Navigation Links
A century-old puzzle comes together: Scientists ID potential protein trigger in lung disease sarcoidosis
Date:5/3/2010

Lung researchers at Johns Hopkins have identified a possible protein trigger responsible for sarcoidosis, a potentially fatal inflammatory disease marked by tiny clumps of inflammatory cells that each year leave deep, grainy scars on the lungs, lymph nodes, skin and almost all major organs in hundreds of thousands of Americans.

The disorder, whose cause has been a persistent mystery for nearly a century, strikes mostly young adults and disproportionately affects African Americans.

The link between sarcoidosis and overproduction of the suspected protein trigger, called serum amyloid A, was revealed after a six-year investigation encompassing more than two dozen laboratory experiments, including some on diseased lung tissue samples from 86 patients in the Baltimore area.

"The increase in production of serum amyloid A explains for the first time how inflammation can persist in the lungs without being triggered by an active infection," says study senior investigator and pulmonologist David Moller, M.D., a professor at the Johns Hopkins University School of Medicine. Moller is also director of the sarcoidosis clinic at The Johns Hopkins Hospital.

Study lead investigator Edward Chen, M.D., says the new findings also clear the path for developing drug treatments or vaccines that can block serum amyloid A from binding to cell receptors and kicking off inflammation.

In the short term, however, Moller says his team has plans to use the study results to create diagnostic tests that could better predict which people with the disease are likely to heal on their own or are more likely to suffer persistent inflammation, which can lead to scarring, difficulty breathing, and heart failure that can only be fixed by lung transplantation.

In a report published in February in the American Journal of Respiratory and Critical Care Medicine, the Johns Hopkins scientists described their research on what was behind the microscopic clusters of inflamed tissue and white blood cells, or granulomas, which are a defining feature of sarcoidosis.

Such lung lesions are not unique to sarcoidosis and can be triggered by infections, such as in tuberculosis, which is often confused with sarcoidosis. But unlike tuberculosis, sarcoidosis is not an infectious disease, does not yield to antibiotics, and is not limited to any particular organ, occurring as well in the eyes, skin, brain, heart and liver.

Of particular interest to researchers was the role played by so-called amyloids, a set of proteins known to cause other persistent inflammatory conditions, such as amyloidosis. Indeed, a different kind of amyloid has been tied to plaques in the brain tissue of people with Alzheimer's disease.

Key among the researchers' findings in sarcoidosis patients was that serum amyloid A stood out because it was heavily concentrated within the granulomas in diseased and scarred lung tissue. Researchers found the protein a hundred to a thousand times more widespread in sarcoidosis tissue samples than in samples from people with tuberculosis, another granuloma-forming lung disease. Similarly elevated amyloid levels were seen in comparison tests with tissue samples from people with lung cancer and Crohn's disease.

Further tests in patients' lung cell cultures showed that adding serum amyloid A spiked production of at least a half-dozen key inflammatory chemicals known to be involved in damaging tissue.

In another series of experiments in mice, the team discovered that granuloma formation in the lungs sped up when the mice were given injections of synthetic serum amyloid A. Mice had previously been injected with specially coated plastic beads designed to trigger sarcoidosis-like lesions. Adding the synthetic protein led to the same biochemical reactions in the mice as observed in humans, suggesting to the researchers that serum amyloid A played a key role in triggering sarcoidosis.

To better understand how serum amyloid A might be driving granuloma formation, the team used special antibodies to block various cell surface receptor sites where the protein would bind to the white blood cells and spur inflammation. Tests in human lung cells showed that blocking one particular receptor, toll-like receptor-2 (TLR2), inhibited the sustained inflammatory reaction typically associated with sarcoidosis. But when left to bind on its own, without an antibody blocking TLR2, the open receptor could attach to serum amyloid A, and raised production of inflammatory chemicals would ensue.

"Not only have we shown that serum amyloid A is a key protein trigger in sarcoidosis, but we also have evidence that the resulting inflammation is dependent on binding the protein at toll-like receptor-2, which opens up a host of possibilities that drugs blocking this binding site could prove an effective treatment for this disease," says Chen, an assistant professor at Johns Hopkins.


'/>"/>

Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. HIV researchers solve key puzzle after 20 years of trying
2. Three New Behavioral Health Companies Sign On With MyOutcomes
3. Transplant drug 2-year study outcomes show superior kidney function
4. Study shows liver transplant center impacts patient outcomes
5. Researchers make advances in understanding causes, treatments and outcomes of liver disease
6. New studies examine adverse outcomes associated with obesity and more applicable measures of obesity
7. Hair Loss Doctor Overcomes Odds To Produce First Ever Combination Topical Hair Growth Formula
8. Savvy Mom TV™ Welcomes Dr. Cynthia R. Green, Ph.D. as their Brain Health Expert
9. Typical Male Behavior Comes From Estrogen, Too
10. ATS systematic review: Critical care outcomes tied to insurance status
11. Complete revascularization improves outcomes for CAD patients
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... ... April 28, 2016 , ... Metabolic Nutrition ... at this week’s 2016 Europa Games Get Fit and Sports Expo in ... the Europa Orlando Expo coming up April 29-30, was selected as the perfect event ...
(Date:4/28/2016)... D.C. (PRWEB) , ... April 28, 2016 , ... The ... and Prevention (CDC) has established an ICD-10-CM code for sarcopenia, giving it recognition for ... the medical community effective October 1, 2016. , Sarcopenia is defined as a combination ...
(Date:4/28/2016)... (PRWEB) , ... April 28, ... ... an invitation to those affected by a health insurance co-operative bankruptcy to ... proprietary process, individuals can receive over 1,500 FDA-approved prescription medications from over ...
(Date:4/28/2016)... ... April 28, 2016 , ... Today ... the Protocol Calendar Exchange , is officially open to all sponsors in ... available for sites to download into their clinical trial management system (CTMS), which ...
(Date:4/28/2016)... , ... April 28, 2016 , ... ... Chief Medical Officer at the Steadman Philippon Research Institute in Vail, Colorado, ... to raise awareness about the debilitating and costly musculoskeletal disorders that are ...
Breaking Medicine News(10 mins):
(Date:4/28/2016)... April 28, 2016   Click here for ... Inc. (NYSE: DPLO), the nation,s largest independent specialty ... definitive agreement to acquire Valley Campus Pharmacy, Inc., ... a leading specialty pharmacy that provides individualized patient ... . In 2015, TNH generated approximately $400 ...
(Date:4/28/2016)... NEW YORK , April 28, 2016 /PRNewswire/ ... will notably complement the company,s valve repair and ... the move also places Abbott more firmly into ... one of the fastest growing device areas, with ... to its recent report,  Advanced Remote Patient ...
(Date:4/28/2016)... Research and Markets has announced the addition ... report to their offering.      (Logo: ... plastic surgery products market is expected to grow at ... ,The growing adoption of laser in aesthetics is another ... Lasers are used to treat a broad range of ...
Breaking Medicine Technology: