Tag: autoimmune disease

Categories : Medical Research & TechnologyTags :

New Type of Skin Cell Reveals Secrets of Inflammation

On By ModernMedia

The surprise discovery of a new type of cell explains how distress to the skin early in life may prime a person for inflammatory skin disease later, according to a new study in Nature. This finding will likely lead to treatments for autoimmune disorders like scleroderma, and inform understanding of inflammatory disease.

“The results reinforce the idea that what you’re exposed to initially may have lasting ramifications,” said lead researcher Michael Rosenblum, MD, PhD. “It appears that early exposure to inflammation can, through these cells we discovered, imprint an ability for tissues to develop inflammatory disease later in life.”

The team came across this new type of cell while investigating the effects of certain actions known to evoke immune response in mice. One of these actions involved knocking out a group of skin cells that suppress the immune system. Without that regulation, said Dr Rosenblum, a unique cell was observed that seemed to act as a shelter for pathogenic immune cells not typically seen in skin tissues.

“We had to knock out one cell population to see that they were controlling the growth and capacity of these other, unknown cells,” he said, noting that the new cells only became apparent in the tissue exposed to inflammatory triggers. “What normally would be a deserted island on the skin was now inhabited by all these strangers,” he said.

The team dubbed these strangers ‘TIFFs’ (Th2-interacting fascial fibroblasts) after the Th2 immune cells that they help to house. The location of TIFFs in the skin suggests that they belong to a group of cells that make up the fibrous connective tissue that is fascia, said lead author Ian Boothby, a graduate student in Dr Rosenblum’s lab.

“Because most organs have fascia of some sort, what we’re learning about TIFFs in skin may well be widely applicable to the rest of the body, meaning that these cells may play a role in a huge number of inflammatory diseases,” he said.

Boothby and Dr Rosenblum when skin without regulatory cells receives inflammatory triggers, the TIFFs spread like wildfire and become a sort of holding pen for the Th2 immune cells. Later in life, when there is even a small insult to the skin, Dr Rosenblum said, the TIFFs open their floodgates, unleashing the Th2 cells.

It seems that, through these cells, early exposure to inflammalation can leave a life-long imprint.

“All you need to do is push the immune system just a little bit, with a wound or with stress, to unleash all the pathogenic cells living in these TIFFs and create an exaggerated inflammatory response,” he said.

The researchers hypothesise that the exaggerated response may manifest as the creation of fibroses in the fascia, the driving force behind inflammatory skin diseases such as scleroderma.

To confirm the presence of TIFFs in human skin, the team obtained samples from volunteers with eosinophilic fasciitis (EF), a rare inflammatory disorder in which eosinophils build up in the skin fascia, the fibrous tissue between the skin and the muscles below it.

Comparing the EF samples to those of healthy skin, the researchers found TIFFs in both, but looked completely different. In healthy skin, the fascia forms a thin, spidery network between fat cells, while in the EF skin sample, the cells had expanded to form thick bands of fibrous tissue.

Revealing the mysteries of inflammation
TIFFs appear to be present in every organ, said Dr Rosenblum, usually found in the fascia surrounding major organs and serve a role in maintaining structure. They’re also prone to interacting with immune cells. He postulates that TIFFs might have evolved as a sort of emergency brigade in case of injury, able to jump-start repair in the case of internal injury.

“In patients with scleroderma or other fibrosing diseases like EF, that repair program may be kind of co-opted, resulting in this chronic wound-healing response,” said Dr Rosenblum. “If we can understand the biology of these cells, we can come in with drugs that revert them back to what they’re supposed to be doing.”

Source: University of California San Francisco

Categories : Immune SystemTags :

Autoimmune Problems May Cause Fibromyalgia

On By ModernMedia
Photo by Sasun Bughdaryan on Unsplash

New research has shown that many fibromyalgia syndrome (FMS) symptoms are caused by antibodies that increase the activity of pain-sensing nerves throughout the body.

The results show that fibromyalgia is a disease of the immune system, rather than the currently held view that it originates in the brain.

Characterised by widespread muskoleskeletal pain, as well as fatigue and emotional distress, fibromyalgia is estimated to affect1 in 40 people (80% of which are women). It most commonly develops between the ages of 25 and 55, although children can also get it.  

