Tag: autoimmune disease

Categories : Immune System Neurodegenerative DiseasesTags :

Scientists Strengthen Evidence Linking Autoimmunity and Schizophrenia

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Links have been reported between schizophrenia and autoimmunity. In a study published in Brain Behavior and Immunity, Japanese researchers identified autoantibodies that target a ‘synaptic adhesion protein’, neurexin 1α, in a subset of patients with schizophrenia. When injected into mice, the autoantibodies caused many schizophrenia-related changes.

What is a synaptic protein, and why might it be linked to schizophrenia? Synaptic adhesion proteins are specialised proteins that bind to create physical connections between brain cells. These connections, called synapses, allow the cells to communicate by passing molecules back and forth. Both synapses and autoimmunity are known to be associated with schizophrenia, so the research team from Tokyo Medical and Dental University (TMDU) decided to investigate autoantibodies that target synaptic proteins in patients with schizophrenia.

“In around 2% of our patient population, we identified autoantibodies against the synaptic protein neurexin 1α, which is expressed by one cell in the synapse and binds to proteins known as neuroligins on the other cell in the synapse,” says lead author of the study Hiroki Shiwaku. “Once we had identified these autoantibodies, we wanted to see if they were able to cause schizophrenia-related changes.”

To do this, the researchers isolated autoantibodies from some of the patients with schizophrenia and injected them into the cerebrospinal fluid of mice, so that the autoantibodies would travel into the brain. In these mice, the autoantibodies blocked neurexin 1α and neuroligin binding and altered some related synaptic properties. The administration of these autoantibodies also resulted in fewer synapses in the brains of mice and schizophrenia-related behaviours, such as reduced social behaviour toward unfamiliar mice and reduced cognitive function.

“Together, our results strongly suggest that autoantibodies against neurexin 1α can cause schizophrenia-related changes, at least in mice,” explains Hiroki Shiwaku. “These autoantibodies may therefore represent a therapeutic target for a subset of patients with schizophrenia.”

Schizophrenia has a wide variety of both symptoms and treatment responses, and many patients have symptoms that are resistant to currently available treatment options. Therefore, the identification of possible disease-causing autoantibodies is important for improving symptom control in patients with schizophrenia. It is hoped that the results of this investigation will allow patients with autoantibodies that target neurexin 1α – all of whom were resistant to antipsychotic treatment in the present study — to better control their symptoms in the future.

Source: Tokyo Medical and Dental University

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Autoimmune Disorders Now Affect Roughly One in Ten Individuals

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A population-based study of 22 million people in the UK estimates that around one in ten individuals in the UK now live with an autoimmune disorder. The findings, published in The Lancet, also highlight important socioeconomic, seasonal and regional differences for several autoimmune disorders, providing new clues as to what factors may be involved in these conditions.

There are more than 80 known autoimmune diseases, including conditions like rheumatoid arthritis, type 1 diabetes and multiple sclerosis, some of which have been increasing in the last few decades.

This has raised the question whether overall incidence of autoimmune disorders is on the rise and what factors are involved, such as environmental factors or behavioural changes in society. The exact causes of autoimmune diseases remain largely unknown, including how much can be attributed to a genetic predisposition to disease and how much is down to exposure to environmental factors.

The study used anonymised electronic health data from 22 million individuals in the UK to investigate 19 of the most common autoimmune diseases. The authors examined whether incidence of autoimmune diseases is rising over time, who is most affected by these conditions and how different autoimmune diseases may co-exist with each other.

They found that the 19 autoimmune diseases studied affect around 10% of the population. This is higher than previous estimates, which ranged from 3–9% and often relied on smaller sample sizes and included fewer autoimmune conditions. The analysis also highlighted a higher incidence in women (13%) than men (7%).

The research discovered evidence of socioeconomic, seasonal and regional disparities for several autoimmune disorders, suggesting that these conditions are unlikely to be caused by genetic differences alone. This observation may point to the involvement of potentially modifiable risk factors such as smoking, obesity or stress. It was also found that in some cases a person with one autoimmune disease is more likely to develop a second, compared to someone without an autoimmune disease.

Dr Nathalie Conrad at the University of Oxford said: “We observed that some autoimmune diseases tended to co-occur with one another more commonly than would be expected by chance or increased surveillance alone. This could mean that some autoimmune diseases share common risk factors, such as genetic predispositions or environmental triggers. This was particularly visible among rheumatic diseases and among endocrine diseases. But this phenomenon was not generalised across all autoimmune diseases. Multiple sclerosis, for example, stood out as having low rates of co-occurrence with other autoimmune diseases, suggesting a distinct pathophysiology.”

These findings reveal novel patterns that will inform the design of further research into the possible common causes of different autoimmune diseases.

Professor Geraldine Cambridge at UCL Medicine said: “Our study highlights the considerable burden that autoimmune diseases place upon individuals and the wider population. Disentangling the commonalities and differences within this large and varied set of conditions is a complex task. There is a crucial need, therefore, to increase research efforts aimed at understanding the underlying causes of these conditions, which will support the development of targeted interventions to reduce the contribution of environmental and social risk factors.”

Source: University College London

Categories : COVID Diseases, Syndromes and ConditionsTags :

Prior COVID Infection Linked to New Autoimmune Conditions

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In a new entry to the growing list of lasting complications from COVID infection, a large German cohort study of over 600 000 COVID patients indicates that new autoimmune conditions may result from previous COVID infection. The findings, which are awaiting peer review on the MedRxiv preprint server, show that the odds of new autoimmune conditions appear to increase in line with the severity of COVID infection.

After the acute phase of infection, some people may develop long-lasting symptoms, known as post-COVID, which are consistent with COVID infection and last more than 12 weeks. Most studies to date have focused on symptoms that partly wane over time. Many studies examined a small selective sample of patients, and only a few studies included a control group or information on chronic health conditions, such as SARS-CoV-2 infection.

Compared to post-COVID emergence of cardiovascular and other diseases, autoimmune diseases are less discussed in the literature, although autoantibodies could be found in patients after SARS-CoV-2 infection. So far there is limited evidence on newly manifested autoimmune diseases after an infection based on several case reports and one recent cohort study using UK health record data. In addition, COVID itself has some similarities with systemic autoimmune rheumatic diseases, which could make diagnosis difficult.

The researchers selected a cohort from German routine health care data, identifying individuals with polymerase chain reaction (PCR)-confirmed COVID through December 31, 2020. Patients were matched 1:3 to control patients without COVID. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyse the onset of autoimmune diseases during the post-acute period. The researchers calculated the incidence rates (IR) per 1000 person-years for each outcome and patient group, and estimated incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding COVID.

In total, 641 704 patients with COVID were included. When comparing the incidence rates in the COVID and matched control groups, the researchers found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID were at a greater risk for incident autoimmune diseases. These risk increases were as follows:

  • 41% higher risk of Grave’s disease
  • 42–45% higher risk of rheumatoid arthritis
  • 25% higher risk of type 1 diabetes
  • 27-29% higher risk of Crohn’s disease

The researchers concluded that SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection.

Categories : Mental Health Metabolic DisordersTags :

Genes and Environment Bridge Depression and Endocrine-metabolic Disorders

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While endocrine-metabolic disorders and depression are known to co-occur, genetic and environmental factors are known to underlie both. In a study examining the link, published in the American Journal of Psychiatry, analysis revealed the balance of genetic and environmental influences underlying the co-occurrence of depression for a range of endocrine-metabolic disorders.

It is known that there is elevated co-occurrence between endocrine-metabolic disorders and depression, but the relationship between them is still not well understood.

Familial aggregation

The authors identified 2.2 million individuals born in Sweden between 1973 and 1996, as well as their full and half siblings, and followed them up to age 40. A number of medical conditions were studied; depression and various endocrine-metabolic disorders, including three autoimmune diseases (autoimmune hypothyroidism, Graves’ disease, and type 1 diabetes) and three non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome).

Individuals with endocrine-metabolic disorders had 1.4 to 3.5 times the risk of depression compared to people without these diagnoses. Full and half siblings of these individuals also showed some elevated risk for depression, suggesting that genetic and/or environmental risk factors shared between family members play a role in the co-occurrence of these mental and physical disorders.

Genetic and environmental contributions

By comparing pairs of full sibling (who share about half of their genes) to pairs of half siblings (who share about a quarter of their genes), it was possible to calculate the relative contribution of genetic and environmental factors to the co-occurrence of depression and various endocrine-metabolic disorders. 

The results were a mix of these possibilities; the overlap between depression and non-autoimmune conditions was mainly explained by shared genetic influences, while environmental factors were predominantly involved in the association between depression and autoimmune disorders, particularly type 1 diabetes.

This indicates that the link between depression and different endocrine-metabolic disorders may be driven by different mechanisms. For example, shared biological mechanisms, such as immuno-inflammatory and metabolic dysregulations, may underlie the co-occurrence of depression and type 2 diabetes, obesity, and polycystic ovarian syndrome. In contrast, the absence of shared genetics in the association between type 1 diabetes and depression may reflect the existence of environmental factors influencing the risk of both conditions and/or a direct link between these conditions through mediating factors – eg, biological and psychosocial mechanisms connected to type 1 diabetes, including inflammation, cerebral damage, as well as stress of this lifelong condition that is often diagnosed early in life and that requires a complex management regime for both patients and their families.

“Our results underscore that clinicians should be aware of increased risks of depression in individuals with endocrine-metabolic disorders, and vice versa, and be vigilant for shared symptoms. This study also provides a useful foundation for future research aimed at identifying and targeting the biological mechanisms and modifiable risk factors underlying the co-presentation of endocrine-metabolic disorders and depression”, said Marica Leone, first author for the study.

Source: Karolinska Institutet

Categories : Cardiovascular Disease Diseases, Syndromes and ConditionsTags :

Array of Autoimmune Disorders Linked to Cardiovascular Disease

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A new epidemiological study published in The Lancet shows that patients with autoimmune disease have a substantially higher risk (between 1.4 and 3.6 times depending on which autoimmune condition) of developing cardiovascular disease (CVD) than people without an autoimmune disorder. This excess risk is comparable to that of type 2 diabetes, a well-known risk factor for cardiovascular disease.

Although earlier research has suggested associations between various different autoimmune disorders and a higher risk of cardiovascular disease, these studies were often too small and limited to selected autoimmune or selected cardiovascular conditions to draw conclusive evidence on the necessity of CVD prevention among patients with autoimmune disease.

At the annual congress of the European Society of Cardiology, researchers presented the outcome of a thorough epidemiological investigation into possible links between 19 of the most common autoimmune disorders and CVD. The research shows for the first time that cardiovascular risks affect autoimmune disease as a group of disorders, rather than selected disorders individually.

The whole cardiovascular disease spectrum

In the study, the authors show that the group of 19 autoimmune disorders they have studied accounts for about 6% of cardiovascular events. Importantly, excess cardiovascular risk was visible across the whole cardiovascular disease spectrum, beyond classical coronary heart disease, including infection-related heart disorders, heart inflammation, as well as thromboembolic and degenerative heart disorders, suggesting the implications of autoimmunity on cardiovascular health are likely to be much broader than originally thought. Furthermore, the excess risk was not explained by traditional cardiovascular risk factors such as age, sex or smoking. Another noteworthy finding: the excess risk is particularly high among patients with autoimmune disorders under 55 years and suggests that autoimmune disease is particularly important in causing premature cardiovascular disease, with the potential to result in a disproportionate loss of life years and disability.

The study was based on UK electronic health with data from about one-fifth of the current UK population. The researchers assembled a cohort of patients newly diagnosed with any of the nineteen autoimmune disorders. They then looked at the incidence of twelve cardiovascular outcomes – an unprecedented granularity that was made possible by the very large size of the dataset – in the following years, and they compared it to a matched control group. The risk of developing CVD for patients with one or more autoimmune disorders was on average 1.56 times higher than in those without autoimmune disease. The excess risk also rose with the number of different autoimmune disorders in individual patients. Among the disorders with the highest excess risk were systemic sclerosis, Addison’s disease, lupus and type I diabetes.

Need for targeted prevention measures

The results show that action is needed, said Nathalie Conrad, lead author of the study. “We see that the excess risk is comparable to that of type 2 diabetes. But although we have specific measures targeted at diabetes patients to lower their risk of developing cardiovascular disease (in terms of prevention and follow-up), we don’t have any similar measures for patients with autoimmune disorders.” Conrad also noted that the European Society of Cardiology guidelines on the prevention of cardiovascular diseases, do not yet mention autoimmunity as a cardiovascular risk factor, only mentioning specific disorders such as lupus, nor do they list any specific prevention measures for patients with autoimmune disease.

Conrad hopes the study will raise awareness among patients with autoimmune disease and clinicians involved in the care of these patients, which will include many different specialties such as cardiologists, rheumatologists, or general practitioners. ‘We need to develop targeted prevention measures for these patients. And we need to do further research that helps us understand why patients with an autoimmune disorder develop more cardiovascular diseases than others, and how we can prevent this from happening.’

