DNA sequences obtained from a handful of patients with multiple sclerosis at the University of California, San Francisco (UCSF) Medical Center have revealed the existence of an "immune exchange" that allows the disease-causing cells to move in and out of the brain.
The cells in question, obtained from spinal fluid and blood samples, are called B cells, which normally help to clear foreign infections from the body but sometimes react strongly with the body itself. One of the current theories of multiple sclerosis, which strikes hundreds of thousands of Americans and millions more worldwide, holds that the disease manifests when self-reactive B cells in the brain become activated and cause inflammation there.
The apparent exchange of the cells between the brain and the blood may be a key to unlocking better treatments and diagnostics, because the activated B cells causing problems in the brain may be accessible when they move from the brain to the periphery.
"The hope is that if we can identify culprit B cells, using precise tools, we will be able to better diagnose multiple sclerosis and monitor disease activity. In addition, in ways that may have to be tailored for each patient, this may also allow us to develop therapies that directly target disease-causing B cells," said UCSF neurologist Hans Christian von Büdingen, MD, who led the research.
Described this week in the Journal of Clinical Investigation, the work is the latest from the UCSF Multiple Sclerosis Center, part of the UCSF Department of Neurology and one of the leading programs in multiple sclerosis research and patient care worldwide.
Since 2008, a UCSF team led by the chair of the Department of Neurology, Stephen Hauser, MD, has completed two clinical trials that showed, in essence, that blocking B cells may stop the attacks, or flare-ups, that occur in people with multiple sclerosis. These trials used Rituximab and Ocrelizumab, both of which target a molecule called CD20 found on the surface of B cells.
The new work suggests that targeting B cells could be extended into a precision strategy that would specifically tailor treatments to the exact identity of the B cells at work in any one patient.
Background on B cells and Multiple Sclerosis
Multiple sclerosis is a common, chronic disease affecting some 350,000 Americans whose immune systems periodically attack the myelin sheaths that insulates nerve fibers in the brains and spinal cord. Damage to the sheaths can short-circuit signals traveling along the nerve fibers, disrupting the normal flow of communication from the brain and causing a range of symptoms.
The disease is about three times more prevalent among women than men, and for reasons scientists do not understand, the number of women who have the disease has been increasing in proportion to men. Decades ago, there were about as many men as women with multiple sclerosis.
That disparity is not the only mystery surrounding multiple sclerosis. The severity of the disease can vary wildly, from people who have mild disease, rarely having symptoms, to people who suffer significant deficits for long periods of time, sometimes progressively, with weakness, sensory disturbance, fatigue, visual impairments and loss of coordination. In addition, scientists do not understand what triggers MS attacks, though researchers at UCSF and elsewhere are actively investigating a number of possible genetic and environmental triggers, including low vitamin D levels.
There also is a need to find better ways to diagnose, monitor and track the disease – a need that may be helped by the new discovery.
"We don't have any specific diagnostic tool at this point – no biomarker that we can look for to say, 'this is multiple sclerosis'," von Büdingen said.
The article, "B cell exchange across the blood-brain barrier in multiple sclerosis" by H.-Christian von Büdingen, Tracy C. Kuo, Marina Sirota, Christopher J. van Belle, Leonard Apeltsin, Jacob Glanville, Bruce A. Cree, Pierre-Antoine Gourraud, Amy Schwartzburg, Gabriella Huerta, Dilduz Telman, Purnima D. Sundar, Tyler Casey, David R. Cox and Stephen L. Hauser was published online by the Journal of Clinical Investigation on Nov.19, 2012. See: http://dx.doi.org/10.1172/JCI63842
In addition to UCSF, authors on this study were affiliated with Applied Quantitative Genotherapeutics and Protein Engineering, which are both divisions of Rinat-Pfizer Inc.
This work was supported by grants from Pfizer Inc., The Nancy Davis Foundation, and the National Institutes of Health through grant #R01NS026799, #R01NS049477, and #K02NS072288.
Additional supported was provided by an endowment from the Rachleff Family Foundation, a FCMSC Research Scholarship and a PACCTR Short-Term Fellowship from UCSF.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.
Jason Socrates Bardi | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction