A cell type that causes significant scarring in lung disease appears to have a similar effect in Graves' disease, University of Michigan Health System researchers have found. The cells, called fibrocytes, are present at a higher than normal frequency in patients with Graves' disease, according to a new study, the first to associate fibrocytes with this autoimmune disease.
The discovery is a major step forward in explaining how and why the orbit of the eye is subject to scarring and inflammation in Graves' disease.
The findings may also lead to new treatment strategies to target scarring or fibrosis, say authors Raymond Douglas, M.D., Ph.D., and Terry Smith, M.D., specialists in Graves' disease at the University of Michigan Kellogg Eye Center. The study appears in the January issue of the Journal of Clinical Endocrinology & Metabolism.
Graves' disease is an autoimmune disorder which results in an overactive thyroid. Up to half of those affected by the disease will develop inflammation or fibrosis around their eyes, creating the bulging appearance associated with Graves' eye disease, also called thyroid-associated ophthalmopathy. Excessive scarring can cause such manifestations as double vision or even loss of vision.
"Today we have medications to reduce inflammation, but these drugs typically do not treat the fibrotic effects of thyroid eye disease," says Douglas, oculoplastics surgeon. "Our study is the first to implicate fibrocytes in the disease process, a finding that should open up new possibilities for treatment."
Fibrocytes are immune cells derived from bone marrow that circulate through the bloodstream. They can infiltrate tissue, like the lungs, kidney, and liver, generating excess connective tissue and areas of fibrosis, for example, following pulmonary or kidney injury.
To determine whether fibrocytes play a similar role in Graves' disease, these investigators and their colleagues examined tissue samples from 70 patients with the disease and compared them to 25 healthy subjects. The samples were gathered while Douglas and Smith were on the faculty of the University of California at Los Angeles.
They found that fibrocytes were present at substantially higher frequencies—as much as five times greater—in patients with Graves' disease. These levels were observed in both the bloodstream and in the orbital tissues of patients who had developed thyroid eye disease.
In earlier studies, Douglas and Smith identified the antigens that trigger the overactive immune response in Graves' disease. Now they report that fibrocytes express the same antigens: thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor-1 receptor (IGF-1R). In addition, the Kellogg researchers say, when these receptors are activated, they produce a large quantity of cytokines which could stimulate immune cells to the orbit, causing inflammation in thyroid eye disease.
"We now have a much clearer picture of the disease process, including the pathway by which fibrocytes reach the orbit," says Douglas. "Drugs currently under development for other fibrotic diseases are designed to disrupt this pathway and prevent fibrocytes from reaching their target." According to Douglas, "These therapies may be just as effective for our patients with thyroid eye disease."
As follow-up to the study, the Kellogg researchers plan to more fully identify the role of fibrocytes in the disease process and test whether several new agents, such as rituximab, can reduce these cells as they circulate through the bloodstream. The authors also recently demonstrated that rituximab was highly effective in treating patients with severe Graves' disease.
Reference: Increased Generation of Fibrocytes in Thyroid-Associated Ophthalmopathy, Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2009-1614
Funding support includes grants from the National Institutes of Health, Research to Prevent Blindness, and the Bell Charitable Foundation.
Kellogg Eye Center: Graves' Eye Disease http://www.kellogg.umich.edu/patientcare/conditions/graves.disease.html
Related news: Researchers find new way to attack inflammation in Graves' eye disease (11/6/2009) http://www2.med.umich.edu/prmc/media/newsroom/details.cfm?ID=1367
Betsy Nisbet | EurekAlert!
Antarctic Ice Sheet mass loss has increased
14.06.2018 | Technische Universität Dresden
WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences