autoimmune conditions

Posted on autoimmune conditions, Rheumatoid arthritis

Long term exposure to air pollution linked to heightened autoimmune disease risk

Polluted Air is a Possible Cause of Dementia

Long term exposure to air pollution is linked to a heightened risk of autoimmune disease, particularly rheumatoid arthritis, connective tissue and inflammatory bowel diseases, finds research published online in the open access journal RMD Open.

Environmental air pollution from vehicle exhaust and industrial output can trigger adaptive immunity–whereby the body reacts to a specific disease-causing entity. But sometimes this adaptive response misfires, prompting systemic inflammation, tissue damage, and ultimately autoimmune disease. 

Examples of autoimmune disease include rheumatoid arthritis; systemic lupus erythematosus; inflammatory bowel diseases, such as ulcerative colitis; connective tissue disease, such as osteoarthritis; and multiple sclerosis.

Both the incidence and prevalence of these conditions have steadily increased over the past decade, the reasons for which aren’t entirely clear. And whether air pollution is linked to a heightened risk of autoimmune disease remains a matter of debate, say the researchers.

To try and shed some light on the issues, the researchers mined the national Italian fracture risk database (DeFRA) and retrieved comprehensive medical information on 81,363 men and women submitted by more than 3500 doctors between June 2016 and November 2020.

Most were women (92%) with an average age of 65, and 17866 (22%) had at least one co-existing health condition. 

Each participant was linked to the nearest air quality monitoring station run by the Italian Institute of Environment Protection and Research via their residential postcode. 

The researchers were particularly interested in the potential impact of particulate matter (PM10 and PM2.5). Levels of 30µg/m3 for PM10 and 20µg/m3 for PM2.5 are the thresholds generally considered harmful to human health.

Some 9723 people (12%) were diagnosed with an autoimmune disease between 2016 and 2020.

Information on air quality was obtained from 617 monitoring stations in 110 Italian provinces. Average long term exposure between 2013 and 2019 was 16 µg/m3 for PM2.5 and 25 µg/m3 for PM10.

Exposure to PM2.5  wasn’t associated with a heightened risk of an autoimmune disease diagnosis. But PM10 was associated with a 7% heightened risk for every 10µg/m3 increase in levels, after accounting for potentially influential factors.

Long term exposure to PM10 above 30 µg/m3 and to PM2.5 above 20 µg/m3 were associated with, respectively, a 12% and 13% higher risk of autoimmune disease. 

And long term exposure to PM10 was specifically associated with a heightened risk of rheumatoid arthritis, while long term exposure to PM2.5 was associated with a heightened risk of rheumatoid arthritis, connective tissue diseases, and inflammatory bowel diseases.

Overall, long term exposure to traffic and industrial air pollutants was associated with an approximately 40% higher risk of rheumatoid arthritis, a 20% higher risk of inflammatory bowel disease, and a 15% higher risk of connective tissue diseases.

This is an observational study, and as such, can’t establish cause. And the researchers acknowledge several limitations which might have affected their findings.

These include: the lack of information on the dates of diagnosis and start of autoimmune disease symptoms; that air quality monitoring might not reflect personal exposure to pollutants; and that the findings might not be more widely applicable because study participants largely comprised older women at risk of fracture. 

But air pollution has already been linked to immune system abnormalities, and smoking, which shares some toxins with fossil fuel emissions, is a predisposing factor for rheumatoid arthritis, they explain.

Posted on autoimmune conditions

Fight friendly fire with fire: an antibody for treating autoimmune disease

Fig.


Anti-RGMa antibody treatment ameliorates NMO pathophysiology CREDITTakahide Itokazu

Autoimmune diseases are the molecular equivalent of “friendly fire”: the body attacks itself instead of harmful invaders. Now, researchers from Japan have found that interrupting the complex interplay between different immune cell types can help prevent the damage that this friendly fire causes in one type of autoimmune disease.

