immune system

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…

(Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this column about terms starting with the letter I.) Symptoms of MS Incontinence A common symptom of MS, incontinence refers to an inability to control one’s…

Striking similarities between patients with multiple sclerosis and a type of schizophrenia suggest the disorders are related, according to a review of a number of studies. Dr. Boris M. Arneth wrote the article, “Multiple Sclerosis and Schizophrenia.” It was published in the International Journal of Molecular Sciences. MS…

Merck’s Mavenclad tablets significantly improve quality of life among relapsing multiple sclerosis patients while reducing the number of relapses, according to new analyses of previously unpublished data from clinical trials assessing the drug. This new data, published in the Multiple Sclerosis Journal, come just as the European Commission ponders whether to approve the once- rejected therapy to treat relapsing forms of MS. Its decision is expected later this month, seven years after a perceived increased of cancer risk led the European Medicines Agency (EMA) to block Mavenclad. In 2011, the U.S. Food and Drug Administration (FDA) rejected the medication, forcing its eventual withdrawal from the Australian and Russian markets, where it had already been licensed. For the study, researchers at Queen Mary University of London used data obtained from the EMA through a Freedom of Information request. They analyzed data from the Phase 3 CLARITY trial, which compared Mavenclad to placebo. The trial's 1,326 participants completed a quality-of-life questionnaire that focused on disease aspects such as mobility, self-care, usual activities, pain or discomfort, and anxiety. After two years, those on Mavenclad had significantly improved their quality of life compared to the control group, particularly in terms of self-care. Mavenclad also helped mobility, which might be related to its ability to prevent relapses and delay progression, researchers said. While researchers assessed quality of life using two different questionnaires, patients had only completed one in sufficient numbers to allow for a solid analysis. The other quality-of-life tool provided researchers with numerically positive results, but the low number of responses made the result difficult to interpret. This wasn't the first time QMUL researchers have contributed in this way to knowledge of Mavenclad in MS. In 2015, they used a Freedom of Information request to obtain data showing that Mavenclad was not related to increased cancer risk. “Cladribine seemed to have such excellent potential as a treatment for MS that we thought it was tragic the development program was shelved, and significant parts of the clinical trial data remained unpublished,” study leader Klaus Schmierer, a neurologist at both QMUL and Barts Health NHS Trust, said in a press release. “In addition to the drug being highly effective, well tolerated and safe as far as short-term studies can show, we now know it also improves patients’ quality of life. The new results seemed so clear, we felt it was extremely important to publish and share these data." Mavenclad has now been studied in some 2,700 patients with relapsing MS in the Phase 3 trials CLARITY, CLARITY EXTENSION, and ORACLE-MS, as well as the Phase 2 ONWARD trial, and the ongoing long-term study PREMIERE. The treatment differs from most other oral MS therapies in that a short treatment course — a maximum 20 days — triggered effects that were upheld for two years. Studies of Mavenclad’s mechanisms suggest the drug gets such results by resetting the immune system. In June 2017, the EMA's Committee for Medicinal Products for Human Use urged the European Commission to approve Mavenclad. Merck also plans to seek U.S. approval for its therapy and is now in talks with the FDA about Mavenclad's future.

A new and potentially important mechanism in the development of autoimmune diseases like multiple sclerosis was discovered by scientists at the University of Freiburg, Germany. They identify a protein, called Caveolin-1, that is essential to immune cells called B-cells working as intended to protect a person from pathogens or — in its absence…

A bacteria present in the gut, called Prevotella histicola, prevented multiple sclerosis from developing in a preclinical mouse model, found researchers at the Mayo Clinic in Rochester, Minnesota, along with colleagues at the University of Iowa. Current research suggests that alterations to the gut microbiome residing in human intestines may potentially trigger inflammatory diseases such as MS. In an attempt to identify which gut resident bacteria are capable of modulating immune responses, researchers studied cultured small pieces of intestine tissue extracted from biopsies of patients with celiac disease. The team then isolated three bacteria strains and found that one of species — P. histicola — had the capacity to suppress MS in a preclinical animal model of the disease. “This is an early discovery but an avenue that bears further study," Dr. Joseph Murray, a Mayo Clinic gastroenterologist and the study's lead author, said in a press release. "If we can use the microbes already in the human body to treat human disease beyond the gut itself, we may be onto a new era of medicine. We are talking about bugs as drugs." By investigating how P. histicola modulated immune responses to suppress MS, researchers found that bacteria decreased the expression of two pro-inflammatory cytokines – interferon-gamma and interleukin (IL)-17. Overall results show that P. histicola has immune modulatory activity and can suppress abnormal immune responses, which ultimately prevent autoimmunity. This supports the idea that maintaining a healthy microbial community within our intestines is a potential therapeutic strategy for MS. "Our work is a classic example of a bedside-to-bench and potentially back to bedside study. Recent MS microbiome studies have shown the lack of Prevotella genus in patients with the disease and an increase when patients were treated with disease-modifying drugs," said Ashutosh Mangalam, the study's first author and an assistant professor of pathology at University of Iowa's Carver College of Medicine. "And it's not just for MS, because this may have a similar modulating effect on other nervous system and autoimmune diseases."

