Tag: rheumatoid arthritis

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 : Diseases, Syndromes and Conditions Environmental EffectsTags :

Strong Link Between Polycyclic Aromatic Hydrocarbons and Rheumatoid Arthritis Risk

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Exposure to polycyclic aromatic hydrocarbons (PAH), formed from burning various substances such as coal, wood or tobacco, or from grilled meat, is strongly linked to a person’s risk of developing rheumatoid arthritis, suggests research published in the open access journal BMJ Open.

These chemicals also seem to account for most of smoking’s impact on risk of the disease, the findings indicate. Growing evidence links several environmental toxicants with various long term conditions. But few studies have looked at their association with inflammatory conditions, such as rheumatoid arthritis, which is thought to arise from an interplay between genes, sex, and age, and environmental factors, including smoking, nutrition, and lifestyle.

To try and shed some light on the potential role of environmental exposure on rheumatoid arthritis risk, the researchers drew on responses to the nationally representative US National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016.

NHANES evaluates a wide variety of toxicants, including PAH; chemicals used in the manufacture of plastics and various consumer products (PHTHTEs); and volatile organic compounds (VOCs), derived from paints, cleaning agents, and pesticides, among other things; along with data related to health, nutrition, behaviours and the environment.

The study included 21 987 adults, 1418 of whom had rheumatoid arthritis and 20 569 of whom didn’t. Blood and urine samples were taken to measure the total amount of PAH (7090 participants), PHTHTEs (7024), and VOCs (7129) in the body.

The odds of rheumatoid arthritis were highest among those in the top 25% of bodily PAH levels, irrespective of whether or not they were former or current smokers.

After accounting for potentially influential factors, including dietary fibre intake, physical activity, smoking, household income, educational attainment, age, sex, and weight (BMI), only one PAH, 1-hydroxynaphthalene, was strongly associated with higher odds (80%) of the disease.

PHTHTE and VOC metabolites weren’t associated with heightened risk after accounting for potentially influential factors.

Somewhat surprisingly, however, smoking wasn’t associated with heightened rheumatoid arthritis risk either, after accounting for PAH levels in the body. 

And further analysis to separate out the influences of PAH and smoking showed that bodily PAH level accounted for 90% of the total effect of smoking on rheumatoid arthritis risk.

This is an observational study, and as such, can’t determine cause. And the researchers acknowledge various limitations to their findings, including that measurements of environmental toxicants in fat (adipose) tissue weren’t available.

Nor did they measure heavy metal levels which have previously been linked to rheumatoid arthritis risk. Cigarettes are a major source of the heavy metal cadmium.

But they write: “To our knowledge, this is the first study to demonstrate that PAH not only underlie the majority of the relationship between smoking and [rheumatoid arthritis], but also independently contribute to [it]. 

“This is important as PAH are ubiquitous in the environment, derived from various sources, and are mechanistically linked by the aryl hydrocarbon receptor to the underlying pathophysiology of [rheumatoid arthritis].”

They add: “While PAH levels tend to be higher in adults who smoke…other sources of PAH exposure include indoor environments, motor vehicle exhaust, natural gas, smoke from wood or coal burning fires, fumes from asphalt roads, and consuming grilled or charred foods.

“This is pertinent as households of lower socioeconomic status generally experience poorer indoor air quality and may reside in urban areas next to major roadways or in high traffic areas.” These people may therefore be particularly vulnerable, they suggest.

Source: The BMJ

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 : Environmental EffectsTags :

Occupational Dust and Fumes Exposure may Raise Rheumatoid Arthritis Risk

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Breathing in common workplace dust and fumes may increase the risk of developing severe rheumatoid arthritis, especially in combination with smoking and genetic susceptibility to the disease, suggests a new study published in The Annals of the Rheumatic Diseases.

Rheumatoid arthritis (RA) is a chronic autoimmune joint disorder affecting up to 1% of the population. The presence of so-called anti-citrullinated protein antibodies (ACPA) denotes a worse prognosis with higher rates of erosive joint damage.

Cigarette smoking is already known as a risk factor for developing RA, but the impact of breathing in workplace dust and fumes, such as vapours, gases, and solvents, remains unclear.

Increased risk of ACPA-positive rheumatoid arthritis

Researchers at Karolinska Institutet drew on data from the Swedish case-control study EIRA (Epidemiological Investigation of RA), comprising 4033 people diagnosed with RA between 1996 and 2017 and 6485 randomly selected healthy controls matched for age and sex. Personal job histories were used to estimate the exposure to 32 inhalable workplace agents. Each participant was assigned a genetic risk score based on their genetic susceptibility to developing RA.

Individuals who had been exposed to any of the occupational agents had a 25 per cent higher risk of developing ACPA-positive RA, and the risk increased with a longer duration of exposure or with more types of exposed agents. 17 out of 32 agents, including quartz, asbestos, diesel fumes, gasoline fumes, carbon monoxide, and fungicides, were strongly associated with an increased risk of developing ACPA-positive RA, but only a few agents were associated with ACPA-negative RA.