In a study published in this month in Annals of Neurology, researchers from Osaka University have revealed that treatment with an antibody to a protein called repulsive guidance molecule-a (RGMa) dramatically improves symptoms of neuromyelitis optica, a devastating autoimmune disorder, in an experimental rat model.

Neuromyelitis optica (NMO) is an inflammatory disorder that can cause pain, paralysis, and even death. In most cases, NMO is caused by antibodies that the body develops to a protein called aquaporin-4 (AQP4). These anti-AQP4 antibodies leak into the tissue at sites of nerve damage that also show massive accumulation of neutrophils. This neutrophil build-up is associated with the death of cells called astrocytes, which ultimately causes NMO symptoms.

“We recently found that injecting rats with an antibody to RGMa can decrease the severity of NMO symptoms,” says lead author of the study Shosuke Iwamoto. “However, it was still unclear how this treatment works mechanistically, whether by affecting AQP4, astrocytes, or some other factor.”

To address this, the researchers used a clinically relevant rat model of NMO  to test the effects of the anti-RGMa antibody on disease symptoms, as well as gene and protein expression.

“Our findings revealed a new molecular mechanism of NMO pathophysiology in which RGMa stimulates macrophages to attract neutrophils to the lesions, where they kill off astrocytes,” explains Toshihide Yamashita, senior author.

Importantly, treating rats with an antibody to RGMa prevented these effects, resulting in fewer neutrophils around nerve lesions, less astrocyte killing, and a decrease in symptoms like movement problems and pain.

“Our findings suggest that anti-RGMa antibodies may represent an effective therapeutic strategy for NMO-associated neuropathic pain and motor deficits in patients with NMO,” says Iwamoto.

Given that the severity of acute NMO attacks greatly affects patients’ long-term outcomes, treatments targeting RGMa that help reduce the severity of the attack or enhance the recovery process are crucial for improving their quality of life. Treatment with an anti-RGMa antibody could potentially even be helpful in preventing NMO relapses in the chronic stage of the disease.

Posted on autoimmune conditions

How to deal with autoimmune disease flare!

How to deal with autoimmune disease flares- A Rheumatologist POV - YouTube


Flares happen. We do everything we can to prevent them and to understand why they occur. But sometimes they just happen. This is true regardless of the inflammatory or autoimmune disease: lupus, arthritis, fibromyalgia, vasculitis and all the others. As frustrating as they can be, there are things you can do to manoeuvre your way through them with care and grace.


Posted on autoimmune conditions

Autoimmune diseases: discovery of central building block in immune cells

Sunshine may shield children, young adults from MS

Autoimmune diseases are triggered when the immune system malfunctions and attacks the body’s own structures. Although there is not, as yet, any cure for such diseases, their progression can be slowed down by therapeutic measures. Researchers at MedUni Vienna’s Center for Physiology and Pharmacology have now discovered a central signaling pathway in immune cells that may help in the development of a new therapeutic approach. Their study was recently published in the journal Cell Reports.

The immune system protects the body from infections of all kinds and is designed to distinguish between foreign threats and the body’s own tissues. T cells, which are deployed at the command of other immune cells, the dendritic cells, are an important component of the immune system. The dendritic cells are not only responsible for activating the T cells but also for deactivating them – primarily to prevent them from attacking the body’s own tissues. This mechanism, known as immunotolerance, is the key to the current treatments for autoimmune diseases, whereby certain pharmaceutical agents (JAK inhibitors) are used. The aim is to inhibit T-cell activity against endogenous structures, so as to slow down the progression of the autoimmune disease.

JAK inhibitors are used to treat various autoimmune diseases, such as rheumatoid arthritis. The effect of the inhibitors – on all immune cells simultaneously – has been demonstrated in several studies. A research team led by Gernot Schabbauer and Omar Sharif from the Institute of Vascular Biology and Thrombosis Research at MedUni Vienna’s Center for Physiology and Pharmacology has now investigated the specific effect of JAK inhibitors on dendritic cells and, in particular, the role played by the immunotolerance of T cells (peripheral T cell tolerogenesis) in autoimmune diseases.