The study by Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, in collaboration with the University of Liverpool and the Karolinska Institute,, demonstrates that the increased pain sensitivity, muscle weakness, reduced movement, and reduced number of small nerve-fibres in the skin that are typical of FMS are all a consequence of patient antibodies.

The researchers injected mice with antibodies from people living with FMS and saw that the mice became more sensitive to pressure and cold, as well as displaying reduced movement grip strength. In contrast, those injected with antibodies from healthy people were unaffected, showing that patient antibodies cause at least part of the disease.

Furthermore, the mice injected with fibromyalgia antibodies recovered after a few weeks, when antibodies had been cleared from their system. This finding strongly suggests that therapies which reduce antibody levels in patients are likely to be effective treatments. Such therapies are already available and are used to treat other disorders that are caused by autoantibodies.

Primary investigator Dr David Andersson, from King’s IoPPN said: “The implications of this study are profound. Establishing that fibromyalgia is an autoimmune disorder will transform how we view the condition and should pave the way for more effective treatments for the millions of people affected. Our work has uncovered a whole new area of therapeutic options and should give real hope to fibromyalgia patients.

“Previous exploration of therapies has been hampered by our limited understanding of the illness. This should now change. Treatment for FMS is focussed on gentle aerobic exercises, as well as drug and psychological therapies designed to manage pain, although these have proven ineffective in most patients and have left behind an enormous unmet clinical need.”

Dr. Andreas Goebel, the study’s principle clinical investigator from the University of Liverpool said, “When I initiated this study in the UK, I expected that some fibromyalgia cases may be autoimmune. But David’s team have discovered pain-causing antibodies in each recruited patient. The results offer amazing hope that the invisible, devastating symptoms of fibromyalgia will become treatable.”

Professor Camilla Svensson, the study’s primary investigator from Karolinska Institute said, “Antibodies from people with FMS living in two different countries, the UK and Sweden, gave similar results, which adds enormous strength to our findings. The next step will be to identify what factors the symptom-inducing antibodies bind to. This will help us not only in terms of developing novel treatment strategies for FMS, but also of blood-based tests for diagnosis, which are missing today.

Dr Craig Bullock, Research Discovery and Innovations Lead at Versus Arthritis said: “This research shows that antibodies found in human blood can cause fibromyalgia-like symptoms in mice, suggesting that these antibodies play a crucial role in the condition. Further research is needed but this offers hope to the millions of people with fibromyalgia that an effective treatment could be found in the relatively near future.”  

Source: Medical Xpress

Journal information: More information: Andreas Goebel et al, Passive transfer of fibromyalgia symptoms from patients to mice, Journal of Clinical Investigation (2021). DOI: 10.1172/JCI144201

Categories : Immune SystemTags :

Newly Discovered ‘Goldilocks’ Protein Keeps the Immune System in Check

On By ModernMedia

A newly discovered ‘Goldilocks’ protein may be responsible for helping keep the immune system from running amok, according to researchers at the Lunenfeld-Tanenbaum Research Institute (LTRI).

This protein, known as WAVE2, is expressed in all immune cells and plays a critical role in keeping the immune system in balance. To test its role, researchers knocked out the WAVE2 protein in a subset of immune cells in mice, leading to severe autoimmunity and inflammation, as well as an inability to mount an immune response to a viral infection.

Senior author Dr Kathy Siminovitch, said the team also found that in the absence of WAVE2, another protein, known as mTOR, became overly active, sending the immune system into overdrive and leading to immune cell exhaustion.

“Much like Goldilocks, a proper immune response requires such a delicate balance,” said Dr  Siminovitch. “You have to get it just right. By developing a mouse strain in which T cells, key players in immunity, lack WAVE2, we have shown that this protein is absolutely required for balanced immune responses.”

The question of how to keep the immune system in balance is of key importance in the pandemic, where many deaths occur due to cytokine storms as the immune system overreacts, especially in the elderly. 
As part of her work exploring the mechanisms balancing the immune system, Dr Siminovitch helped trace the complex molecular steps that turn a rare gene mutation into Wiskott-Aldrich syndrome, a potentially lethal disease which impairs the immune system of boys.

Future research would look at how the contribution of the WAVE2-mTOR pathway to specific autoimmune, inflammatory and other conditions, such as Alzheimer’s disease.

