Infection with lymphocytic choriomeningitis virus triggers expression of a factor called TOX in immune cells strengthening their migration into the brain and promoting damaging effects, including inflammation and tissue destruction. These findings represent a new piece of the puzzle about the mechanism underlying autoimmune diseases like multiple sclerosis (MS).
T-cells
Exposure to fracking chemicals during pregnancy may aggravate multiple sclerosis (MS) severity and induce an earlier start of symptoms, a new study in mice suggests. The study, “Developmental Exposure to a Mixture of 23 Chemicals Associated With Unconventional Oil and Gas Operations Alters the Immune System…
Genentech’s Ocrevus (ocrelizumab) reduces levels of cerebrospinal fluid biomarkers that denote nerve cell damage in multiple sclerosis patients, a Phase 3 clinical trial shows. Researchers will present the results at the American Academy of Neurology’s annual meeting in Los Angeles, April 21-27. The presentation will be titled “Interim Analysis of the…
High levels of a protein called calnexin in the brain may disrupt the blood-brain barrier of patients with multiple sclerosis, a Canadian study suggests. The finding could lead to new treatment strategies to prevent brain damage in MS. The research, “Calnexin is necessary for T cell…
A combination therapy of low-dose methylprednisolone and interferon (IFN)-beta-secreting stem cells is effective in a mouse model of multiple sclerosis (MS), a new Korean study suggests. The research, “Effective combination of methylprednisolone and interferon β-secreting mesenchymal stem cells in a model of multiple sclerosis,” appeared in the…
A cell recycling process helps trigger an immune response against myelin, the protective layer covering nerve cell axons to aid in signal transmission, a multiple sclerosis (MS) study indicates. When University of Zurich researchers eliminated the process, mice developed much milder forms of an MS-like disease. Loss of myelin is the…
Exposure to certain gut bacteria at a young age may cause multiple sclerosis (MS) and fuel its progression, a new mouse study shows. The study, “Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood,” appeared in the journal Proceedings of the National…
MS News That Caught My Eye Last Week: Older Patients, Stem Cells, Myelin, B-cells vs. T-cells
#MSParis2017 – Trial to See if Disease-modifying Therapies Not Necessary in Older MS Patients This tops my list this week because, at age 69, I certainly fit the definition of an “older” MS patient. The study is hoping to enroll 300 MS patients in the U.S. who…
News commentary One particular session on Day 2 of the four-day 7th Joint ECTRIMS-ACTRIMS Meeting — which drew 10,000 researchers, doctors, industry representatives, and patient advocates to hear about advances in multiple sclerosis (MS) treatment and understanding — attracted so much interest that all seats were taken in the…
Propionic acid supplements alter the composition and behavior of immune cells in multiple sclerosis (MS) patients — likely by changing the composition of gut bacteria, according to Alexander Duscha from Ruhr University Bochum in Bochum, Germany. The finding, presented Wednesday at the 7th Joint ECTRIMS-ACTRIMS Meeting running in Paris…
Atara Biotherapeutics has started a Phase 1 clinical trial to assess ATA188’s safety and potential to treat progressive or relapsing-remitting multiple sclerosis. ATA188 is the company’s next-generation T-cell immunotherapy. It targets Epstein-Barr virus antigens that play an important role in the development of MS. An antigen is a molecule capable of…
Inhibiting an enzyme prevented mice from developing a multiple sclerosis-like disease, a European study reports. The finding about HDAC1, a member of the histone deacetylases family of enzymes, could open up new therapy possibilities for MS. Researchers published their study, “A T cell-specific deletion of HDAC1 protects against experimental…
(Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this column about terms starting with the letter H.) Symptoms of MS Hemiparesis (and hemiplegia) When someone with MS experiences weakness along one entire side of the body, they…
