UCLA researchers have uncovered new clues that may explain why Graves’ disease (GD) attacks the muscle tissue behind the eyes, often causing them to bulge painfully from their sockets, as in the late actor Marty Feldman.
Scientists at UCLA’s Jules Stein Eye Institute and Harbor-UCLA Medical Center discovered defects in the infection-fighting T-cells of GD patients’ immune systems. Reported March 1 in the Journal of Immunology, their study may deepen understanding of how the autoimmune disorder damages the body and offer a new target for treating the disfiguring disease.
Earlier research found that GD patients’ immune systems produce an antibody that other people do not. Not recognizing the patient’s thyroid as "self," the antibody mistakenly mounts an attack against the organ, causing inflammation and damage to the body, including eye tissue.
In the current study, UCLA researchers discovered that T-cells taken from GD patients contain an abnormal surplus of the receptor targeted by this antibody. An antibody must latch to a specific receptor – like a key into a lock -- in order to elicit a cellular response. The receptors mobbed the patients’ immune systems, even on T-cells that normally would not produce them.
"We didn’t know why GD patients’ cells created a new antibody, but had a hunch that that it sprang from an immune abnormality," explained Dr. Raymond Douglas, first author and assistant professor of ophthalmology at the Jules Stein Eye Institute. "Because T-cells are the generals of the immune system and lead the attack in any immune response, we assumed that they played a key role in this antibody’s development."
The team tested GD patients’ blood for the antibody and compared their findings to samples from healthy people, with about 100 subjects in each group. The new antibody was found in almost all of the GD patients’ blood.
The new antibody binds to the excess receptors on the T-cells, mimicking the actions of a hormone called IGF-1, or insulin-like growth factor 1. Similar to insulin, IGF-1 stimulates cell growth while suppressing normal cell death. The team suspects that this mechanism prolongs the survival of older T-cells, causing a cascade of autoimmune problems that spur the body to attack its own tissue.
"We think that the extra receptors allow the new antibody and IGF-1 to disrupt the programming of the T-cells," said principal investigator Dr. Terry Smith, professor of medicine at the David Geffen School of Medicine and chief of molecular medicine at Harbor-UCLA Medical Center.
"The antibody provokes the receptor to signal the T-cell to grow and multiply – long after the cell was programmed to die," he explained. "After two or three generations of this process, we suspect that the high-jacked T-cells mutiny over the normal T-cells, sparking the body’s immune reaction against itself."
The next step is to identify what the T-cells are reacting to and how the receptor enables the cells to survive beyond their normal lifespan. The team plans to develop an antibody drug to block the receptor from interacting with the T-cells and slow down the disease.
In Graves’ disease, the thyroid gland goes into overdrive, producing excess levels of hormone that attack the tissue behind the eye, causing them to protrude. In extreme cases, patients experience trouble closing their eyelids, severe double vision, corneal scarring, optic nerve damage and even blindness.
Graves’ disease is nine times more common in women than men. The disorder most often strikes during the childbearing years, and runs an average course of one to two years. No cure exists, though surgery can be done at the end stage to correct disfigurement.
Enrique Rivero | EurekAlert!
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News