Source: News-Medical.Net

Journal information: Liu, M., et al. (2021) WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity. Science. doi.org10.1126/science.aaz4544.

Categories : Diseases, Syndromes and Conditions T-cellsTags :

Ginger Promising in Countering Autoimmune Diseases

On By ModernMedia

A pre-clinical study has shown that the common herbal remedy and condiment, ginger, may be effective in countering some autoimmune disease mechanisms.

It is already known that ginger has some anti-inflammatory and anti-oxidative properties, making it a popular herbal remedy for inflammatory conditions.Out of at least 14 bioactive compounds, 6-gingerol, which also gives it its distinctive aroma and taste, is reported by a news study to be therapeutic in countering certain autoimmune disease mechanisms in mice.
In mice with antiphospholipid syndrome or lupus, 6-gingerol inhibited the release of neutrophil extracellular traps, which is triggered in response to the autoantibodies produced by these diseases. 

“Neutrophil extracellular traps, or NETs, come from white blood cells called neutrophils,” said lead author Ramadan Ali, PhD. “These sticky spider-web like structures are formed when autoantibodies interact with receptors on the neutrophil’s surface.”

According to Ali, these webs play an important role in the pathogenesis of lupus and antiphospholipid syndrome where they trigger autoantibody formation and contribute to blood vessel clotting and damage.

The premise of the study was: “Will the anti-inflammatory properties of ginger extend to neutrophils, and specifically, can this natural medicine stop neutrophils from making NETs that contribute to disease progression?”
“This pre-clinical study in mice offers a surprising and exciting, ‘yes’,” Ali said.

The researchers discovered that after giving 6-gingerol, the mice had lower levels of NETs. Clot formation tendency was drastically reduced and 6-gingerol seemed to inhibit neutrophil enzymes called phosphodiesterases, in turn lowering neutrophil activation.

All of the mice had reduced autoantibodies, suggesting a disruption of the inflammatory cycle of autoantibodies stimulating NETs which stimulate more autoantibodies.

Study author and rheumatologist Jason Knight, MD, noted that patients often asked about herbal supplements, about which he had not been taught much. However, the pre-clinical trial results show that 6-gingerol has anti-neutrophil properties that may be protective against autoimmune disease progression.

“As for basically all treatments in our field, one size does not fit all. But, I wonder if there is a subgroup of autoimmune patients with hyperactive neutrophils who might benefit from increased intake of 6-gingerol,” said Knight. “It will be important to study neutrophils before and after treatment so we can determine the subgroup most likely to see benefit.”
For a patient with active antiphospholipid syndrome or lupus, the bioactive compound cannot be the primary therapy, but the natural supplement may help those at high risk for disease development.

“Those that have autoantibodies, but don’t have activated disease, may benefit from this treatment if 6-gingerol proves to be a protective agent in humans as it does in mice,” Ali said.

“Patients with active disease take blood thinners, but what if there was also a natural supplement that helped reduce the amount of clots they produce? And what if we could decrease their autoantibodies?”

Source: Medical Xpress

Journal Information: Ramadan A. Ali et al, Anti-neutrophil properties of natural gingerols in models of lupus, JCI Insight (2020). DOI: 10.1172/jci.insight.138385

Categories : Diseases, Syndromes and ConditionsTags :

Promising Drug May Worsen Instead of Treat Multiple Sclerosis

On By ModernMedia

A drug, TEPP-46,  that is being assessed to treat multiple sclerosis (MS) may in fact be worsening the progression of the disease, wrote University of Virginia on the Medical Xpress website.

MS is a debilitating disease which affects over one million people in America, in which the immune system attacks the myelin sheath, creating a range of effects in sufferers, from muscle spasms to numbness.

Presently available drugs to treat MS often have unwanted side effects, such as weakening the immune system. Originally developed to fight cancer, TEPP-46 is small-molecule drug that targets the changes in cellular metabolism that occur in both cancer and MS. However, the drug has been shown to produce off-target effects. In the mouse model used by the researchers, the inflammation was directed away from the spinal cord and into the brain. The researchers believed that this was the result of the drug harmfully changing T cells, but could not explain why. 

“It was not at all what we expected,” said MS researcher Alban Gaultier, PhD, of University of Virginia. “The take-home message is that we should be very careful and do more fundamental research before we propose to take this to clinical trials.”