Chronic stress and inflammation in the brain can cause multi-organ dysfunction including severe gut failure, mediated by a newly identified nerve pathway in animal models of multiple sclerosis, a Japanese study shows. MS is an autoimmune disease caused by CD4+ T-cells that cross the blood-brain barrier protecting the central nervous system. This inflames and stresses the brain and spinal cord. In previous studies, a team led by professor Masaaki Murakami of Japan's Hokkaido University showed that these cells could cross the blood-brain barrier in specific sites. These entrance sites depend on brain regional activation, which was found to be triggered by specific nerve interactions — a mechanism the team called gateway reflexes. In collaboration with other Japanese researchers and a team from Germany, the project aimed to address the potential correlation among chronic stress, brain inflammation and organ failures in MS. Using mice with MS-like disease — the experimental autoimmune encephalomyelitis model — researchers found that animals that had autoreactive CD4+ T-cells and which were exposed to stressful conditions developed severe symptoms such as gastrointestinal failure, or even death. Detailed analysis of the animals' brains showed that in stressed mice, CD4+ T-cells accumulated in two specific sites in the center of the brain around blood vessels. This event would cause inflammation around those vessels, and activation of a nerve pathway that is commonly turned off. This switch led to gut dysfunction, bleeding and failure. "These results demonstrate a direct link between brain micro-inflammation and fatal gastrointestinal diseases via the establishment of a new neural pathway under stress," Murakami, the study's senior author, said in a news release. Researchers were able to prevent gut symptoms by inhibiting inflammation in the brain or blocking the nerve pathway responsible for driving the signals from the brain to the gastrointestinal tract. "Micro-inflammation in the brain is also seen in Alzheimer's disease and Parkinson's disease," Murakamai concluded. "So it's of particular interest to investigate possible connections between brain micro-inflammations and organ dysfunctions, including those within the brain itself, in those patients."
A new study highlights a crucial role for the enzyme protein tyrosine phosphatase N2 in the development of early immune T-cells, and suggests that decreased levels of this enzyme can lead to the production of subsets of T-cells that contribute to the development of autoimmune diseases such as multiple sclerosis. T-cells, which are a type of immune cells that fight infection, are composed of multiple subsets that have different roles in immunity. Researchers at Monash University set out to characterize the role of PTPN2 in early T-cell development and in the development of T-cell subsets αβ TCR and γδ TCR. To do this, researchers deleted the gene coding for PTPN2 and looked at the resulting T-cell population. Results demonstrated that the deletion of PTPN2 led to the production of γδ T-cells with pro-inflammatory properties that have been associated with many autoimmune diseases by inhibiting certain pathways that regulate proper T-cell development. “This is an important advance in our understanding of critical checkpoints in T-cell development,” Tony Tiganis, principal research fellow in the Department of Biochemistry and Molecular Biology at Monash University in Australia, said in a press release. “It helps decide whether the progenitors go on to become T-cells or something else; if they become one type of T-cell or another type.” Interestingly, there are already drugs that target some of the pathways that PTPN2 regulates, which could lead to the use of existing drugs to treat some of these autoimmune diseases, including MS. “Understanding the mechanisms that govern early T-cell development and how these are altered in human disease may ultimately afford opportunities for novel treatments. This is very exciting,” said Florian Wiede, a post-doctoral candidate at Monash and first author of the study.
