Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A single sugar found responsible for an antibody's ability to treat inflammation

07.08.2006
For years, researchers have struggled to understand how IVIG worked. It's ability to treat autoimmune diseases seemed to bean apparent contradiction.

Intravenous immunoglobulin (IVIG) is a complex mixture of IgG antibodies made from human plasma that contains the pooled antibodies from thousands of people, and is only FDA-approved to treat a few assorted conditions; nonetheless, practitioners have used it off-label with varied success in patients with lupus, arthritis and asthma, among other autoimmune disorders. In the body, the antibodies in plasma act as part of the immune response to identify and deactivate foreign invaders. When they begin attacking the body's own cells, the same protective immunoglobulins (known as IgG antibodies) can cause autoimmune disorders like lupus, arthritis and asthma. And yet, when IVIG is infused into people with those exact autoimmune conditions, it calms inflammation rather than causes it.

Jeffery Ravetch, Theresa and Eugene M. Lang Professor and head of Rockefeller's Laboratory of Molecular Genetics and Immunology, was struck by this inconsistency. "If IgG triggers autoimmune disease, how could it be pathogenic and therapeutic?" he asked. "We call it the IgG paradox." Six years ago he started an investigation into exactly how IVIG worked, and what he's discovered could one day lead to a whole new class of therapeutics. In a paper published today in the journal Science, Ravetch and his colleagues, Falk Nimmerjahn and Yoshi Kaneko explain what makes IVIG effective: A small fraction of the IgG antibodies in the IVIG solution carry a sugar called sialic acid that is required for its protective ability.

IgG antibodies bind to and activate specific immune cells, with different forms or "subclasses" binding to specific receptors (called Fc receptors) on the immune cell's surface. Antibody subclasses have different abilities to induce inflammation in the body by virtue of their selective ability to engage either activating or inhibitory Fc receptors. Earlier work had shown that IVIG infusion changed this ratio of activating and inhibitory receptors on the cells that trigger inflammation, rendering the pro-inflammatory autoantibodies in autoimmune diseases, like lupus and arthritis, less inflammatory. The next logical step then, Ravetch says, was determining how the IgG molecules in IVIG preparation could have an anti-inflammatory effect.

Because a therapeutic, anti-inflammatory response to IVIG requires a concentration of IgG antibodies that's hundreds of times greater than is normally used for antibody therapy for cancer or infection, for example, Ravetch and his colleagues began to look for something that was only present in IVIG in small amounts. That's how they discovered that just the very terminal sialic acid on the Fc portions of the IgG molecule were the root of the anti-inflammatory activity. When the researchers removed the sialic acid, the molecule retained its structure and its half-life, but it lost its protective abilities. "This is a very interesting condition that's set up," Ravetch says. "IgG can shift from a state that is quite inflammatory to a state that is actively anti-inflammatory by just changing a sugar." This switch occurs during a normal immune response to a foreign substance, shifting the IgG antibodies from an anti-inflammatory state to one that is pro-inflammatory and able to efficiently dispose of the foreign challenge.

To test the theory, Ravetch and his colleagues tried enriching IVIG for the IgG molecules that contained sialic acid. They found that just enriching for this IgG species increased IVIG activity by a factor of ten, while removing it wiped out the therapeutic activity altogether. This discovery, Ravetch says, has potentially huge implications, and his lab is now working to generate a recombinant form of IgG that, by virtue of a sialic acid molecule attached in the right place, will be anti-inflammatory and could act as a novel treatment for autoimmune disorders. "We have the opportunity to make a much better form of IVIG that will work 100 times better and be a pure molecule--to build a much better class of therapeutics based on a property that already exists in nature."

Kristine Kelly | EurekAlert!
Further information:
http://www.rockefeller.edu

More articles from Health and Medicine:

nachricht Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Foods of the future
15.08.2018 | Georg-August-Universität Göttingen

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

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...

Im Focus: Color effects from transparent 3D-printed nanostructures

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...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

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...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

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....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

20.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>