The underlying mechanisms are still poorly understood. Conrad said: “The general hypothesis is that chronic and systemic inflammation, which is a common denominator in autoimmune disorders, can trigger all sorts of cardiovascular disease. Effects of autoimmune disease on connective tissues, small vessels, and cardiomyocytes, and possibly some of the treatments commonly used to treat autoimmunity are also likely to contribute to patients’ cardiovascular risk. This really needs to be investigated thoroughly.”

Source: KU Leuven

Categories : Diseases, Syndromes and ConditionsTags :

Gene Mutation in Young Girl May Finally Yield Lupus Treatment

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Facial rash characteristic of lupus. Credit: Statpearls

A study published in Nature has identified mutations in an X chromosome gene that senses viral RNA, as a cause of the autoimmune disease lupus, a finding which may explain why the disease is far more common in females, and which might lead to new treatments.

In the study, whole genome sequencing was performed on the DNA of a Spanish child named Gabriela, who was diagnosed with severe lupus at age 7. Such a severe case with early onset of symptoms is rare and suggests a single genetic cause.

In their genetic analysis, the researchers discovered a single point mutation in the TLR7 gene. Referrals from other institutions, they were able to identify other cases of severe lupus where this gene was also mutated.

To confirm that the mutation causes lupus, the team inserted the gene into mice, which went on to develop the disease and showed similar symptoms. The mouse model and the mutation were both named ‘kika’ by Gabriela, the young girl central to this discovery.

Carola Vinuesa, senior author and principal investigator said: “It has been a huge challenge to find effective treatments for lupus, and the immune-suppressors currently being used can have serious side effects and leave patients more susceptible to infection. There has only been a single new treatment approved by the FDA in about the last 60 years.

“This is the first time a TLR7 mutation has been shown to cause lupus, providing clear evidence of one way this disease can arise.”

Professor Nan Shen, co-director of CACPI adds: “While it may only be a small number of people with lupus who have variants in TLR7 itself, we do know that many patients have signs of overactivity in the TLR7 pathway. By confirming a causal link between the gene mutation and the disease, we can start to search for more effective treatments.”

The mutation identified by the researchers makes TLR7 protein bind more readily guanosine and become more active. This in turn increases the sensitivity of the immune cell, making it more likely to incorrectly target healthy tissue.

Interestingly, other studies have shown mutations that cause TLR7 to become less active are associated with some cases of severe COVID infection, highlighting the delicate balance of a healthy immune system.

The findings could also explain why lupus is 10 times more common in females than in males. Because TLR7 is located on the X chromosome, females have two copies of the gene while males have one. Usually, in females one of the X chromosomes is inactive, but in this section of the chromosome, silencing of the second copy is often incomplete. This means females with a mutation in this gene can have two functioning copies.

Study co-author Dr Carmen de Lucas Collantes, said: “Identification of TLR7 as the cause of lupus in this unusually severe case ended a diagnostic odyssey and brings hope for more targeted therapies for Gabriela and other lupus patients likely to benefit from this discovery.”

Gabriela, now a teenager, remains in touch with the research team. She said, “I hope this finding will give hope to people with lupus and make them feel they are not alone in fighting this battle. Hopefully the research can continue and end up in a specific treatment that can benefit so many lupus warriors who suffer from this disease.”

The researchers are now investigating the repurposing of existing treatments which target the TLR7 gene. By targeting this gene, they hope to be able to also help patients with related conditions.

Carola added: “There are other systemic autoimmune diseases, like rheumatoid arthritis and dermatomyositis, which fit within the same broad family as lupus. TLR7 may also play a role in these conditions.”

Source: Francis Crick Institute

Categories : Diseases, Syndromes and ConditionsTags :

Vitamin D Supplements Reduce Autoimmune Disease Risk

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A five year-long randomised, placebo-controlled study found that in older adults taking vitamin D supplements, alone or with omega-3 fatty acids, the risk of developing autoimmune disease was reduced.

Autoimmune diseases (AD) such as rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease and psoriasis, are a leading cause of morbidity and mortality as people age. Few effective treatments are available for AD, but some research has hinted that supplements, including vitamin D and omega-3 fatty acids, could have beneficial effects.

In a new study published in the BMJ, investigators from Brigham and Women’s Hospital evaluated whether taking vitamin D and/or omega fatty acid supplements could affect rates of AD. The large-scale vitamin D and Omega-3 Trial (VITAL), a randomised study which followed participants for approximately five years. Taking vitamin D, or vitamin D and omega-3 fatty acids had a significantly lower rate of AD than placebo.

