Learn more about the best foods for autoimmune conditions and what you should avoid if you have an autoimmune disease.
autoimmune conditions
A recent study has uncovered the molecular mechanism responsible for multiple sclerosis (MS) and other autoimmune diseases.
Over twenty years ago, a research team in the lab of David Hafler, a Yale researcher who was at Harvard at the time, identified a type of T cell in humans that suppresses the immune system. Later, they discovered that these regulatory T cells, when not functioning properly, are a root cause of autoimmune diseases, such as multiple sclerosis (MS). However, the exact mechanism behind this malfunction has remained unclear for many years.
In a recent study led by Yale University, a team of researchers discovered that the loss of immune regulation is caused by an increase in PRDM1-S, a protein involved in immune function. This increase triggers a complex interaction of multiple genetic and environmental factors, such as high salt intake.
The findings, which were published in the journal Science Translational Medicine, also reveal a new target for a universal treatment for human autoimmune diseases.
“These experiments reveal a key underlying mechanism for the loss of immune regulation in MS and likely other autoimmune diseases,” said Hafler, who is also the chair of Yale’s Department of Neurology. “They also provide mechanistic insight into how Treg (regulatory T cells) dysfunction occurs in human autoimmune diseases.”
Autoimmune diseases, common among young adults, are influenced by genetic and environmental factors such as vitamin D deficiency and fatty acids. Sumida and Hafler found that high salt levels contribute to multiple sclerosis development by inducing inflammation in CD4 T cells and causing loss of regulatory T cell function, mediated by a salt-sensitive kinase called SGK-1.e,
“Tiny Killers: How Autoantibodies Attack the Heart in Lupus Patients”
Autoantibodies attacking the heart in lupus patients Credit Hand-drawn image by Xiaokan Zhang/Vunkak-Novakovic Lab
Cardiovascular disease is the primary cause of death in individuals with lupus, an autoimmune disease that occurs when the immune system attacks the body’s own tissues and organs, including the heart, blood, lungs, joints, brain, and skin. Lupus myocarditis, inflammation of the heart muscle, can be extremely serious as it can disrupt the normal rhythm and strength of the heartbeat. However, understanding the mechanisms of this complex disease is challenging and studying it is difficult.
A long-standing question about lupus is why some patients develop myocarditis while others remain unaffected, and why the clinical manifestations of affected patients range so dramatically, from no symptoms at all to severe heart failure. Lupus is characterized by a large number of autoantibodies, which are immune proteins that mistakenly target a person’s own tissues or organs, with different specificities for various molecules. These autoantibodies, similar to our genes, may explain why different individuals experience different symptoms.
Researchers have long suspected that certain autoantibody signatures may be the key to understanding the varied clinical presentations seen in lupus patients. Identifying the specific autoantibodies responsible for heart damage has been very difficult due to the lack of experimental models that accurately mimic the cardiac disease in lupus patients. The animal models currently used have limitations due to differences in cardiac physiology, and human cell cultures are unable to fully replicate the complexity and function of the human heart.
New study shows that autoantibodies can directly affect heart disease in lupus patient
The researchers created small cardiac tissues from healthy adult human stem cells, and then they matured the tissues using metabolic and electromechanical signals. Afterward, they exposed the tissues to the autoantibodies present in the blood of lupus patients who had myocarditis and those who did not. The team found that the way the patients’ autoantibodies attached to the heart tissue depended on the type and severity of their myocardial damage. Some patients with severe myocarditis had unique autoantibodies that mainly targeted dying cardiac cells, while those with weakened heart pump function had autoantibodies that mostly focused on the surface of live cells. Interestingly, the team also found that the autoantibodies binding to live cardiac cells could have powerful biological effects on the tissues without the presence of immune cells, potentially revealing new mechanisms that could lead to heart failure in lupus patients.
The study also identified four autoantibodies that may directly affect the heart muscle. These findings could assist in identifying lupus patients with the highest risk of developing heart disease, informing the development of new therapeutic strategies, and potentially extending to other autoimmune diseases.
“This study is the first to show that autoantibodies can directly cause injury to the heart in this complicated autoimmune disease,” said Gordana Vunjak-Novakovic, the leader of the team. She is the University Professor and the Mikati Foundation Professor of Biomedical Engineering, Medical Sciences, and Dental Medicine at Columbia. “It’s astonishing that the miniature heart tissues we’ve created using human stem cells and ‘organs-on-chip’ technology can replicate organ-level functions in a way that is specific to each patient, particularly for such a complex disease. We are now in an era where we can examine the progression and treatment of diseases using seemingly simple yet highly controllable and predictive models of human organs. It feels like we are living in the future.”
“Tiny particles could be used to deliver therapeutics that prevent diabetes.”
Inside each of us, there is a group of cells that work to protect us from outside germs and internal dangers like cancer. However, these cells can sometimes mistakenly attack the body, leading to autoimmune diseases such as type 1 diabetes.
Texas A&M researchers have recently been awarded an RO1 grant from the National Institutes of Health. The grant is intended to support the development of a strategy to deliver immune-suppressing proteins that are typically produced by specialized stem cells. This approach has the potential to reduce the immune system’s attack on the insulin-producing beta-cells in the pancreas, paving the way for a new treatment for type 1 diabetes.
“We are thrilled that the NIH will support our research in this area, which has implications not only for type 1 diabetes but also for other autoimmune diseases,” said Dr. Roland Kaunas, associate professor in the biomedical engineering department and recipient of the grant award.
