Tag: rheumatoid arthritis

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

Categories : AgeingTags :

Bacteria in the Mouth Linked to Arthritis

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Researchers found similar oral bacterial compositions among patients with early rheumatoid arthritis and those at risk of developing the disease, compared with healthy individuals who were not at risk.

The oral cavity is host to approximately 800 identified species of bacteria. The periodontum, ie the tissue surrounding the tooth, can become inflamed because of a complex interaction of bacterial infection and the body’s response, modified by behavioural factors such as smoking, result in periodontal disease. Periodontal disease has been shown to be caused by certain diseases and medical conditions, and may also cause them. Periodontitis is prevalent among rheumatoid arthritis patients. 

The researchers recruited three groups of 50 participants each: early rheumatoid arthritis patients, at‐risk individuals, and healthy controls. They were given periodontal examinations and assessed for bleeding on probing, pocket probing depth, and periodontal inflamed surface area. The microbial composition of subgingival dental plaque, saliva, and tongue coating was assessed using 16S rDNA amplicon sequencing, and compared between groups.

They found that patients and at-risk individuals had an increased relative abundance of potentially pro- inflammatory bacteria in the mouth, suggestive of a possible relationship between oral microbes and rheumatoid arthritis.

“Prevotella and Veillonella–both gram-negative anaerobes–were at higher relative abundance in saliva, and Veillonella was also at higher relative abundance in tongue coating, of both early rheumatoid arthritis patients and at-risk individuals compared to healthy controls,” the authors wrote.

The findings were published in Arthritis & Rheumatology.  

Source: News-Medical.Net

Journal information: Kroese, J. M., et al. (2021) The oral microbiome in early rheumatoid arthritis patients and individuals at risk differs from healthy controls. Arthritis & Rheumatology. doi.org/10.1002/art.41780.