Recent research has uncovered an unusual type of white blood cell that could be the main driver of autoimmunity in type 1 diabetes.New research suggests that a hybrid cell may be behind type 1 diabetes.
Many experts believe that type 1 diabetes is a type of condition that occurs when the immune system attacks the body’s own tissue.
However, although evidence from numerous studies strongly suggests that type 1 diabetes has autoimmune origins, the underlying biological mechanisms have not been clear.
The new study is the work of scientists at Johns Hopkins University School of Medicine in Baltimore, MD, and collaborators from other institutions, including the IBM Thomas J. Watson Research Center in Yorktown Heights, NY.
In a Cell paper, the authors describe how they found an “unexpected” hybrid of B and T immune cells that appears “to be involved in mediating autoimmunity.”
They discuss how the discovery breaks the “paradigm” that cells of the adaptive immune system can only be T or B cells.
The finding also challenges doubts that some scientists have cast on the idea that a “rogue hybrid” or “X cell” drives the autoimmune response behind type 1 diabetes.
“The cell we have identified,” says study co-author Abdel-Rahim A. Hamad, an associate professor of pathology at the Johns Hopkins University School of Medicine, “is a hybrid between the two primary workhorses of the adaptive immune system, B lymphocytes and T lymphocytes.”
He explains that not only did they find the so-called X cell, but that they also found “strong evidence for it being a major driver of the autoimmune response believed to cause type 1 diabetes.”
However, he cautions that their findings are not enough to prove that the hybrid cell directly causes type 1 diabetes. Further studies should now pursue this aim.
Type 1 diabetes and autoimmunity
Diabetes occurs when there is too much sugar, or glucose, in a person’s blood. In people with type 1 diabetes, this develops when the pancreas does not make enough insulin, which is the hormone that helps cells absorb and use glucose for energy.
Having too much sugar in the blood is dangerous and causes long-term damage to organs. People with type 1 diabetes have to take insulin every day.
According to the Centers for Disease Control and Prevention (CDC), around 5% of the 30.3 million people with diabetes in the United States have type 1.
Doctors used to call type 1 diabetes “juvenile diabetes” because, although it can develop at any age, it more commonly arises during childhood.
Experts believe that type 1 diabetes is an autoimmune condition wherein the immune system attacks and destroys the insulin-producing beta cells in the pancreas. However, they are not clear about the cell processes involved.
The autoimmune response relies on two types of white blood cell: B lymphocytes and T lymphocytes. Together, the two cells identify and attack entities that present a threat, such as invading bacteria, viruses, and other agents.
Each cell has its own type of cell receptor, which is a type of protein that only allows specific signals into the cell when it matches with a unique binding partner. Thus, B cells have B cell receptors (BCRs) and T cells have T cell receptors (TCRs).
Hybrid has both T and B cell receptors
The hybrid cell that Hamad and his colleagues found is a rare “dual expressor (DE)” cell that expresses working BCRs and TCRs.
The immune response usually begins when a surveillance cell called an antigen-presenting cell (APC) spots an invader and captures its signature.
The APC then travels to a reservoir, such as a lymph node, that harbors immature B and T cells and presents them with the signature, or antigen, of the invader.
Immature T cells with TCRs that match the antigen respond to the APC summons by converting into either killer or helper T cells. Killer T cells react by attacking the invader directly.
Helper T cells, however, respond by triggering immature B cells. If the B cells have the matching antigen, they make antibodies that attack and destroy the invader. If they do not, they make an imprint of the antigen so that they can mount an attack in the future.
Immune system sees insulin as the target
In autoimmune responses, however, the antigen does not identify a foreign invader, but healthy cells in the body’s own tissues. The result is a powerful attack that can wreak serious damage. In type 1 diabetes, this results in the destruction of pancreatic beta cells.
In their study paper, the authors explain that scientists do not fully understand the antigens that “drive activation of autoreactive T cells,” despite the fact that researchers have examined them “extensively.”
In the case of type 1 diabetes, scientists believe that the immune system sees insulin as the antigen.
Hamad says that scientists generally agree that T cells see insulin as the antigen “when the hormone is bound to a site on the APC known as HLA-DQ8.”
“However,” he adds, “our experiments indicate that it is a weak binding and not likely to trigger the strong immune reaction that leads to type 1 diabetes.”
He and his colleagues found that the DE cell that they discovered produces a unique protein called x-Id peptide. By means of various cell experiments, they showed that when x-Id peptide takes the place of insulin, the binding is much tighter and gives rise to an immune reaction that is 10,000 stronger.
Potential for screening and immunotherapy
Using computer simulations, the researchers at IBM Thomas J. Watson Research Center were able to pinpoint the molecular mechanism of the x-Id peptide binding. They were also able to predict how strong the T cell response would be.
The team also found that people with type 1 diabetes are more likely to have DE lymphocytes and x-Id peptide in their blood than people without diabetes.
“This finding,” Hamad argues, “combined with our conclusion that the x-Id peptide primes T cells to direct the attack on insulin-producing cells, strongly supports a connection between DE cells and type 1 diabetes.”
He suggests that, with more research, the findings could lead to the development of screening methods that can identify people with a higher risk of type 1 diabetes.
Another possibility is that the findings could lead to immunotherapies that either destroy DE cells or alter them so that they cannot trigger an autoimmune reaction.
Hamad says it is even possible that, one day, they will discover that DE cells are involved in other autoimmune illnesses such as rheumatoid arthritis and multiple sclerosis.
“What is unique about the entity we found is that it can act as both a B cell and a T cell. This probably accentuates the autoimmune response because one lymphocyte is simultaneously performing the functions that normally require the concerted actions of two.”
Abdel-Rahim A. Hamad
Vitamin D sufficiency may reduce complications of COVID-19
A recent small-scale study has concluded that hospitalized patients with COVID-19 are less likely to have life threatening complications if they have sufficient vitamin D levels.A new study demonstrates that people with sufficient levels of vitamin D are less likely to develop life threatening COVID-19 complications when hospitalized with the disease.The research, published in the…
A recent small-scale study has concluded that hospitalized patients with COVID-19 are less likely to have life threatening complications if they have sufficient vitamin D levels.A new study demonstrates that people with sufficient levels of vitamin D are less likely to develop life threatening COVID-19 complications when hospitalized with the disease.The research, published in the journal PLOS ONE, could be valuable for doctors attempting to reduce the mortality rates of COVID-19 in the absence of an effective vaccine.If further studies back up these findings, vitamin D supplements might offer a cost-effective way to limit the risk of severe COVID-19. It is important to note that this recent study has several limitations, which we address below.Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.Since the sudden emergence of the virus SARS-CoV-2 and the disease that it causes, COVID-19, scientists have paid a great deal of attention to the development of a vaccine. Experts consider a vaccine to be crucial in reducing the effects of the virus, even if it is not yet clear to what extent an initial vaccine would moderate rates of transmission and infection.Alongside the endeavor to develop a vaccine, researchers are also focusing on developing effective COVID-19 treatments. Even if none can make a person immune to the virus, treatments may be able to reduce the disease’s severity.The Food and Drug Administration (FDA) have approved two drugs as treatments for COVID-19: remdesivir and dexamethasone.Another candidate is vitamin D. Research has suggested that it might, in theory, be effective, but corroborating this requires further efforts.Rather than analyzing the effects of vitamin D as COVID-19 treatment, the researchers behind the present study looked at the effects of a person’s vitamin D levels on the severity of the disease.To do so, they analyzed data from patients with confirmed COVID-19 who had been admitted to the Sina Hospital, in Tehran, Iran.Of the 611 people admitted with confirmed COVID-19 before May 1, 2020, there were records of the 25-hydroxyvitamin D levels, an indication of overall vitamin D levels, for 235 patients. Their mean age was 58.7 years, ranging from 20–90 years, and 37.4% were older than 65.The researchers classified the patients into two groups: those with vitamin D levels of at least 30 nanograms per milliliter (ng/ml) — an amount considered sufficient by the Endocrine Society — and those with lower values.They then analyzed the severity of the patients’ COVID-19 signs and symptoms using guidelines from the Centers for Disease Control and Prevention (CDC). Severe or critical disease might involve a range of issues, including shortness of breath, respiratory failure, or a significantly reduced blood oxygen level.After cross-checking the patients’ vitamin D levels with the severity of their COVID-19 symptoms and accounting for confounding factors, the researchers found that having a vitamin D level of above 30 ng/ml was significantly associated with having less severe COVID-19.Among the 235 patients with confirmed COVID-19, only 32.8% had sufficient levels of the vitamin.The researchers also found that the patients with sufficient vitamin D had higher blood lymphocyte counts and lower levels of C-reactive protein in their blood — both of which indicate a positive immune response.The researchers speculate that this may have reduced the likelihood of developing cytokine storm, which can cause acute respiratory distress syndrome in COVID-19 patients, sometimes resulting in death.The findings highlight, the researchers say, that vitamin D sufficiency may be important in the eventuality that people develop COVID-19 alongside another respiratory disease, such as influenza.According to the study’s corresponding author, Dr. Michael F. Holick, director of the General Clinical Research Unit at the medical campus of Boston University, in Massachusetts, “There is great concern that the combination of an influenza infection and a coronal