New analyses of how Merck’s Mavenclad (cladribine tablets) act to treat relapsing multiple sclerosis (MS) give researchers an entirely new picture of immune processes leading to the disease. Data showed that the drug lowers both immune B-cells and, to a lesser degree, T-cells. But the numbers of both cell…
Stressful Environment Triggers Inflammatory Cells Linked to Autoimmune Diseases Like MS, Study Shows
A stressful microenvironment, characterized by low metabolites and low oxygen levels, triggers the generation of immune cells directly implicated in a variety of inflammatory diseases, such as multiple sclerosis (MS). The study, “Cellular Stress in the Context of an Inflammatory Environment Supports TGF-β-Independent T Helper-17 Differentiation,” was…
Unpublished Data May Point to Link Between Lemtrada and Other Autoimmune Diseases in MS Patients
Previously unpublished results of clinical trials of Lemtrada (alemtuzumab) appears to contain key information as to why many multiple sclerosis patients who use it develop other autoimmune diseases. Researchers looked at the immune cell mix after Lemtrada depleted many of those cells. They discovered that certain B-cells repopulate the body earlier…
Already an approved treatment for relapsing and primary progressive multiple sclerosis (MS), Ocrevus (ocrelizumab) is still undergoing scrutiny in several clinical trials. Most focus on the drug’s effects in specific patient groups, but one study aims to advance understanding of how Ocrevus works to harness disease. To do so, the open-label Phase 3…
MS brain inflammation is a result of interactions between processes in the brain and the rest of the body, with interferon-gamma (IFN-gamma) being a key player, according to a detailed analysis of cytokines in the spinal fluid and serum of MS patients. Russia’s Kazan Federal University found that IFN-gamma activates other…
A cytomegalovirus infection triggers an increase in inflammatory and cytotoxic immune cells in mice with multiple sclerosis (MS), which leads to enhanced inflammation and loss of nerve-protecting myelin. The study, “Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation,” was published in the journal Scientific Reports. A cytomegalovirus (CMV) infection…
The use of antibiotics in childhood, which alters the microbiome — or natural bacteria flora in the gut — may increase the risk of multiple sclerosis (MS), inflammatory bowel disease (IBD) and other inflammatory diseases, according to an Australian study. The mouse study, “Early-life antibiotic treatment enhances the…
Dr. Stephen Hauser, chair of the neurology department at the University of California San Francisco, was instrumental in the early research and later clinical trials that ultimately led to Ocrevus (ocrelizumab), the first therapy approved by the U.S. Food and Drug Administration (FDA) for both relapsing MS (RMS) and primary progressive multiple sclerosis…
Scientists at the University of Maryland have developed an experimental treatment to control the immune system and recover movement in a paralyzed mouse model of multiple sclerosis (MS). The team presented its research April 2 during the 253rd National Meeting & Exposition of the American Chemical Society in San Francisco. In…
Scientists have identified a receptor that promotes the influx of damaging immune T-cells into the brain of a mouse model of human multiple sclerosis (MS). The study, “EBI2 is highly expressed in multiple sclerosis lesions and promotes early CNS migration of encephalitogenic CD4 T cells,” appeared in the…
It is no coincidence that multiple sclerosis (MS) patients are prone to airway infections, according to research showing that MS disease processes allow suppressive immune cells to travel to the lungs and block inflammatory responses against invading viruses. The study may offer guidance on how vaccines should be used to…
Short-chain dietary fatty acids, such as propionate, drive the production of regulatory immune T-cells in patients with multiple sclerosis (MS), while long-chain acids promote T-cells that are involved in inflammatory processes. Since the beneficial fatty acids are safe and can be obtained as over-the-counter dietary supplements, researchers suggest they could…
#ACTRIMS2017 – Airway Infections May Be More Common in MS Due to Altered Immune Response in Lungs
Disease processes in multiple sclerosis (MS) likely contribute to the increased sensitivity to airway infections seen in MS patients, a series of experiments in mice demonstrated. The study, presented at the ACTRIMS 2017 Forum, showed that suppressive immune cells travel to the lungs and prevent an essential inflammatory reaction to viral…
Researchers have identified two factors that allow Th17 cells — which drive multiple sclerosis (MS) and other autoimmune conditions — to form memory cells in the body and cause repeated symptom flare-ups. Knowing the identity of the molecules, which are immune mediators called cytokines, will make it possible for scientists to search…
In a new and possibly important insight into the workings of the immune system, researchers discovered what it takes for T-cells to start targeting myelin sheets in multiple sclerosis (MS). The findings may also explain why some drugs fail to prevent autoimmunity in MS. The study, “Trans-presentation…