Interaction with smoking and risk genes

Individuals who were exposed to smoking as well as inhalable workplace agents, in combination with having a high genetic risk score, had an 18 times higher risk of developing ACPA-positive RA compared with those who were not exposed to any of these three factors.

“Occupational inhalable agents could act as important environmental triggers in RA development and interact with smoking and RA risk genes,” says Karolinska Institutet professor and corresponding author Lars Klareskog. “Preventive strategies aimed at reducing occupational hazards and smoking are warranted for reduction of the burden of RA, especially for those who are genetically vulnerable.”

Because it is an observational study, it cannot establish any causal relationships.

Source: Karolinska Institutet

Categories : AgeingTags :

Assessing the Effectiveness of Chinese Traditional Medicine for Rheumatoid Arthritis

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Chinese traditional medicine based on combinations of typically 5 to ten plants, usually boiled and administered as a decoction or tea, has long been used to treat rheumatoid arthritis (RA), but few clinical trials have tested its potential. A review in the Journal of Internal Medicine outlines a strategy to analyse the ability of different mixtures of plants used in Chinese medicine to combat RA.

One fundamental of traditional medicine is to prevent disease. RA is an autoimmune, inflammatory and chronic disease that primarily affects the joints of 0.5%–1% of the population. In two out of three of the cases, the patients are characterised by the presence of autoantibodies such as the rheumatoid factor and the more disease-specific autoantibody against citrullinated proteins, so-called ‘ACPA’ (anticitrullinated protein/peptide antibodies). ACPA positivity is also strongly associated with specific variations in the HLA-DRB1 gene, the shared epitope alleles. Together with smoking, these factors account for the major risks of developing RA. 

The researchers’ strategy involves isolating the active components of individual plants and testing them alone or in combinations against key pathways of disease pathology, followed by experiments conducted in animal models of RA.

“A substantial number of our current drugs are natural products or derivatives thereof, and without doubt nature will continue to be a source of future discoveries,” the authors wrote. “Therefore continuous research based on the traditional use of plants is highly motivated. In our opinion, the strategy of starting from knowledge in traditional medicine, followed by the combination of in vivo evidence of efficacy and bioassay-guided isolation to understand the chemistry and pathways involved, is one effective way forward.”

Source: Wiley

Categories : AgeingTags : 1 Comment

Treatment of Rheumatoid Arthritis Before Disease Develops Yields Benefits

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A temporary treatment with methotrexate in the early stages of rheumatoid arthritis resulted in benefits for patients, according to research published in The Lancet. By temporarily prescribing methotrexate in the “pre-rheumatic phase,” patients experienced a reduction long-term joint inflammations, pain and physical limitations.

“At present, methotrexate is only prescribed to the patient following a rheumatoid arthritis diagnosis,” explained Annette van der Helm, Professor of Rheumatology at Leiden University Medical Centre. “But that is too late. By then, the disease is already considered chronic.” The researchers hope to prevent or reduce disease burden by giving methotrexate to patients likely to develop rheumatoid arthritis.

The researchers found that while the development of rheumatoid arthritis was not prevented by early treatment, diagnosis was delayed. Patients that had temporarily received methotrexate also reported less pain, morning stiffness and daily functioning impediments. Fewer joint inflammations were seen in MRI scans. “This is an important step towards reducing disease burden for this group of patients,” said Prof Van der Helm. “Moreover, it serves as initial evidence for initiating treatment in the ‘pre-rheumatic’ phase.”

The 8 year study included more than 230 patients. “All suffered from joint pain and inflammation, which could be seen on the MRI, and was thought to be a rheumatism precursor,” said PhD student Doortje Krijbolder. Rheumatologists are not certain whether this is truly the case, however. Pre-rheumatoid patients were treated with methotrexate or a placebo for one year, and a one year follow-up enabled researchers to see if the effects of the treatment persisted.

“This chronic disease is extremely burdensome to patients and their families. Our study is paving the way toward arthritis prevention,” said Prof Van der Helm. “To achieve this completely, greater understanding of the molecular processes underlying the chronic nature of rheumatoid arthritis is necessary.”

Source: Medical Xpress

Categories : Diseases, Syndromes and ConditionsTags :

New AIRD Therapies Could Cut Side-effects

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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 : AgeingTags :

Why Does Arthritis Flare Up in the Same Place?

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A new study has revealed why arthritis has a tendency to flare up in the same location instead of around the body.

When joints flare up in people with rheumatoid arthritis and related diseases, the joints involved are often the same as those previously affected. For example, if arthritis started in the right knee, it is much more likely to flare there than in the left knee, even if the arthritis had been in remission for years. Because of this, each patient develops a highly individual disease pattern, though why this is so has remained unclear.