“It is exciting to have these new and positive results for non-toxic vitamins and supplements preventing potentially highly morbid diseases,” said senior author Karen Costenbader, MD, MPH. “This is the first direct evidence we have that daily supplementation may reduce AD incidence, and what looks like a more pronounced effect after two years of supplementation for vitamin D.”

“Now, when my patients, colleagues, or friends ask me which vitamins or supplements I’d recommend they take to reduce risk of autoimmune disease, I have new evidence-based recommendations for women aged 55 years and older and men 50 years and older,” said Dr Costenbader. “I suggest vitamin D 2000 IU a day and marine omega-3 fatty acids (fish oil), 1000 mg a day – the doses used in VITAL.”

VITAL included 25 871 participants, with men aged 50 and older and women aged 55 and older, conducted to investigate whether taking vitamin D3 and/or omega-3 supplements could reduce the risk for developing cancer, heart disease and stroke in people who do not have a prior history of these illnesses. Prior to the launch of VITAL, investigators determined that they would also look at rates of AD among participants, as part of an ancillary study.

Participants answered questionnaires about new diagnoses of diseases, including rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis and inflammatory bowel disease, with space to write in all other new onset ADs. Medical records were reviewed to confirm reported diagnoses.

“Autoimmune diseases are common in older adults and negatively affect health and life expectancy. Until now, we have had no proven way of preventing them, and now, for the first time, we do,” said first author Jill Hahn, ScD, post-doctoral fellow at the Brigham.

Among patients randomised to vitamin D, 123 participants in the treatment group and 155 in the placebo group were diagnosed with confirmed AD (22 percent reduction). Among those in the fatty acid arm, confirmed AD occurred in 130 participants in the treatment group and 148 in the placebo group. Omega-3 fatty acids alone did not significantly lower incidence of AD, but there was some evidence of a decrease over long periods.

Source: EurekAlert!

Categories : Diseases, Syndromes and ConditionsTags :

New AIRD Therapies Could Cut Side-effects

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Source: Pixabay

New therapies for autoimmune rheumatic diseases (AIRDs) that are designed to better regulate lipid metabolism could significantly reduce the harmful side-effects caused by conventional treatments, researchers found in a new large-scale review.

AIRDs include rheumatoid arthritis, lupus and Sjögren’s syndrome – conditions which affect millions and all with high rates of morbidity. The pathogenesis of autoimmune conditions is still ill-defined and delivering targeted therapeutic strategies is challenging.

As a result, current treatments for AIRDs are primarily designed to suppress the symptoms (inflammation), but are ‘low target’, ie may also have unintended side-effects. In this regard, AIRDs drugs often cause changes to cell metabolism (such as lipid metabolism) and function, putting patients at greater risk of co-morbidities such as cardiovascular disease (CVD).

Lead author Dr George Robinson (Centre for Rheumatology Research, UCL Division of Medicine) said: “While the mechanisms that cause rheumatic diseases are ill-defined, some recent research indicates cell metabolism may play an important role in triggering or worsening their onset or affect.

“In this review we therefore sought to understand the effect of both conventional and emerging therapies on lipid metabolism in patients with AIRDs.”

For the study, published in the Journal of Clinical Investigation, researchers reviewed more than 200 studies to assess and interpret what is known regarding the on-target/off-target adverse effects and mechanisms of action of current AIRD therapies on lipid metabolism, immune cell function and CVD risk.

Explaining the findings, Dr Robinson said: “Our review found that current AIRD therapies can both improve or worsen lipid metabolism, and either of these changes could cause inflammation and increased CVD risk.

“Many conventional drugs also require cell metabolism for their conversion into therapeutically beneficial products; however drug metabolism often involves the additional formation of toxic by-products, and rates of drug metabolism can be different between patients.”

The review noted that optimal combinations of immunosuppressive treatments to better control inflammation could lead to an improved metabolic/lipid profile in AIRDs.

However, many studies also showed that lipid lowering drugs such as statins do not sufficiently lower CVD risk in some AIRDs, possibly because they cannot completely restore the anti-inflammatory properties

Dr Robinson added: “The unfavourable off-target adverse effects of current therapies used to treat AIRDs provides an opportunity for optimal combination co-therapies targeting lipid metabolism that could reduce immune complications and potential increased CVD risk in patients.

“New therapeutic technologies and research have also highlighted alternative metabolic pathways that can be more specifically targeted to reduce inflammation but also to prevent undesirable off-target metabolic consequences of conventional anti-inflammatory therapies.”

Source: University College London

Categories : Medical Research & TechnologyTags :

New Type of Skin Cell Reveals Secrets of Inflammation

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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

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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