Causes

When the following headline in the Australian newspaper the Herald Sun caught my eye recently, I was cautiously intrigued: “Doctors believe they have discovered the cause of multiple sclerosis” My cynical heart didn’t go pitter-patter as…

Long-term exposure to three common air pollutants — fine particulate matter, nitrogen dioxide, and ozone — were not found to be “convincingly” linked to incidence of multiple sclerosis (MS) in a large population study conducted in Canada. The study, “Long-term exposure to air pollution and the incidence of multiple sclerosis: A…

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).

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…

Exposure to epsilon toxin (ETX), which is mainly found in livestock, could be linked to the development of multiple sclerosis (MS), new research suggests. The study, “Evidence of Clostridium perfringens epsilon toxin associated with multiple sclerosis,” appeared in the Multiple Sclerosis Journal. ETX is one of…

Editor’s note: To learn more about the link between the Epstein-Barr virus and MS, read Ed’s May 2020 column titled “More Evidence Links Epstein-Barr Virus to MS.” For years researchers have believed a link exists between the Epstein-Barr virus (EBV) and multiple sclerosis. But scientists have had…

People who live in areas with medium to high levels of ultraviolet-B (UV-B) radiation from sunlight during their childhood and early adolescence, or in the years preceding the age of onset of multiple sclerosis (MS), have a lower risk of developing the disease, according to researchers. The study’s findings…

United Arab Emirates scientists have found active Epstein-Barr virus in many multiple sclerosis patients’ brain cells, supporting the notion that it plays a role in the disease. The team found it in two types of brain cells — astrocytes and microglia. The virus can be active or lie dormant in…

A molecule triggered by the male hormone testosterone protects male mice from developing multiple sclerosis, Northwestern Medicine researchers report. Their discovery may help explain why MS affects more women than men. It could also lead to targeted therapies to protect women against the disease. The study, “…

Iranian researchers have identified another herpes virus that may increase the risk of a person developing multiple sclerosis. The team identified the human herpesvirus 6, or HHV6, as a potential risk factor for MS through a meta-analysis of several studies. They published their findings, “Relationship of Human…

A large U.K. survey assessing the frequency of chickenpox and shingles in multiple sclerosis (MS) patients suggests a link between these diseases and MS, researchers report, suggesting their findings could help in decisions regarding immunosuppressive treatments and varicella-zoster virus vaccinations. Results of the study “Prevalence of a history of…

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…

The discovery of an immune cell quality control mission may have put scientists a step closer to understanding how autoimmune conditions such as multiple sclerosis arise. University of Alabama at Birmingham researchers identified regulatory immune cells with the quality control mission of destroying antibody-producing B-cells that mistakenly target the body's own tissue after an infection. An autoimmune disease is one in which the immune system attacks healthy tissue or organs instead of invaders. Eventually, the insight could lead researchers to new approaches for treating MS and other conditions caused by aberrant immune reactions. The Alabama researchers were studying the processes involved in the body's defense against a real threat — the influenza virus — when they discovered a population of immune cells whose action is relevant to autoimmune diseases. The study noted that T follicular regulatory cells appeared in the late stages of influenza infection. Their objective was to prevent the immune system from generating self-reactive antibodies — that is, those that attack the body's own tissue. These cells are poorly understood, the researchers explained. Their experiments, published in the journal Nature Immunology, focused on the molecular events surrounding the cells’ actions.  The team discovered that about a week after the infection, levels of an immune regulator called the IL-2 protein increased. This triggered the multiplication of common regulatory T-cells, or Tregs. When this phase of the immune reaction was fading, TFR cells started multiplying, reaching peak numbers about a month after infection. The formation of the TFR cells was therefore tightly linked to the processes controlling Treg production, researchers said, with falling levels of IL-2 allowing the new phase of the immune response. The TFR cells migrated to the lymph nodes — the headquarters of antibody-producing B-cells. Here, B-cells proliferate and change their antibody-producing genes to create new, stronger antibodies. But sometimes the gene changes, or mutations, give rise to an antibody that attacks the body, instead of invaders. Researchers discovered that TFR cells prevented B-cells, which gave rise to autoantibodies, from accumulating in the lymph nodes. Importantly, the TFR cells had no impact on the immune processes targeting the influenza virus. When researchers prevented TFR cells from forming or removed them from mice, the animals started producing autoantibodies, they explained. While this suggested that people with autoimmune diseases may have flawed TFR processes, the study did not investigate this, making the topic a possibility for future studies.

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.

Secondary progressive multiple sclerosis (SPMS) patients have larger quantities of certain antibodies to the stomach ulcer bacterium Helicobacter pylori than those with relapsing-remitting multiple sclerosis (RMSS), finds a Greek study which also showed that MS patients in general differ from healthy people in this aspect. Although researchers at the University of Thessaly think…

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.”

The expression by immune B-cells of a protein called T-bet is crucial to promoting production of autoantibodies that recognize and destroy the tissues of one’s own body, finds a new study by researchers at National Jewish Health in Denver. The study, “B cells expressing the transcription factor T-bet drive lupus-like autoimmunity,”…

Smoking can kill off the immune cells that commonly protect people from multiple sclerosis (MS) and other autoimmune diseases, say researchers at the University of Copenhagen — a finding that may lead to new ways of treating such illnesses. Their study, “Smoking reduces circulating CD26hiCD161hi MAIT cells in healthy…

A popular theory of what contributes to developing multiple sclerosis is a disease called mononucleosis (also known as glandular fever), which can be caused by Epstein-Barr virus (EBV). It is thought that the virus weakens our defenses in the blood-brain barrier, allowing white blood…

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…

A person unlucky enough to have two specific gene variants is at significantly higher risk of developing multiple sclerosis (MS), according to a study. The research, which gave scientists insight into the processes that cause MS, also suggested that another mutation increased the effects of a known MS risk gene. The…

A 60-year follow-up study of nearly 1,400 Norwegian patients with multiple sclerosis (MS) analyzed their survival and risk of dying starting with the onset of the disease through its progression. The study, “A 60- year follow-up on survival and cause of death in multiple sclerosis in Western Norway,” was recently…

Obesity in early adolescence poses a risk for multiple sclerosis (MS) regardless of sex, and an earlier age at puberty also contributes to MS onset at younger ages, especially in overweight teenagers, a study reports. These findings were in the study, “Distinct…

The key to why more women than men develop multiple sclerosis (MS) may be genes that influence physical traits, such as weight, height, and body shape, according to a new study. Researchers caution that the findings need to be verified, but they said processes leading to disease may differ between…

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…

Researchers have found a microbial protein from the Haemophilus influenza pathogen that is recognized by antibodies in a subpopulation of multiple sclerosis (MS) patients. The finding supports the idea of a link between microbial infections and neurodegenerative diseases like MS, whose causes are uncertain. Haemophilus influenza is an opportunistic pathogen…

The brain has a system for orchestrating a defense against viral infections, scientists report in a finding that may advance the understanding of disease processes in multiple sclerosis (MS). The newly discovered system is run by brain immune cells called microglia, and researchers will now focus on understanding how these…

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 virus known to cause respiratory infections in people — the human coronavirus (HCoV) — may also be the source of neurological diseases that strike patients, seemingly out of the blue, a new study reported. Results obtained in the study, “Human Coronavirus OC43 Associated with Fatal Encephalitis,” support the idea that diseases…

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…