The National Diabetes Statistics Report states that 35 out of 10,000 youths in the United States have diabetes, with 304,000 of them having type 1 diabetes. Currently, the only approved treatment for this condition is lifelong insulin therapy. However, ongoing research is exploring new therapeutics and approaches for treating this and other autoimmune diseases. For instance, cell-based therapies, where immune cells or stem cells are genetically modified to produce immune-suppressing substances, are being actively investigated. Nevertheless, these interventions face challenges such as toxicity and difficulties in transplanting gene-edited cells.
“Mēsĕnchȳmal stem cells are valuable as a therapy because they can dampen the immune response. However, they are not FDA approved,” said Kaunas. “This is a strong motivation for developing cell-free versions of stem cell therapies that could represent a lower hurdle to getting approval by the FDA.”
TAMU researchers have focused on delivering therapeutic products produced by stem cells, rather than the cells themselves. For example, mesenchymal stem cells (MSCs) produce extracellular vesicles – tiny cargo-carrying packets containing RNA, DNA, and other proteins. Some of these proteins, such as cytokines and chemokines, can reduce immune activity. Dr. Ryang Hwa Lee, the principal investigator and associate professor at the Texas A&M School of Medicine, has previously shown the therapeutic potential of both MSCs and the extracellular vesicles they produce in preclinical models.
Lee and Kaunas are currently researching whether extracellular vesicles can be modified to deliver extra immune-suppressing proteins, with the goal of better preventing the immune system from attacking insulin-producing beta-cells. They also aim to show whether these modified extracellular vesicles can stop or even reverse the development of type 1 diabetes. Lastly, the team plans to study how the modified EVs, in combination with existing immune therapies, can work together to suppress the immune system.
“We hope that our research will lead to an additional therapeutic avenue that can improve the efficacy and safety of existing immune therapy for type 1 diabetes,” said Lee. “Although ours is preclinical work, its success will facilitate the development of robust and ready-to-use extracellular vesicle-based therapeutics for type 1 diabetes and other autoimmune diseases.”
“An engineered probiotic has been developed to treat multiple sclerosis.”
Brigham researchers are developing a new method to target autoimmune reactions in the brain using designer bacteria, aiming to make treatments safer and more effective.
Researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have developed a probiotic to suppress autoimmunity in the brain. This occurs when the immune system attacks the cells of the central nervous system and is at the core of several diseases, including multiple sclerosis. In a new study, researchers demonstrated the treatment’s potential using preclinical models of these diseases. They found that the technique offers a more precise way to target brain inflammation with reduced negative side effects compared to standard therapies. T
“Engineered probiotics could revolutionize the way we treat chronic diseases,” said lead author Francisco Quintana, PhD, of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital. “When a drug is taken, its concentration in the bloodstream peaks after the initial dose, but then its levels go down. However, suppose we can use living microbes to produce medicine from within the body. In that case, they can keep producing the active compound as it’s needed, which is essential when we consider lifelong diseases that require constant treatment.”
Autoimmune diseases impact around 5-8% of the U.S. population. Despite being widespread, there are limited treatment options for most of these diseases. Diseases like MS that affect the brain are especially difficult to treat because many medications can’t effectively reach the brain due to the blood-brain barrier, which acts as a protective barrier between the brain and the circulatory system.
In their search for new treatments for autoimmune diseases, researchers focused on dendritic cells, a type of immune cell found in high numbers in the gastrointestinal tract and around the brain. While these cells regulate the immune system, their specific involvement in autoimmune diseases is not yet fully understood. Through their study of dendritic cells in the central nervous system of mice, the researchers identified a biochemical pathway that these cells use to inhibit other immune cells from attacking the body.
“The mechanism we discovered acts like a brake for the immune system,” explained Quintana. “In most people, it is activated. However, in individuals with autoimmune diseases, there are issues with this braking system, which means the body lacks a way to defend itself from its own immune system.”
The researchers discovered that this biochemical brake can be activated with lactate, a molecule involved in numerous metabolic processes. Then, they successfully genetically engineered probiotic bacteria to produce lactate.
“Probiotics are not new – we have all seen them sold as supplements and marketed as a way to promote health,” said Quintana. “Using synthetic biology to get probiotic bacteria to produce specific compounds relevant to diseases, we can enhance the benefits of probiotics to the maximum.” They tested their probiotic in mice with a disease closely resembling MS and found that, even though the bacteria live in the gut, they could reduce the disease’s effects in the brain. They did not find the bacteria in the bloodstream of the mice, suggesting that the observed effect resulted from biochemical signalling between cells in the gut and in the brain.
“We have discovered in recent years that the microorganisms in the gut have a significant impact on the central nervous system,” said Quintana. “We focused on multiple sclerosis in this study to see if we can use this effect to treat autoimmune diseases of the brain. The results indicate that we can.” Although the current study only looked at the effect of the probiotic in mice, the researchers are optimistic that the approach could be easily adapted for human use because the strain of bacteria used to create the probiotic has already been tested in humans. The researchers are also working to adjust their approach for autoimmune diseases that affect other parts of the body, especially gastrointestinal diseases like inflammatory bowel syndrome.
Quintana and his colleagues are collaborating with Mass General Brigham Ventures to establish a new company. Mass General Brigham is renowned for its leadership in research and innovation, which has led to the formation of numerous companies driving scientific advancement and economic growth locally and globally. These companies allow patients worldwide to benefit from the discoveries made at Mass General Brigham. Quintana stated, “Using living cells as a form of medicine within the body holds great potential for creating more personalized and precise therapies. If the microbes in the gut can impact brain inflammation, we believe we can harness their power for other applications.”