Children with multiple sclerosis consume less iron, which may affect their immune and nervous systems, according to a study. Most MS cases occur between the ages of 20 and 40, but sometimes children under 18 develop it. Pediatric-onset MS, as it is called, is believed to account for 3 to 5 percent of cases that adults have now. Despite their low frequency, they are important because "the study of factors early in life which could affect their disease may provide important insight into the disease more generally," the researchers from the Network of Pediatric MS Centers wrote. One of the factors that could be important in the onset of MS is diet. But little has been known about how diet influences the risk and progression of the disease, particularly in pediatric MS. In a study funded by the National MS Society, researchers decided to investigate the association between diet and MS in children, according to a press release. The team recruited 312 MS patients 18 and younger from 16 children's hospitals in the United States, and 456 controls without MS. The participants, or their parents, answered a questionnaire dealing with the participants' medical history, their physical development, and whether they were exposed to potentially harmful environmental factors. The questionnaire also covered demographic information and race. Researchers used the Block Kids Food Screener questionnaire to obtain information about the participants' diets, including their intake of fiber, fat, carbohydrates, proteins, fruits, vegetables, dairy products, and iron. The analysis showed no meaningful link between the consumption of fiber, fat, carbohydrates, proteins, fruits, vegetables, and dairy products and children's development of MS. Children with the disease did have lower iron intake than the controls, however. Although in this exploratory study researchers didn’t look at whether there was a cause-and-effect relationship between iron and MS, the results suggested that children with the disease may be less likely to consume iron, a fact that warrants further investigation. Iron is a vital mineral for our body to function properly, and low iron intake may affect the immune and nervous systems. Future studies on the risk of children developing MS should "investigate the role of specific vitamins and minerals," the team said. They should also "investigate the influence of dietary factors on disease outcomes in already established" cases of MS.

First-line treatment with Copaxone (glatiramer acetate) benefits relapsing-remitting multiple sclerosis (RRMS) patients by boosting the number of anti-inflammatory immune cells and restoring the balance of regulatory immune cells, an Italian study shows. The study, “Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10…

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…

A gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases like multiple sclerosis, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) report. It's a discovery that, they said, appears to be "a big step in the right direction." According to the study, published in the journal Science Immunology, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. “We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” Ciriaco Piccirillo, the study's lead author and an immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release. Tregs are known to be the immune system players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions. The FOXP3 gene is also well-known, and documented, to be essential for proper Treg cell function. However, the mechanisms by which FOXP3 gene is involved in Treg cell activities are still poorly understood. In the study, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions,” the research team — in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan — evaluated the impact of a FOXP3 gene mutation in autoimmunity response. Taking advantage of cutting-edge technology, the team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. “What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” said Piccirillo. “Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” added Khalid Bin Dhuban, the study's first author and a postdoctoral fellow in Piccirillo’s laboratory. The team developed a compound capable of restoring Treg cells' ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, two chronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including multiple sclerosis, type 1 diabetes, and lupus. "Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," said Piccirillo. “Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.” “This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Piccirillo added. “With this discovery, we are taking a big step in the right direction.”

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…

Researchers managed to retrain the immune system to ignore antigens that trigger an autoimmune reaction. This approach alleviated the symptoms of multiple sclerosis (MS) and type 1 diabetes in a mouse model.

