Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breakthrough developments in rheumatoid arthritis reported

12.06.2007
Developments in rheumatoid arthritis reported at Federation of Clinical Immunology Services meeting in San Diego

Peter K. Gregersen, MD, stares at x-rays of hands, searching out the telltale signs of inflamed joints and wrists from his research subjects with rheumatoid arthritis. With these clinical features at his side, he turns to the basic building blocks of life – the human genome – to figure out what makes these people susceptible to the disabling inflammatory condition.

Dr. Gregersen has finally closed the circle between key genes identified in his laboratory at the Robert S. Boas Center for Genomics and Human Genetics at The Feinstein Institute for Medical Research in Manhasset, NY and more than a 1,000 patients with rheumatoid arthritis. The genes will help tell the story of how the immune system works to create specific antibodies that in turn increase a person’s risk for this crippling disease.

On Monday at the Federation of Clinical Immunology Services’ (FOCIS) meetings in San Diego, CA, Dr. Gregersen and his colleagues will be presenting the lab’s latest genetic findings. The group conducted genome-wide scans to identify polymorphisms, or genetic variants, that are associated with the inflammatory condition and can be used to understand the triggers of the disease. This will provide key insights into the pathways underlying rheumatoid arthritis and other autoimmune diseases. It may ultimately provide tests to predict who will respond to the available new treatments. Franak Batliwalla, PhD, also of The Feinstein Institute, will be presenting related studies on biomarkers and genetic influences on drug response at the same meeting.

Identifying Immune System Mediators

About one percent of the US population will develop rheumatoid arthritis, an autoimmune disease that leads to painful joint swelling. Scientists are cracking the genetic code that makes the immune system wage an attack on a person’s joints. Over the last decade, Dr. Gregersen and his colleagues have been amassing a genetic database complete with siblings with rheumatoid arthritis (and some family members without it) in an attempt to single out those genes that are involved in the autoimmune process. In fact, in 2004, they identified a gene called PTPN2 that confers a two-fold risk for rheumatoid arthritis and a number of other autoimmune diseases. The Feinstein now holds the largest collection from rheumatoid arthritis patients in the world.

Following the cellular pathway, it has been shown that PTPN22 influences the “trigger point” for activation of T-cells, immune cells that are normally called on to wage battle against infection. In autoimmune diseases like rheumatoid arthritis, PTPN22 appears to put people at higher risk of a wayward T-cell response.

The group has since gone on to use modern genetic methods to search for single nucleotide polymorphisms, or SNPs, to identify players that have fallen under the radar of older methods. The group has discovered another signaling molecule that seems to increase a person’s risk for rheumatoid arthritis by 30 percent. (The paper reporting the gene is in press.)

In collaborations with other scientists worldwide, Dr. Gregersen has also been able to show that certain markers are strongly linked to certain ethnic groups and others are not. “This will help us in figuring out what exactly is going on in this illness,” he said. “It’s pretty exciting.”

Early on in the rheumatoid arthritis research game, when HLA popped out as a major genetic player in the condition in the 1980s, Dr. Gregersen discovered that there was a shared bit of DNA that traveled in the disease. What took two years to identify in the laboratory – shared bands of genetic material – would take two days today. And that speed is what excites Dr. Gregersen. “We have the tools to get at these genes rather quickly now,” he said. “The more patients and controls that we have, the more power we will have to pull out new genes and make associations.”

In another major breakthrough, scientists have discovered the importance of a substance called citrulline as a target for immune attack in rheumatoid arthritis (RA). This immune system antibody associated with rheumatoid arthritis recognizes citrulline, which seems to be a key player in the condition. Indeed, the HLA associations with RA have now been shown by Dr. Gregersen and others to directly regulate the immune response to proteins containing citrulline. Citrulline is formed when a specific enzyme comes in contact with arginine, one of 20 common amino acids in proteins. When one of the enzymes is present, nitrogen is removed from the chemical structure of arginine and it converts into citrulline.

Laboratories have developed a test to measure for anti-cyclic citrullinated peptide antibody, or anti-CCP. It is now being used as a diagnostic for rheumatoid arthritis. Scientists are now finding that patients have CCP antibodies months or years prior to the illness, suggesting a way to identify the disease before it starts and perhaps offer treatments to stave off the symptoms. It turns out that those with these antibodies who also have a particular variety of HLA, a complex of genes that regulate immune function, have a 30 times higher risk of developing rheumatoid arthritis than those without these genetic risk factors.

Scientists at the University of Colorado are now analyzing the genes from 2,500 first degree relatives of rheumatoid arthritis patients and testing CCP levels to see whether there is a way to predict, based on these measurements, who will go on to develop rheumatoid arthritis.

Ultimately, understanding how the genes work to confer illness will help in the development of new treatments.

Normal Control Genetic Database

In addition, The Feinstein Institute is participating in a groundbreaking effort to release large amounts of genetic data on normal subjects for use by the scientific community. A key barrier to progress for many geneticists is the costs of obtaining genetic data from normal control populations to use for comparison to the genetic variation seen in people with disease.

In collaboration with the Children’s Hospital of Philadelphia, The Feinstein will release genetics data on approximately 6,000 normal volunteers. A company that designs new genetic testing technology, Illumina, Inc. will maintain the database and make it available to scientists. The data will not include personal identifiers but scientists will have information on age and ethnicity to best match their groups to study.

Terry Lynam | EurekAlert!
Further information:
http://www.nshs.edu
http://www.FeinsteinInstitute.org

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

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: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>