viral infection could substantially increase hospitalizations and death due to complications from these viral infections.”For the researchers, their findings suggest that vitamin D supplementation would be valuable. As Dr. Holick notes: “Because vitamin D deficiency and insufficiency is so widespread in children and adults in the United States and worldwide, especially in the winter months, it is prudent for everyone to take a vitamin D supplement to reduce [the] risk of being infected and having complications from COVID-19.”It is worthing noting the present study’s limitations. First, the researchers only had access to a relatively small number of patients. Before drawing solid conclusions, scientists need to carry out much larger studies.Also, various issues can influence both vitamin D status and COVID-19 severity, such as socioeconomic factors and smoking status. The scientists accounted for neither of these in their analysis.Also, because the study was cross-sectional, the researchers could not prove that vitamin D insufficiency caused an increase in disease severity. To address these limitations, the researchers call for “large-scale studies and randomized clinical trials.”For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.
Video gaming as a child related to improvements in memory
A new study exploring the link between video games and cognition finds that playing video games as a child can improve a person’s working memory years later on specific tasks.Video games can be a contentious topic, particularly among parents or caregivers who may be concerned about the effects of spending hours in front of the…
A new study exploring the link between video games and cognition finds that playing video games as a child can improve a person’s working memory years later on specific tasks.Video games can be a contentious topic, particularly among parents or caregivers who may be concerned about the effects of spending hours in front of the console.Yet, it seems that some video gaming could actually be beneficial. Recent studies have shown that playing video games could improve learning and may even protect against dementia in older adults.The authors of a recent review of the evidence on video games concluded that gaming could have benefits for both cognitive and emotional skills.In a new study, which features in the journal Frontiers in Human Neuroscience, researchers from the Universitat Oberta de Catalunya in Barcelona trained volunteers to play “Super Mario 64” — a game that researchers have previously shown to induce structural changes in parts of the brain associated with executive function and spatial memory.The new study found that people who played video games as children showed greater improvements in their working memory than those who did not, suggesting that video games can have long lasting benefits for cognition.This study combined video game playing with transcranial magnetic stimulation (TMS), a noninvasive form of brain stimulation that scientists have studied as a treatment for mood disorders. In 2008, the Food and Drug Administration (FDA) approved its use for the treatment of major depression when other approaches have failed.Studies have also shown TMS to boost cognitive performance under some conditions, with more than 60 studies reporting that the treatment led to significant improvements in cognition, including in working memory (holding and manipulating information over a short period).The researchers behind the new study wanted to find out whether combining video game training and TMS could enhance cognitive function more than either element alone.They asked 27 healthy volunteers, with an average age of 29 years, to take part in 10 video game training sessions, during each of which they played “Super Mario 64” for an hour and a half.At the end of each session, the researchers applied TMS to part of the prefrontal cortex, which is at the front of the brain and is important for complex cognitive functions, such as working memory and reasoning. The researchers assessed the cognitive function of the participants before the study started, at the end of the 10 sessions, and 15 days after this.They assessed a range of cognitive functions, including reaction time, working memory, attention span, visuospatial skills, and problem-solving.Although the results overall showed very limited changes in cognitive ability, which seemed to result only from the video game training and not the TMS, the researchers did find that participants with early experience of video gaming had improved working memory.“People who were avid gamers before adolescence, despite no longer playing, performed better with the working memory tasks, which require mentally holding and manipulating information to get a result,” explains lead author of the study Dr. Marc Palaus, Ph.D.People with prior experience of playing video games (but not the actual game in the study) also showed improvements in processing and were better able to focus on relevant stimuli during the tasks.“People who played regularly as children performed better from the outset in processing 3D objects, although these differences were mitigated after the period of training in video gaming, when both groups showed similar levels,” adds Dr. Palaus.The results suggest that video games may induce cognitive changes that last for years after people have stopped playing.Dr. Palaus says that video games that provide motivation — making the player want to keep on playing — and also get more difficult to stay challenging require intensive use of brain resources, which makes them ideal for boosting cognitive ability.“Video games are a perfect recipe for strengthening our cognitive skills, almost without our noticing.”– Dr. Marc Palaus, Ph.D. It is important to note that this study included a small number of participants who were all healthy, young, and highly educated, meaning that the findings might not be more widely applicable.Talking about the findings of their study, Dr. Palaus stressed that these improvements only have a limited effect on the performance of other activities not linked to video gaming, as is the case with most cognitive training.