Sex hormones, and genes in the two sex chromosomes, impact the risk of multiple sclerosis (MS) in men and women differently, and lead to differences in the course of the disease between the sexes, according to two studies. Two speakers at the ACTRIMS 2017 Forum highlighted the role of sex…

Lately, I have been reading more and more about the potential connection between the blood brain barrier and multiple sclerosis. I have been researching the blood brain barrier (BBB) to better understand it and share my findings with readers. The BBB is a network of endothelial cells…

A variant in the TYK2 gene, which encodes an immune system protein, may work to protect people from autoimmune disorders, including multiple sclerosis (MS), without overly depressing the body’s ability to fight opportunistic infections, researchers at the University of Oxford report. Their study, “Resolving TYK2 Locus Genotype-To-Phenotype Differences In Autoimmunity,” was published…

Researchers have discovered that a type of immune molecule — called “spliced epitopes,” once believed to be very rare  — in fact makes up a large part of the molecules labeling cells as belonging to the body, and those that are invaders. The finding may well change our understanding of multiple…

A genome-wide analysis of over 110,000 people allowed researchers with the International Multiple Sclerosis Genetics Consortium (IMSGC) to discover 200 genetic loci (the position of genes on a chromosome) that are common to people with multiple sclerosis (MS). The findings were given in the presentation, “200 loci complete the genetic puzzle of multiple sclerosis,” by Dr. Nikolaos…

In multiple sclerosis (MS), scientists have long believed that the body’s own immune system attacked myelin sheaths, the “insulating tape” that surrounds neurons, causing the disease. But researchers at Tel Aviv University are challenging that view, in a study reporting that MS may in fact be triggered by an instability inherent in the myelin membranes. The…

A newly discovered potential biomarker of multiple sclerosis (MS) may help to distinguish between people who will go on to have less severe disease and those in whom the disease will progress, researchers at Linköping University in Sweden report. The biomarker’s discovery came through an investigation into the immune system of MS…

Multiple sclerosis patients are at risk of developing lymphopenia, or abnormally low levels of immune defense white blood cells, called lymphocytes, according to a study that investigated lymphocyte counts in people with relapsing MS both before and after the start of treatment. The study, “Lymphopenia in treatment-naive relapsing multiple…

Gut bacteria and health have been topics of considerable scientific speculation in recent years, and the field of multiple sclerosis (MS) research is no exception. But what do we really know about MS and our intestinal inhabitants? A review, “Emerging Concepts on the Gut Microbiome and Multiple Sclerosis,” published in…

Fecal samples from a group of people with relapsing-remitting multiple sclerosis (RRMS) showed evidence of a different gut microbiota than that found in healthy controls, and may be a non-genetic reason for the altered immune system responses seen in MS patients. The study, “Multiple sclerosis patients have…

One of the world’s most commonly used medications — the cholesterol-lowering drug simvastatin — was found to affect the immune system in a way that can be explored to treat inflammatory diseases such as multiple sclerosis (MS). Researchers have earlier noted that simvastatin, a cholesterol-lowering drug, is beneficial for MS…

An immunologist at Victoria University of Wellington is leading a clinical trial that will use existing drugs in a new way to try to treat secondary progressive multiple sclerosis (SPMS), a disease form that affects more than one-third of all multiple sclerosis patients but has no effective treatment options. Anne La Flamme, a professor…

Researchers investigating immune B-cell response to the Epstein-Barr virus (EBV) and cytomegalovirus (CMV) found that it may correlate with the amount of brain-specific B-cells in the blood — a marker of multiple sclerosis (MS) — and with higher disease activity. The findings were published in the journal Viruses, in…

A commonly prescribed multiple sclerosis (MS) medication may act to modulate the immune system. The finding is described in the article “Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2,“ published in  the journal Proceedings of the National Academy of Sciences. MS develops due to an…

The immune system-suppressing multiple sclerosis (MS) drug fingolimod (Gilenya) also has potentially beneficial effects on the nervous system, according to a recent study, “The multiple sclerosis drug fingolimod (FTY720) stimulates neuronal gene expression, axonal growth and regeneration.“  The article appeared online March 12 in an early version of the journal …

Clinical trials suggest that hematopoietic stem cell transplantation (HSCT), a common treatment for bone marrow and blood cancers, could also help people with multiple sclerosis (MS). The technique involves harvesting new, undeveloped blood or bone marrow (hematopoietic) cells, typically from the person affected with the disease (autologous). The goal is to…

A recent BBC Panorama program titled “Can you stop my Multiple Sclerosis?” featured a ground-breaking treatment for select patients with multiple sclerosis (MS) that has been developed at Sheffield Teaching Hospitals in the United Kingdom. The program tells the stories of four patients, each with a diagnosis of relapsing-remitting MS (RRMS), who underwent the…

Researchers are proposing for a first time that multiple sclerosis (MS) is triggered by the death of a specific cell population within the central nervous system called oligodendrocytes. The study, titled “Oligodendrocyte death results in immune-mediated CNS demyelination,” was published in the journal Nature Neuroscience. Oligodendrocytes,…