“Overwhelmingly, flares occur in a previously involved joint,” said Peter Nigrovic, MD, chief of the division of immunology at Boston Children’s Hospital. “Something in that joint seems to remember, ‘this is the joint that flared before.’”

A new study, co-led by Dr Nigrovic and published in Cell Reports, shows where that memory is housed: in a type of immune cell called a tissue-resident memory T cell. Specifically, these T cells reside in the synovium, the tissue that lines the inside of the capsule surrounding the joint.
“We showed that these T cells anchor themselves in the joints and stick around indefinitely after the flare is over, waiting for another trigger,” said Dr Nigrovic. “If you delete these cells, arthritis flares stop.”

The team demonstrated this phenomenon in three separate mouse models of inflammatory arthritis. Two models used chemical triggers to cause joint inflammation, and the third had a protein knocked out that blocks the pro-inflammatory cytokine IL-1. Once activated, resident memory T cells in the joints rallied other immune cells, leading to an arthritis flares limited to specific joints. Elimination of these T cells prevented further flares from occurring.

“Right now, treatment of rheumatoid arthritis has to continue lifelong; although we can successfully suppress disease activity in many patients, there is no cure,” said Dr Nigrovic. “We think our findings may open up new therapeutic avenues.”

Dr Nigrovic also believes the findings apply to other types of autoimmune arthritis, including juvenile idiopathic arthritis.

Dermatology provided a cue for the researchers: tissue-resident memory T cells were originally found in skin, where a ‘memory’ pattern is well known to dermatologists. In psoriasis, for example, patients get recurrent plaques in the same places. The same often holds true in cutaneous hypersensitivity reactions, such as reactions to nickel in jewelry or wristwatches. “A person reacting to nickel through a belt buckle may also develop a rash on their wrist, where they wore a nickel-containing watch as a child,” observed Dr Nigrovic.

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

New Approach to Address Cardiac Disease in Rheumatoid Arthritis

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A new approach to address cardiac disease in rheumatoid arthritis (RA) patients has been developed.

Currently patients suffering from RA are also particularly susceptible to diastolic dysfunction, a type of cardiac deficiency which may lead to heart failure, resulting in a higher mortality rate among such patients.
To address this unmet clinical need, researchers from Queen Mary’s William Harvey Research Institute (WHRI) responded by developing an experimental model of cardiomyopathy in inflammatory arthritis.

After several attempts, the researchers finally hit upon the right model by characterising experimental animals with arthritis. The animals developed cardiac diastolic dysfunction, recapitulating the symptoms presented by RA patients. Diastolic dysfunction means the heart is able to contract as normal but unable to dilate properly, ultimately leading to heart failure over time.

Professor Mauro Perretti, lead study author and Professor of Immunopharmacology at Queen Mary University of London said, “As is often the case, the description of a valid model of disease can open new vistas on pathogenic mechanisms as well as on novel therapeutic approaches. At present, the cardiomyopathy of patients affected by rheumatoid arthritis is not treated, and on top of this, current anti-rheumatic drugs (eg biologics or steroids) may even worsen it. As such there is an urgent therapeutic need to intervene and treat, if not cure, the cardiomyopathy of patients affected by rheumatoid arthritis.”

“The broad area of cardiac inflammation is largely unexplored. At the WHRI we have several groups addressing experimental and translational work on several syndromes of the heart. Thus, there is work on myocarditis, on diabetes-induced cardiomyopathy and now with this study, the cardiomyopathy of inflammatory arthritis. The WHRI at Queen Mary University of London is a place of excellence to study cardiac inflammation in all its multiple faces, thanks also to our partnership with the Barts Heart Centre at Barts Health NHS Trust.”

The study was published in PNAS.

Source: EurekAlert!

Categories : AgeingTags :

Parental Smoking Linked to Children’s Later Arthritis

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In a new study, parental smoking was linked to an elevated risk of children developing rheumatoid arthritis when they reach adulthood.

Drawing on data for 90 923 participants in the Nurses’ Health Study II (which included female registered nurses aged 25–42 years in 1989), the researchers found that 532 developed rheumatoid arthritis during a median follow-up of 27.7 years. Parental smoking when the participants were children was associated with a 75% higher risk of developing rheumatoid arthritis, even after controlling for personal smoking when the participants were adults. Among participants who went on to smoke as adults, this risk was even greater.

“These results suggest that early life inhalant exposures such as passive smoking may predispose individuals to develop rheumatoid arthritis later in life,” said senior author Jeffrey A. Sparks, MD, MMSc, of Brigham and Women’s Hospital.

“We used advanced statistical methods that allowed us to decipher the potential direct harm of early-life passive smoking experience on rheumatoid arthritis risk, while also taking into account factors occurring throughout adulthood,” added lead author Kazuki Yoshida, MD, ScD.

The study findings were published in Arthritis & Rheumatology.

Source: Wiley