Lax gun laws in neighboring states may increase firearm deaths
A US study suggests strong gun control regulations reduce a state’s firearm deaths, but having neighbors with more lenient laws undermines their effect.Share on PinterestNew research suggests that one state’s lax gun laws could undo the effects of its neighbor’s stricter firearm regulations.In 2017, 39,773 people died from gun-related injuries in the United States, according…
A US study suggests strong gun control regulations reduce a state’s firearm deaths, but having neighbors with more lenient laws undermines their effect.Share on PinterestNew research suggests that one state’s lax gun laws could undo the effects of its neighbor’s stricter firearm regulations.In 2017, 39,773 people died from gun-related injuries in the United States, according to the National Center for Injury Prevention and Control.Overall, research indicates that stronger state laws governing the sale and ownership of firearms reduce firearm-related deaths. However, some states have relatively high rates of gun deaths despite strict regulations. To investigate why this might be the case, scientists at the University of Alabama at Birmingham, and the Boston University School of Public Health at Boston, MA, looked into the effects of firearm laws in neighboring states.They used the Web-based Injury Statistics Query and Reporting System to obtain figures for firearm-related deaths in the 48 adjacent U.S. states from 2000 to 2017. There were 578,022 firearm deaths in total, including homicides and suicides, but excluding deaths due to shootings by police or other law enforcement agents. The scientists also searched the State Firearm Laws Database for laws in each state regarding:background checksgun dealer regulationsbuyer regulationsgun-trafficking lawsThe team used the number of these laws as a proxy for gun control strength in each state.If you would like to check your registration status or register to vote, we have added some useful links at the bottom of this article.Overall, stronger state gun laws were associated with reduced firearm deaths, but having a neighboring state with more permissive laws undermined this protective effect.Larger policy differences across state borders were associated with increased gun-related deaths, suicides, and homicides, though the results were statistically stronger for suicide than homicide.The authors conclude:“This study adds to the growing literature emphasizing the role played by neighboring states’ firearm regulations in addition to own-state firearm regulations in firearm deaths. Failing to account for neighboring states with weaker laws, in some instances, can make a state’s own regulations appear less effective in reducing firearm deaths.”The scientists calculate that, on average, failure to account for weaker firearm laws in neighboring states make it appear as though a state’s laws were about 20% less effective at reducing deaths than they really were.They report their findings in the American Journal of Preventive Medicine.The researchers write that higher prices and strong marketing regulations can lead consumers to purchase firearms in adjacent, relatively unregulated markets. They say these are a frequent source of the guns used in crimes.They believe their work supports the case for more cooperative legislation between neighboring states and at the federal level.“I think the main message of this study is that to solve a nationwide problem we need to think of a nationwide or at least a regional-level (i.e. multistate) approach, like we may also need for the COVID-19 pandemic,” says Dr. Ye Liu, who is a doctoral student in the Department of Health Care Organization and Policy at the University of Alabama and the first author of the study. “An ‘each state on its own’ approach is ultimately inadequate to address one of the biggest public health challenges in this country,” Dr. Liu adds.The authors acknowledge the number of gun-control laws may not perfectly reflect the strictness of a state’s regulations. In addition, they note states may vary in how diligently they enforce these laws.They call for further studies that might use alternative measures of regulatory strength, focus on specific categories of law, or explore the effects of regulations in more distant states. To check your voter registration status, click here to visit VoteAmerica, a nonprofit, nonpartisan organization dedicated to increasing voter turnout. They can also help you register to vote, vote by mail, request an absentee ballot, or find your polling place.