Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

'Wimpy' antibody protects against kidney disease in mice

03.11.2014

An antibody abundant in mice and previously thought to offer poor assistance in fighting against infection may actually play a key role in keeping immune responses in check and preventing more serious self-inflicted forms of kidney disease, researchers say.

Led by researchers at the University of Cincinnati (UC) and Cincinnati Children's Hospital Medical Center and published online Nov. 2, 2014, in the journal Nature, the study finds that the mouse antibody IgG1, which is made in large quantities and resembles a human antibody known as IgG4, may actually be protective.

"Antibodies protect against pathogens, in large part, by clumping them together and by activating other defenses, including a set of serum proteins, known as complement, and cells that have antibody-binding molecules on their surface called Fc receptors," says Fred Finkelman, MD, Walter A. and George McDonald Foundation Chair of Medicine and professor of medicine and pediatrics at UC.

Finkelman is also an immunobiology researcher at Cincinnati Children's Hospital Medical Center. Richard Strait, MD, an assistant professor of pediatrics at UC and an attending physician at Cincinnati Children's, is the first author of the research published in Nature.

"Surprisingly, most of the antibody made by mice is IgG1, which is relatively defective in its ability to clump pathogens, activate complement, and activate cells by binding to their Fc receptors," says Finkelman, also a physician at the Cincinnati Department of Veterans Affairs (VA) Medical Center. "Humans have a similar type of antibody, called IgG4, which is also relatively defective in these abilities.

"Why should you have such a wimpy antibody? It's the antibody made in the largest amount. Our thought was that in biology, you don't get anything for free," says Finkelman. "If an antibody can kill bacteria and viruses very well, it might also cause inflammation that can harm the animal that makes it. So maybe you need some of these wimpy antibodies to protect against that type of self-inflicted damage."

Researchers tested their hypothesis by studying what happens when genetically bred mice that cannot make IgG1 are injected with a foreign protein that would spur a normal mouse's immune system to produce IgG1. The genetically bred mouse instead produced another antibody known as IgG3, which affected capillaries in the kidneys and ultimately led to renal failure.

"The mouse's kidneys turned yellow because they essentially shut off blood flow and within a few days there was total destruction of the filtering part of the kidney called the glomerulus," explains Finkelman.

However, injecting IgG1 into mice that could not make the antibody prevented them from developing kidney disease, says Finkelman.

"These findings support our hypothesis about the reason for making antibodies such as mouse IgG1 and human IgG4," says Finkelman. "They also demonstrate a new type of kidney disease that can be caused by certain types of antibody, such as mouse IgG3, even without complement or Fc receptors. In addition, our findings suggest that antibodies such as human IgG4 might be useful for treating people who have diseases caused by other types of antibody."

These diseases include myasthenia gravis and blistering skin diseases, says Finkelman.

Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. Individuals with the ailment lose the ability to contract their muscles because their body produces an antibody that destroys acetylcholine receptors in muscle.

"The nerves in their muscles continue to fire and they release the chemical acetylcholine, but there is not much for the acetylcholine to bind to," says Finkelman. "These people become very weak and can actually die because they can no longer swallow well or breathe well."

Individuals with blistering skin diseases make antibodies against the molecules that hold skin cells together, says Finkelman. As a result, the skin cells separate from each other, forming blisters.

"People can lose a lot of fluid and can get infected very easily," says Finkelman. "These are very serious diseases and the treatment is not very good."

Funding for this study came from a U.S. Department of Veterans Affairs Merit Award, the National Institutes of Health (R01 A1072040), the University of Cincinnati and Cincinnati Children's Hospital Medical Center.

Co-authors include; Ashley Mahler, Nathaniel Barasa, Jörg Köhl, MD; Keith Stringer, MD; Shiva Kumar Shanmukhappa, DVM, PhD; David Witte, MD; Md Monir Hossain, PhD; Marat Khoudou; PhD; and Andrew Herr, PhD; all affiliated with the University of Cincinnati and/or Cincinnati Children's; Chaim Jacob, MD, PhD, University of Southern California School of Medicine; and Marc Ehlers, University of Lübeck, Germany. Köhl is also affiliated with the University of Lübeck, Germany. Monica Posgai, PhD, is a recent postdoctoral fellow at the University of Cincinnati.

Cedric Ricks | EurekAlert!
Further information:
http://www.uc.edu

Further reports about: Health Veterans acetylcholine activate diseases kidney disease muscles skin skin cells

More articles from Life Sciences:

nachricht How our cellular antennas are formed
22.01.2019 | Université de Genève

nachricht Bifacial Stem Cells Produce Wood and Bast
22.01.2019 | Universität Heidelberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Bifacial Stem Cells Produce Wood and Bast

Heidelberg researchers study one of the most important growth processes on Earth

So-called bifacial stem cells are responsible for one of the most critical growth processes on Earth – the formation of wood.

Im Focus: Energizing the immune system to eat cancer

Abramson Cancer Center study identifies method of priming macrophages to boost anti-tumor response

Immune cells called macrophages are supposed to serve and protect, but cancer has found ways to put them to sleep. Now researchers at the Abramson Cancer...

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

How our cellular antennas are formed

22.01.2019 | Life Sciences

Proposed engineering method could help make buildings and bridges safer

22.01.2019 | Architecture and Construction

Bifacial Stem Cells Produce Wood and Bast

22.01.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>