholine and adenosine triphosphate.

The HuD protein typically stabilizes ribonucleic acid (RNA) and has nothing to do with nerve activation. How and where exactly the anti-HuD antibody binds to the receptors continues to remain a black box. However, this newly discovered effect of the anti-HuD-antibody heralds a paradigm shift, according to Professor Schemann, because antibodies are able to activate nerves regardless of antibody-specific binding structures on the cell membrane.

“Although what we have found will not heal lung cancer itself,” Professor Schemann explained, “it will lead to new clinical understanding and hence hopefully to new therapeutic approaches for related paraneoplastic syndromes such as intestinal pseudoobstruction.”

Just recently, the research group at the Chair for Human Biology, in collaboration with the Charité in Berlin, demonstrated that antibodies are able to activate human nerves*. In this case, the functional principle was obvious, as the binding of the antibody to defined structures of a potassium channel modified the excitability of the nerves.

Publications:
Qin Li**, Klaus Michel**, Anita Annahazi, Ihsan E. Demir, Güralp O. Ceyhan, Florian Zeller, Lars Komorowski, Winfried Stöcker, Michael J. Beyak, David Grundy, Gianrico Farrugia, Roberto De Giorgio und Michael Schemann: Anti-Hu antibodies activate enteric and sensory neurons, Scientific Reports 12/2016. (** coordinate 1st-authors)
DOI: 10.1038/srep38216
http://www.nature.com/articles/srep38216

*Piepgras J, Höltje M, Michel K, Li Q, Otto C, Drenckhahn C, Probst C, Schemann M, Jarius S, Stöcker W, Balint B, Meinck HM, Buchert R, Dalmau J, Ahnert-Hilger G, Ruprecht K.: Anti-DPPX encephalitis, Neurology 2015 Sep 8;85(10):890-7.
DOI: 10.1212/WNL.0000000000001907

Contact:

Prof. Dr. Michael Schemann
Technical University of Munich
Chair for Human Biology
Tel: +49/8161/71 5403
schemann@wzw.tum.de

Weitere Informationen:

https://www.tum.de/die-tum/aktuelles/pressemitteilungen/detail/article/33691/
http://humanbiology.wzw.tum.de/index.php?id=24&L=1

Dr. Ulrich Marsch | Technische Universität München

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>