Corporate Banner
Satellite Banner
Molecular & Clinical Diagnostics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Enzyme-Activating Antibodies Revealed As Marker for Severe Rheumatoid Arthritis

Published: Thursday, May 30, 2013
Last Updated: Thursday, May 30, 2013
Bookmark and Share
Finding could lead to earlier diagnosis and new, more aggressive treatment for worst cases.

In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe cases of the disease, the immune system makes a unique subset of antibodies that have a disease-promoting role.

 Reporting in the journal Science Translational Medicine online May 22, the Johns Hopkins team describes how it found the novel antibodies to peptidylarginine deiminase 4, or PAD4, in blood samples from people with aggressive inflammation and connective tissue damage.

 Researchers say the presence of so-called PAD3/PAD4 cross-reactive autoantibodies could serve as the basis for the first antibody-specific diagnostic test to distinguish those with severe rheumatoid arthritis from those with less aggressive forms of the disease.

 “Identifying early on a subset of patients with severe rheumatoid arthritis could benefit their health, as these patients could start aggressive drug therapy immediately and find the most effective treatment option,” says senior study investigator Antony Rosen, M.D. Rosen, director of rheumatology and the Mary Betty Stevens Professor at the Johns Hopkins University School of Medicine, says that a third, or 1 million of the more than 3 million Americans – mostly women – estimated to have rheumatoid arthritis have an aggressive form of the disease.

 In the study, the antibodies were present – in 18 percent of 44 fluid samples from one research collection and in 12 percent of another collection of 194 – but only in people with severe cases of rheumatoid arthritis. Past research shows that those with the most aggressive disease are less likely to respond to anti-inflammatory treatments with steroids and other drugs.

 An examination of patients’ medical records revealed that 80 percent of patients with the antibody saw their disease worsen over the previous year, while only 53 percent without the antibody showed disease progression. In comparing average scores of disease-damaged joints, researchers found that those with the antibody had an average deterioration in joints and bones by a score of 49. Those without the antibody had an average degradation in their score of 7.5, indicating much milder disease.

 In a related finding, the Johns Hopkins team also uncovered how the PAD3/PAD4 cross-reactive auto-antibodies might contribute to more severe, erosive disease in rheumatoid arthritis. The team performed a series of experiments to gauge the antibodies’ effects on PAD4 in response to varying cell levels of calcium, on which PAD enzymes depend.

Lab experiments showed that the antibodies greatly increase PAD4 enzyme function at the low levels of calcium normally present in human cells. Results showed that PAD4 activity was 500 times greater in the presence of antibodies than when they were absent. Tests of the antibody and enzymes’ chemical structures later showed that the antibodies bind to PAD4 in the same region as calcium, suggesting to researchers that the antibodies might be substituting for calcium in activating the enzyme.

 According to Rosen, the series of experiments, which took two years to complete, represents the first evidence of an antibody having a direct role in generating the targets of the immune response, or auto-antigens, in rheumatoid arthritis.

 “Our results suggest that drugs inhibiting the PAD4 enzyme may have real benefit in patients with severe rheumatoid arthritis and represent an important field of study for investigating new and alternative treatments,” says lead study investigator and biologist Erika Darrah, Ph.D.

Darrah says the team next plans long-term monitoring of arthritis sufferers to find out when the antibody first appears in the blood, and when intervention may have maximum impact in preventing or stalling disease progression. The team also plans further experiments to see if the antibody is taking control of the chemical pathways normally used by other cell proteins to control PAD4 sensitivity to calcium.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

A Simple Blood Test May Catch Early Pancreatic Cancer
Currently, disease usually found too late to save lives.
Wednesday, October 30, 2013
Johns Hopkins Offers Latest Diagnostic Technology: 3-D Mammograms
New screening and diagnostic tool designed for early detection of breast cancer.
Tuesday, May 21, 2013
Diagnostic Errors More Common, Costly and Harmful Than Treatment Mistakes
In reviewing 25 years of U.S. malpractice claim payouts, researchers found that diagnostic errors accounted for the largest fraction of claims, the most severe patient harm, and the highest total of penalty payouts.
Wednesday, May 01, 2013
Scientific News
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Magnetic Nanoparticles May Reveal Early Traces Of Cancer
Rice University students’ computer program aids MD Anderson diagnostic initiative .
New Blood Test for The Earlier Diagnosis of Breast Cancer Spread
Researchers at University of Westminster have confirmed that a new blood test can detect if breast cancer has spread to other parts of the body.
Genetic Approach May Lead to New Treatments for Digestive Diseases
Researchers at UMass Medical School have identified a new molecular pathway critical for maintaining the smooth muscle tone that allows the passage of materials through the digestive system.
Biomarkers for Profiling Prostate Cancer Patients
Exiqon A/S has announced the publication of validation of prognostic microRNA biomarkers for the aggressiveness of prostate cancer in independent cohorts.
World-First Blood Test For Parkinson's
La Trobe University researchers have developed a world-first diagnostic blood test which could change the lives of people with Parkinson's disease.
Parsortix Demonstrates Benefits Over Marker-Based Systems
Research published online in the International Journal of Cancer, shows the ParsortixTM System efficiently captures and harvests intact, viable circulating tumour cells (CTCs), including EpCAM-negative CTCs, to allow for broader downstream CTC analysis.
Hepatitis C Virus Testing Guidelines Miss Too Many Cases
Urban emergency departments a good place to enact universal screening for adults.
NIH Sequences Genome of a Fungus
Researchers at the Institute have sequenced genome of human, mouse and rat Pneumocystis that cause life-threatening Pneumonia in immunosuppressed hosts.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!