Corporate Banner
Satellite Banner
Genotyping & Gene Expression
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
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 2,400+ scientific posters on ePosters
  • More than 3,700+ 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

New Autism-Causing Genetic Variant Identified
Novel approach expected to be useful for other diseases too.
Saturday, March 28, 2015
A Simple Blood Test May Catch Early Pancreatic Cancer
Currently, disease usually found too late to save lives.
Wednesday, October 30, 2013
Molecular Marker Predicts Patients Most Likely to Benefit Longest From Two Popular Cancer Drugs
Preliminary study needs further confirmation.
Wednesday, September 11, 2013
Cancer-Linked Fam190a Gene Found to Regulate Cell Division
A little-described gene known as FAM190A plays a subtle but critical role in regulating the normal cell division process known as mitosis.
Monday, July 08, 2013
Scientific News
How a Kernel Got Naked and Corn Became King
Ten thousand years ago, a golden grain got naked, brought people together and grew to become one of the top agricultural commodities on the planet.
New Tool For Investigating RNA Gone Awry
A new technology – called “Sticky-flares” – developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
Oxitec ‘Self-Limiting Gene’ Offers Hope for Controlling Invasive Moth
A new pesticide-free and environmentally-friendly way to control insect pests has moved ahead with the publication of results showing that Oxitec diamondback moths (DBM) with a ‘self-limiting gene’ can dramatically reduce populations of DBM.
Teeth Reveal Lifetime Exposures to Metals, Toxins
Researchers have identified dental biomarkers to reveal links between early iron exposure and late life brain diseases.
Scientists Identify Schizophrenia’s “Rosetta Stone” Gene
Scientists have identified a critical function of what they believe to be schizophrenia’s “Rosetta Stone” gene that could hold the key to decoding the function of all genes involved in the disease.
Could a simple saliva test detect Alzheimer's?
Researchers have presented findings suggesting that a simple, non-invasive diagnostic for Alzheimer's could be within reach.
New Research Advances Genetic Studies in Wildlife Conservation
‘Next-gen’ DNA sequencing of non-invasively collected hair expands field of conservation genetics.
AncestryDNA and Calico to Research the Genetics of Human Lifespan
Collaboration will analyze family history and genetics to facilitate development of cutting-edge therapeutics.
Gene Variation Identified for Teen Binge-Eating
Researchers have identified a gene variant which can lead to teenage binge eating, they hope that their work will inform the development of future preventative measures.
Skyscraper Banner

Skyscraper Banner
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
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!