Targeted cell-based therapy
Working in collaboration with scientists at the Christian Doppler Laboratory for Arginine Metabolism in Rheumatoid Arthritis and Multiple Sclerosis at MedUni Vienna and St. Anna Children’s Cancer Research, they discovered a key building block in immune cells that is relevant in the context of autoimmune diseases. “This is the signaling pathway in dendritic cells that promotes T-cell tolerogenesis. This enables the dendritic cells to increase the immunotolerance of the T cells in particular and prevent them from attacking the body’s own structures,” explains the study’s lead author Andrea Vogel from MedUni Vienna’s Institute of Vascular Biology and Thrombosis Research.

The researchers’ findings are a step towards a potential new cell-based therapeutic approach for autoimmune diseases. The aim is to specifically target the signaling pathway in the dendritic cells, so as to “switch off” the misdirected T cells and slow down progression of the autoimmune disease. Further research on this will follow, emphasises Andrea Vogel: “The next thing we want to investigate is whether this signaling pathway in dendritic cells also plays a role in cancer.”

Posted on autoimmune conditions, Diet

Towards a treatment for gluten intolerance

Free from Gluten
Free from Gluten


Celiac disease is a severe autoimmune disorder of the intestine. It occurs when people develop sensitivity to gluten, a substance found in wheat, rye, and barley. An international research team from Italy and France has now uncovered a new molecular player in the development of gluten intolerance. Their discovery, published in The EMBO Journal, suggests potential targets for the development of therapeutic approaches for the disease.

Celiac disease can appear in people who are genetically predisposed, but it is triggered through environmental factors. When people suffering from celiac disease eat gluten, their immune system triggers a response against their body’s own cells, damaging the mucosal surface of the small intestine. About 1 in 100 people suffer from celiac disease, but the prevalence is about three times higher in patients who also suffer from cystic fibrosis. “This co-occurrence made us wonder if there is a connection between the two diseases at the molecular level,” said Luigi Maiuri of the University of Piemonte Orientale in Novara and San Raffaele Scientific Institute in Milan, Italy, who led the research together with Valeria Raia (University Federico II of Naples, Italy) and Guido Kroemer (University of Paris Descartes, France).

Cystic fibrosis is characterized by the build-up of thick and sticky mucus in the patients’ lungs and intestine. It is caused by mutations of the gene coding for cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is an ion transport protein that plays an important role in keeping mucus fluid – when it fails, the mucus clogs up. Moreover, CFTR malfunction triggers a number of additional reactions in the lungs and other organs including intestine by activation of the immune system. These effects are very similar to the responses triggered by gluten in celiac patients. Maiuri, Kroemer and their colleagues took a closer look at the molecular underpinnings of these similarities.

Gluten is difficult to digest, so that relatively long protein parts – peptides – enter the intestine. Using human intestinal cell lines that are sensitive to gluten, the researchers found that one specific peptide, P31-43, directly binds to CFTR and impairs its function. This interaction triggers cellular stress and inflammation, suggesting that CFTR plays a central role in mediating gluten sensitivity in celiac patients.

Moreover, the interaction between P31-43 and CFTR can be inhibited by a potentiator of CFTR, called VX-770. When intestinal cells or tissue samples collected from celiac disease patients were pre-incubated with VX-770 before being exposed to P31-43, the peptide did not elicit an immune reaction. Thus, VX-770 protects gluten-sensitive epithelial cells from the detrimental effect of gluten. In addition, the researchers found that VX-770 could protect gluten-sensitive mice from gluten-induced intestinal symptoms.

There is, as yet, no cure for celiac disease; the only therapeutic strategy is to keep a strict diet. However, the current study is a promising step towards the development of a treatment. It suggests that CFTR potentiators, which have been developed to treat cystic fibrosis, may also be explored as a starting point for the development of a remedy for celiac disease.