Tag: rheumatoid arthritis

Categories : Ageing RheumatologyTags : Leave a comment

Immune Ageing Found to Drive – Not Be Driven by – Rheumatoid Arthritis

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Rheumatoid arthritis. Credit: Scientific Animations CC4.0

Features of immune system ageing can be detected in the earliest stages of rheumatoid arthritis (RA), even before clinical diagnosis, a new study has found which provides at-risk individuals with hope for early intervention.

The research led by academics at the University of Birmingham, delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, and published in the journal eBioMedicine shows that individuals with joint pain or undifferentiated arthritis already exhibit signs of a prematurely aged immune system, suggesting that immune ageing may play a direct role in the development of RA.

The study involved 224 participants across various stages of RA development and was funded by FOREUM and the European League Against Rheumatism (EULAR). It represents one of the most comprehensive analyses of immune ageing in RA to date.

Researchers found that patients with early immune ageing features were more likely to develop RA. These findings could lead to the development of predictive tools that identify at-risk individuals and enable timely treatment.

“We’ve discovered that immune ageing isn’t just a consequence of rheumatoid arthritis—it may be a driver of the disease itself,” said Dr Niharika Duggal, senior author of the study and Associate Professor in Immune Ageing at the University of Birmingham. “We found that people in the early stages of rheumatoid arthritis ie, before a clinical diagnosis show signs of faster immune system ageing.

“These findings suggest we might be able to intercept the disease development in at-risk individuals and prevent it from developing by using treatments that slow ageing, such as boosting the body’s natural process for clearing out damaged cells (autophagy).”

Key Findings

  • Hallmarks of immune ageing, including reduced naïve T cells and thymic output, were observed in patients with early joint symptoms.
  • An elevated IMM-AGE score revealed accelerated immune ageing in patients before RA diagnosis.
  • Elevated levels of inflammatory markers (such as IL-6, TNFα, and CRP) were found in preclinical stages.
  • Advanced ageing features, including senescent T cells and inflammatory Th17 cells, appeared only after RA was fully established.

The study suggests that targeting ageing pathways could offer new strategies to prevent RA. Future research should determine whether geroprotective drugs such as spermidine (autophagy booster), senolytics (clearance of senescent cells) and metformin (attenuates inflammation and boosts autophagy) may help slow or halt disease progression in high-risk individuals.

Source: University of Birmingham

Categories : Exercise RheumatologyTags :

Exercise Breakthrough Offers Relief for People with Rheumatoid Arthritis

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The novel exercise involves applying a pneumatic cuff to restrict the flow of blood. Credit: University of South Australia

New research from the University of South Australia is offering fresh hope to people living with rheumatoid arthritis (RA).

Evaluating the effectiveness of a novel form of exercise – blood flow restricted resistance training – among people with RA, researchers found that this alternative workout method not only improved their strength and physical performance, but also reduced their pain.

Blood flow restricted resistance training involves placing a pneumatic cuff – much like a blood pressure cuff – around the top of the working limb. The cuff is then inflated so that it restricts blood flow out of the limb, creating a highly metabolic environment which forces the muscles to work harder, even when using lighter weights or less effort.

The Arthritis Australia-funded study is the first to trial blood flow restricted resistance training on both the upper and lower limbs in people with RA, using five exercises – leg press, machine hamstring curl, machine knee extension, cable tricep extension, and cable bicep curl – with gradually increasing weights.

All participants in the study reported that they “liked” the programme, and the group showed clear improvements in strength, movement and pain levels.

Lead researcher UniSA’s Dr Hunter Bennett says the training offers a practical and achievable option for people with RA.

“RA can cause a loss of muscle mass and strength, which affects day-to-day activities, independence, and increases the risk of falls and fractures,” he says.

“Resistance training is one of the best ways to rebuild that strength, but for people with RA, using heavy weights can be difficult or harmful due to pain, fatigue or injury risk. This is where blood flow restricted resistance training can help.”

Dr Bennett says this approach is ideal for people who need to do resistance exercises but find it hard to lift weights.

“Many people with health conditions are understandably deterred by exercise, yet it is often one of the best things they can do to improve their condition,” he says.

And while this exercise might look unusual, the research shows that it works.

“This kind of training could be a game-changer for people with rheumatoid arthritis.

“It offers a way to build strength and reduce pain without pushing through discomfort – and that’s incredibly empowering for people who’ve often been limited by their condition.”

While this was a small-scale trial, researchers say the results are promising and lay the foundations for a larger trial comparing blood flow restricted resistance exercise to more traditional exercise approaches.

Source: University of South Australia

Categories : Skeletal SystemTags :

Discovery of New Skeletal Tissue Holds Promise for Regenerative Medicine

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“Lipocartilage” is a type of supportive skeletal tissue, that consists of densely packed, bubble-like cells containing fat. This image shows a scan of mouse ear lipocartilage stained with a green fluorescent dye. Charlie Dunlop School of Biological Sciences

An international research team led by the University of California, Irvine has discovered a new type of skeletal tissue that offers great potential for advancing regenerative medicine and tissue engineering.

Most cartilage relies on an external extracellular matrix for strength, but “lipocartilage,” which is found in the ears, nose and throat of mammals, is uniquely packed with fat-filled cells called “lipochondrocytes” that provide super-stable internal support, enabling the tissue to remain soft and springy – similar to bubbled packaging material.

The study, published in the journal Science, describes how lipocartilage cells create and maintain their own lipid reservoirs, remaining constant in size. Unlike ordinary adipocyte fat cells, lipochondrocytes never shrink or expand in response to food availability.

“Lipocartilage’s resilience and stability provide a compliant, elastic quality that’s perfect for flexible body parts such as earlobes or the tip of the nose, opening exciting possibilities in regenerative medicine and tissue engineering, particularly for facial defects or injuries,” said corresponding author Maksim Plikus, UC Irvine professor of developmental and cell biology. “Currently, cartilage reconstruction often requires harvesting tissue from the patient’s rib – a painful and invasive procedure. In the future, patient-specific lipochondrocytes could be derived from stem cells, purified and used to manufacture living cartilage tailored to individual needs. With the help of 3D printing, these engineered tissues could be shaped to fit precisely, offering new solutions for treating birth defects, trauma and various cartilage diseases.”

Dr Franz Leydig first recognised lipochondrocytes in 1854, when he noted the presence of fat droplets in the cartilage of rat ears, a finding that was largely forgotten until now. With modern biochemical tools and advanced imaging methods, UC Irvine researchers comprehensively characterised lipocartilage’s molecular biology, metabolism and structural role in skeletal tissues.

They also uncovered the genetic process that suppresses the activity of enzymes that break down fats and reduce the absorption of new fat molecules, effectively locking lipochondrocytes’s lipid reserves in place. When stripped of its lipids, the lipocartilage becomes stiff and brittle, highlighting the importance of its fat-filled cells in maintaining the tissue’s combination of durability and flexibility. In addition, the team noted that in some mammals, such as bats, lipochondrocytes assemble into intricate shapes, like parallel ridges in their oversized ears, which may enhance hearing acuity by modulating sound waves.

“The discovery of the unique lipid biology of lipocartilage challenges long-standing assumptions in biomechanics and opens doors to countless research opportunities,” said the study’s lead author, Raul Ramos, a postdoctoral researcher in the Plikus laboratory for developmental and regenerative biology. “Future directions include gaining an understanding of how lipochondrocytes maintain their stability over time and the molecular programs that govern their form and function, as well as insights into the mechanisms of cellular aging. Our findings underscore the versatility of lipids beyond metabolism and suggest new ways to harness their properties in tissue engineering and medicine.”

Source: University of California – Irvine

Categories : Implants and Prostheses Skeletal SystemTags :

Study Identifies Hip Implant Materials with Lowest Risk of Revision

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Photo by DanR on Flickr

Hip implants with a delta ceramic or oxidised zirconium head and highly crosslinked polyethylene liner or cup had the lowest risk of revision during the 15 years after surgery, a new University of Bristol-led study has found. The research could help hospitals, surgeons and patients to choose what hip implant to use for replacement surgery.

The aim of the study, which appears in PLOS Medicine, was to establish hip implant materials at risk of revision. This would help orthopaedic surgeons, and patients, and to improve shared decision making before surgery by identifying hip implants with the lowest risk of revision.

The researchers analysed the UK’s National Joint Registry (NJR) data from 1 026 481 hip replacement patients carried out in the NHS and private sectors in England and Wales for up to 15 years after initial hip replacement operations (between 2003 to 2019). 

After reviewing hip implants from the NJR data, the research team found the risk of revision following a hip replacement is influenced by the type of material used in the bearing surface. Bearing surfaces are the moving parts of an artificial hip joint that glide against each other during activity.

The data indicated that hip implants with a delta ceramic or oxidised zirconium head and highly crosslinked polyethylene liner or cup had the lowest risk of revision throughout the 15 years following hip replacement surgery.

These findings were confirmed when the research team investigated the specific reasons for revision hip replacements being performed.  The data also showed 20 869 (2%) of hip replacement patients had to undergo revision after the initial surgery.

Senior author Dr Erik Lenguerrand, Senior Lecturer in Medical Statistics and Quantitative Epidemiologist in the Bristol Medical School: Translational Health Sciences (THS), said: “Our research has found the risk of hip replacement revision depends on the hip implant materials used in the original surgery.  The lowest risk of revision are from implants with delta ceramic or oxidised zirconium head and a highly crosslinked polyethylene (HCLPE) liner or cup.

“Further research is needed to find out the association of implant materials with the risk of rehospitalisation, re-operation other than revision, mortality and the cost-effectiveness of these materials.”

Michael Whitehouse, Professor of Trauma and Orthopaedics at Bristol Medical School: THS, and senior clinical lead for the paper, explained: “Our study has used data from one of the largest registries in the world that includes all public and private health care sectors in England and Wales. This means that the data is more generally applicable than that available previously, which was limited by broad groupings of implant types or much smaller study size. It highlights the importance of considering the whole structure that is created when implants are put together to make up a hip replacement rather than focusing on individual components.

“Our findings will help hospitals, surgeons and patients to choose hip implants and combinations of them with the lowest risk of revision following an initial hip replacement operation.”

Tim Wilton, Medical Director of the National Joint Registry (NJR), added: “We are always delighted when the data from the NJR can be used by researchers to produce important research of this kind which gives meaningful analysis to guide surgeons and patients in their decisions. An important value of the NJR data is that it allows researchers a unique insight to assess the long-term performance of different hip implant materials.

“By tracking the combinations of materials used and subsequent revision rates, this research highlights the role of implant material choice in surgical outcomes. This ensures that the materials used can be optimised for longevity and patient health. Surgeons would be well advised to study these findings carefully in relation to the implant choices they make, and to use the information in pre-operative discussions with their patients. As the demand for joint replacements continues to rise, this insight can be invaluable in reducing revision surgery.”

The research was not a randomised controlled trial and therefore it was not possible to control all factors that can influence the risk of revision.

The categorisation of hip implants used as part of hip replacements is often broad in national joint replacement surgery registries and does not fully show differences in revision risks associated within the different types of implant materials grouped together.

Source: University of Bristol

Categories : GastrointestinalTags :

Gut Health Signals could Transform Arthritis Treatment

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Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

Changes in the gut microbiome before rheumatoid arthritis is developed could provide a window of opportunity for preventative treatments, new research suggests.

Bacteria associated with inflammation is found in the gut in higher amounts roughly 10 months before patients develop clinical rheumatoid arthritis, according to a longitudinal study by researchers at the University of Leeds. 

This new research might give us a major opportunity to act sooner to prevent rheumatoid arthritis.

Dr Christopher Rooney, Leeds Institute of Medical Research

Previous research has linked rheumatoid arthritis to the gut microbiome, which is the ecosystem of microbes in your intestines. But this new study, published in the Annals of the Rheumatic Diseases, reveals a potential intervention point. 

Lead researcher Dr Christopher Rooney, NIHR Academic Clinical Lecturer at the University of Leeds and Leeds Teaching Hospitals NHS Trust, said: “Patients at risk of rheumatoid arthritis are already experiencing symptoms such as fatigue and joint pain, and they may know someone in their family who has developed the disease. As there is no known cure, at-risk patients often feel a sense of hopelessness, or even avoid getting tested.  

“This new research might give us a major opportunity to act sooner to prevent rheumatoid arthritis.” 

Major opportunity for treatment

Funded by Versus Arthritis, the longitudinal study was conducted on 19 patients at risk of rheumatoid arthritis, with samples taken five times during a 15-month period.  

Five of these patients progressed to clinical arthritis, and the research showed they had gut instability with higher amounts of bacteria including Prevotella, which is associated with rheumatoid arthritis, about ten months before progression. The remaining 14, whose disease didn’t progress, had largely stable amounts of bacteria in their gut. 

Potential treatments that the researchers want to test at the 10-month window include changes to diet like eating more fibre, taking prebiotics or probiotics, and improving dental hygiene to keep harmful bacteria from periodontal disease away from the gut. 

The exact relationship between gut inflammation and rheumatoid arthritis development remains unclear. In a small number of patients within the study, the gut changes occurred before there were any changes to the joints observed by a rheumatologist, but more research is needed to determine whether these influence each other. 

Although bacteria is associated with rheumatoid arthritis, the researchers want to make it clear that there is no evidence this is contagious. 

Lucy Donaldson, director for research and health intelligence at Versus Arthritis, said: “At Versus Arthritis, we welcome the findings of this study which could give the clinicians of the future a crucial window of opportunity to delay – or even prevent – the onset of rheumatoid arthritis. This success is testament to the dedication of UK researchers who are working to personalise treatment and prevent chronic conditions that have significant impacts on a person’s ability to work, raise families and live independently.” 

The study initially took data from 124 individuals who had high levels of CCP+, an antibody that attacks healthy cells in the blood, which indicates risk of developing rheumatoid arthritis. The researchers compared their samples to 22 healthy individuals and seven people who had a new rheumatoid arthritis diagnosis.  

The findings from this larger group showed that the gut microbiome was less diverse in the at-risk group, compared to the healthy control group. 

The longitudinal study, which took samples from 19 patients over 15 months, revealed the changes in bacteria at ten months before progression to rheumatoid arthritis. 

The Leeds research team will now carry out an analysis of treatments that have already been trialled, to inform future testing of treatments at this potential 10-month intervention point. 

Source: University of Leeds

Categories : New Compounds and TreatmentsTags :

Abatacept may Hold Back Progression of Rheumatoid Arthritis

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Photo by Towfiqu barbhuiya

Results from a Phase 2b clinical trial, published in The Lancet, provides hope for arthritis sufferers after it was shown that the biologic drug abatacept reduces progression to this agonising chronic inflammatory disease.

Rheumatoid arthritis is an autoimmune condition that typically (but not always) starts in middle age, with joint pain, swelling and significant disability. Until now there is no cure or prevention.

Abatacept is currently used as an effective second or third line treatment for people living with established rheumatoid arthritis and is given by weekly injections at home or intravenously in hospital.

Researchers from King’s College London recruited 213 patients at high risk of the disease to understand whether a year-long treatment of the biologic drug could be used to prevent progression to rheumatoid arthritis.

They recruited men and women over the age of 18 with early symptoms such as joint pain but no joint swelling, and treated half with the drug and half with a placebo every week for a year. The study drug was then stopped, and study participants monitored for a further 12 months.

After twelve months of treatment, 6% of patients treated with abatacept had developed arthritis compared to 29% in the placebo arm. By 24 months, the differences were still significant, with a total of 25% progressing to rheumatoid arthritis in the abatacept arm compared to 37% in the placebo arm.

Secondary outcomes for the trial showed that abatacept was associated with improvements in pain scores, function and quality of life measurements, as well as lower scores of inflammation of the lining of joints detectable by ultrasound scan.

Professor Andrew Cope, Professor of Rheumatology from School of Immunology & Microbial Sciences, said: “This is the largest rheumatoid arthritis prevention trial to date and the first to show that a therapy licensed for use in treating established rheumatoid arthritis is also effective in preventing the onset of disease in people at risk.

“These initial results could be good news for people at risk of arthritis as we show that the drug not only prevents disease onset during the treatment phase but can also ease symptoms such as pain and fatigue. This is also promising news for the NHS as the disease affects people as they age and will become more expensive to treat with a growing aging population.”

Philip Day, a 35-year-old software engineer and founder of FootballMatcher from Eltham, was at high-risk for rheumatoid arthritis. A keen football player, Philip’s joint pain deterred him from playing and affected his day-to-day life. He was enrolled in the trial in 2018, at the age of the 30, and was prescribed abatacept.

He said: “The pain got so terrible I stopped going to football, and I got lazier and felt progressively worse physically and mentally. The pain was unpredictable, it would show up in my knees one day, my elbows the next, and then my wrists or even my neck. At the time, my wife and I wanted to have children and I realised my future was pretty bleak if the disease progressed. I’d always wanted to be the kind of dad that played football with his son and I knew the pain would stop me from realising that dream.

“Enrolling in the trial was a no-brainer; it was a ray of hope at a dark time. Within a few months I had no more aches or pains and five years on I’d say I’ve been cured. Now, I can play football with my three-year-old son and have a normal life.”

One year’s treatment with abatacept costs the NHS about £10 000 (ZAR 238 000) per patient. Side effects include upper respiratory tract infections, dizziness, nausea and diarrhoea, but these are generally mild.

Professor Cope added: “There are currently no drugs available that prevent this potentially crippling disease. Our next steps are to understand people at risk in more detail so that we can be absolutely sure that those at highest risk of developing rheumatoid arthritis receive the drug.”

Source:

Categories : Cardiovascular DiseaseTags :

Potential New Treatment to Reverse Inflammation and Atherosclerosis in Rheumatoid Arthritis

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Image by Scientific Animations, CC4.0

Researchers from Queen Mary University of London have found that the molecule RvT4 enhances the body’s natural defences against atherosclerosis in patients with rheumatoid arthritis.

The mouse-based study, published in Nature Communications, shows that increasing levels of the RvT4 molecule in the body improves the ability of the body’s own defence mechanisms [macrophages] to reduce local inflammation and remove blockages in blood vessels.

This breakthrough in understanding the processes involved could lead to better treatments for people who have rheumatoid arthritis (RA), and who are at higher risk of developing cardiovascular disease.

Alongside the more widely-known symptoms of joint inflammation, people with the condition are also twice as likely as others to develop blood vessel disease.

One type of blood vessel disease seen in people with RA is atherosclerosis, which is caused by a build-up of ‘plaque’ along the artery walls, which can break free and cause heart attacks and strokes.

Understanding the reasons why RA patients are at increased risk of these cardiovascular problems is critical in developing better treatments for this group and others.

To gain a better understanding of the causes of blood vessel disease in patients with RA, researchers explored the role of a group of molecules called 13-series resolvins (RvTs). In experimental arthritis the levels of one of these molecules, RvT4, are markedly reduced, a phenomenon that associates with a higher degree of blood vessel disease.

This study was designed to explore why this might be the case.

The findings

The study found that treating arthritic mice with RvT4 reduced blood vessel inflammation by re-programming macrophages, which accumulate in the diseased vessels, to release stored lipids.

Researchers observed that these lipids were preventing the macrophage from carrying out their usual work of clearing dead cells and reducing localised inflammation in blood vessels.

Once freed of their lipid burden, the macrophages were able to move and work much more effectively to reduce the causes of atherosclerosis.

The observation that RvT4 restores protective macrophage biological activities is an exciting finding.

RA patients also often present with metabolic dysfunction and this is thought to exacerbate vascular disease.

The study found that administration of RvT4 to mice engineered to develop characteristics of metabolic dysfunction, advanced atherosclerosis, and arthritis led to an overall decrease in lipoprotein-associated cholesterol in plasma and an increase in the ratio of HDL-associated cholesterol to total cholesterol.

Jesmond Dalli, Professor in Molecular Pharmacology and Lipid Mediator Unit Director at the William Harvey Institute, Queen Mary University of London, said: “The study is important because it identifies for the first time the loss of RvT4 production as a potential new cause of blood vessel inflammation in the context of arthritis, offering a mechanistic explanation on the cause of this important disease in RA patients. It also showed that RvT4 restores the biological activities of lipid loaded macrophages by promoting lipid breakdown and efflux from the cells, an observation that can guide the development of new treatments to limit the incidence and/or severity of cardiovascular disease in patients with RA.”

Source: Queen Mary University of London

Categories : Immune SystemTags :

Immunomodulatory Rheumatoid Arthritis Drugs might Prevent Autoimmune Thyroid Disease

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Source: Pixabay

Anti-rheumatic drugs used for rheumatoid arthritis (RA) might prevent the development of autoimmune thyroid disease, according to a new observational study by researchers from Karolinska Institutet which is published in the Journal of Internal Medicine.   

Patients with RA at increased risk of autoimmune thyroid diseases such as Hashimoto’s disease and Graves’ disease. While patients with RA are usually treated with immunomodulatory drugs that affect the immune system, such drugs are rarely used in autoimmune thyroid diseases. Instead, such patients are treated with thyroid hormones such as levothyroxine to compensate for the changes in normal thyroid function that accompany autoimmune thyroid disease.  

In this study, the researchers wanted to investigate whether immunomodulatory drugs that reduce inflammation in the joints of patients with RA might also reduce the risk of these patients developing autoimmune thyroid disease. Previous studies in mice suggest that so-called DMARDs, a type of immune-modulatory drugs used to treat rheumatoid arthritis, can reduce inflammation in the thyroid gland. Still, knowledge of whether this effect also applies to humans is limited, according to the research team.   

The researchers used data between 2006 and 2018 on over 13 000 patients with rheumatoid arthritis and their treatment, as well as data from over 63 000 individuals in a matched control group without rheumatoid arthritis.  

The researchers found that the risk of developing an autoimmune thyroid disease among RA patients was lower after their onset of the rheumatic disease than before diagnosis.  

The most greatest risk reduction was seen in RA patients treated with immunomodulatory drugs or ‘biological DMARDs’. In these patients, the risk of autoimmune thyroid disease was 46% lower than in the control group without rheumatoid arthritis.   

“These results support the hypothesis that certain types of immunomodulatory drugs could have a preventive effect on autoimmune thyroid disease,” says Kristin Waldenlind, researcher at the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, specialist in rheumatology at Karolinska University Hospital and first author of the study. She continues:  

“Our results do not prove that it is the treatment with immunomodulatory drugs that led to the reduced risk of autoimmune thyroid disease, but provide support for this hypothesis. The results, if they can be replicated in further studies, open up the possibility of studying more directly in clinical trials whether the immunomodulatory drugs currently used for rheumatoid arthritis could also be used for the early treatment of autoimmune thyroid disease, ie for new areas of use of these drugs, known as drug repurposing.”

Source: Karolinksa Institutet

Categories : Ageing Immune SystemTags :

New Approach May Take the Guesswork out of Selecting Treatments for RA

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Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/

New research reported in the journal Nature could lead to new targeted treatments for rheumatoid arthritis (RA). The findings showed that guesswork could be taken out of selecting treatments for each patient, and this might one day also be extended to other autoimmune conditions.

The study was led by University of Colorado School of Medicine faculty members Fan Zhang, PhD, and Anna Helena Jonsson, MD, PhD. The Accelerating Medicines Partnership: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP: RA/SLE) Network collected inflamed tissue from 70 patients with RA from across the country and the United Kingdom. Jonsson supervised the team of scientists who processed these samples for analysis, and Zhang led the computation analysis of the data. These efforts yielded a cell atlas encompassing more than 300 000 cells from synovial tissue. Further analysis revealed that there are six different subgroups of RA based on their cellular makeup.

“We hope the data will help us discover new treatment targets,” says Jonsson, assistant professor of rheumatology. “We wanted to make it public so that researchers across the country and across the world can continue working on new treatment ideas for rheumatoid arthritis going forward.”

No more guess-and-check

Jonsson, a practicing rheumatologist as well as a researcher, knows that RA patients respond differently to different treatments. Until now, she says, rheumatologists used a “guess and check” method to find a treatment that works for an individual patient.

With the new data and powerful computational classification methods developed by Zhang and the computational analysis team, the researchers were able to quantitatively classify RA types into what they call ‘cell-type abundance phenotypes’, or CTAPs. Developed methods, together with the new cell atlas, can start to identify which patients will respond to which treatments.

“Even when you classify rheumatoid arthritis inflammation using these simple markers – T cell markers, B cells, macrophages and other myeloid cells, fibroblasts, endothelial cells – what we found is that each of those categories is associated with very specific kinds of pathogenic cell types we’ve already discovered,” Jonsson says. “Previous rheumatoid arthritis research found that T cell populations called peripheral helper T cells are relevant in rheumatoid arthritis, as are B cells called antibody-producing B cells, and other specific cell types. What we found is that they’re usually not found all together.

“For example, the peripheral helper cells are found with the B cells in only one category of RA, and the pathogenic macrophage populations tend to exist in a different category. Because of this, we can start asking questions about how these specific partners work together.”

Source: University of Colorado Anschutz Medical Campus

Categories : AgeingTags :

Immunomodulator Keeps Subclinical Arthritis from Developing into Full-blown Form

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Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/

In a 12-month trial involving patients with “preclinical” rheumatoid arthritis, treatment with the immunomodulator abatacept (Orencia) kept the condition from becoming clinical, according to findings presented at the European Alliance of Associations for Rheumatology (EULAR) annual meeting.

Rheumatologists have long sought to nip rheumatoid arthritis (RA) in the bud, with many studies supporting early aggressive treatment on RA diagnosis. This has never been recommended for biologic therapies however.

Nevertheless, some patients show up at arthritis clinics with a few painful joints and other features such as RA-related serum biomarkers that suggest progression to full-blown RA is likely. Would aggressive treatment help slow their decline into RA?

In a phase IIb randomised trial involving patients in the UK and Netherlands who were at high risk for developing RA, only seven of the 110 assigned to abatacept had gone on to develop clinical arthritis after 1 year, compared with 30 of 103 in a placebo group.

The effect waned after abatacept was stopped at the one-year mark, and in the following year, 20 more patients in the abatacept group developed clinical arthritis, as did another eight in the placebo group.

Though the abatacept regimen held the edge for a full two years, projections showed that it was likely that the abatacept group would catch up with additional follow-up. At the same time, abatacept had no particular safety issues and thus could likely be continued.

A decade ago, Andrew Cope, MD, MBBS, of King’s College London colleagues thought about aggressive prevention, registering the current trial, Arthritis Prevention in the Pre-clinical Phase of RA with Abatacept (APIPPRA), in 2014. In a 2019 description of the protocol, they explained the selection of abatacept because “it targets immune reactions early in the chain of events leading to inflammation in RA. It functions by interrupting the interaction between T cells and antigen-presenting cells, attenuating the co-stimulatory signals required for T-cell activation, differentiation and effector responses,” thereby resulting “in downstream immunomodulatory effects on other inflammatory cells of the immune system.”

Participants had to show joint pain but no synovitis, plus either test positive for anti-citrullinated protein antigen (ACPA) antibodies and for rheumatoid factor (RF), or show high levels of ACPA antibodies without RF. The primary endpoint was development of clinically apparent arthritis in at least three joints or diagnosis of RA according to standard criteria.

While the preventive effect seen in the primary analysis did not hold up across the whole sample, Cope noted that it appeared more so in one very-high-risk subgroup: 49 patients who had some level of IgG ACPA antibodies and who were also positive for a series of other biomarkers, including RF, IgA ACPA antibodies, anti-carbamylated protein antibodies, and anti-acetylated peptide antibodies. For this subgroup, only about 10% of those who had taken abatacept progressed to clinical arthritis after two years, versus 50% of those assigned to placebo.

Source: MedPage Today