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!
Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
Identified the component that allows a lethal bacteria to spread resistance to antibiotics
27.07.2017 | Institute for Research in Biomedicine (IRB Barcelona)
Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.
Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...
Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers
Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...
Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.
At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
26.07.2017 | Event News
21.07.2017 | Event News
19.07.2017 | Event News
27.07.2017 | Life Sciences
27.07.2017 | Life Sciences
27.07.2017 | Health and Medicine