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!
Researchers target protein that protects bacteria's DNA 'recipes'
21.08.2018 | University of Rochester
Protein interaction helps Yersinia cause disease
21.08.2018 | Schwedischer Forschungsrat - The Swedish Research Council
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
21.08.2018 | Ecology, The Environment and Conservation
21.08.2018 | Life Sciences
21.08.2018 | Power and Electrical Engineering