The researchers worked with transgenic mouse models that were engineered to overproduce a special cytokine – a hormone which regulates immunity – called BAFF, a B-cell activating factor that is elevated in patients with lupus and other autoimmune diseases. The B cells are responsible for the production of antibodies in the body. Mice overproducing BAFF develop systemic lupus erythematosis (SLE)-like disease, very similar to human lupus, which is estimated to affect one in a thousand Americans, 90 percent of them women.
The research study showed that that a compartment of the spleen called the marginal zone is where the majority of autoreactive B cells are found. The scientists transplanted immune cells from the spleen's marginal zone in the mice with lupus into mice without their own B cells, and found that they immediately gave rise to pathogenic antibodies.
When the enlarged marginal zone cell pool in the mouse model was removed or reduced, the disease was prevented or strongly diminished.
"The study proved without a doubt that the transplanted B cells were the source of lupus auto-antibodies," said Gregg Silverman, M.D. professor of medicine in UCSD’s Translational Oncology Program and contributor to the paper. "Identifying the spleen’s marginal zone as the likely source of these tissue-damaging antibodies gives us important insights into the cause of lupus as well as a target for new therapies."
The researchers also studied B-cell activation in two signalling pathways, called the classical and alternative NF-ÿB pathways, that contribute to the development of lupus. The scientists discovered that while each pathway is required for the pathogenesis of antibodies that cause the autoimmune disease, neither works alone.
"Either pathway would be a suitable target for therapy,” said Karin, whose lab first identified the two NF-ÿB pathways several years ago. "Both are critical to production of pathogenic B cells that destroy the body's own cells in lupus." However, he added that targeting one of the NF-ÿB pathways called the classical pathway would eliminate B cells throughout the entire body. This is the drawback of other therapies currently recommended for lupus patients, as they destroy the body’s immune cells which are needed to fight off other infection.
Karin added that genetic manipulation of the animals, or the timing of the splenectomy in the cycle of the lupus-like disease might have contributed to the outcome. Therefore more research is needed to draw a definite conclusion, though their studies ruled out the lymph nodes or the bone marrow – where B cells are born – as contributors to the effect.
"The study tells us important things about the pathogenesis of disease in a mouse model that is very close to human lupus," Karin said. In mice, as in humans, the disease leads to overproduction of anti-DNA antibodies and immune deposits in the kidneys, which can result in fatal kidney damage.
Lupus is a chronic autoimmune disease that, for unknown reasons, causes the immune system to attack the body's own tissue and organs, including the joints, kidneys, heart, lungs, brain, blood, or skin. Difficult to diagnose and treat, patients may see several physicians before learning they have lupus. The disease is much more common in women than men, usually is first diagnosed between the ages of 15 and 44 years, and is two to three times more common in persons of color. Patients often take many different medications to control lupus, which has symptoms ranging from mild to life-threatening, including aching or swollen joints, skin rashes, kidney damage, anemia and hair loss.
Debra Kain | EurekAlert!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy