Towards Early diagnosis and biomarker validation in Arthritis Management
EuroTEAM Arthritis (Towards Early diagnosis and biomarker validation in Arthritis Management) is a challenging research project, funded by the European Union with 5.77 Million Euro for four years. Clinicians and lab scientists with world class expertise in rheumatoid arthritis research from 13 renowned European research institutions and three industrial partners with competence in design and development of diagnostic test kits for autoimmune diseases, local gene therapy for rheumatic diseases, and human genome analysis join their efforts in the discovery of novel biomarkers for early detection of rheumatoid arthritis. The EuroTEAM members intend to develop approaches to predict the onset of rheumatoid arthritis in people who do not yet have the disease. Ultimately, this will help in the development of treatments to prevent people from getting rheumatoid arthritis.
Rheumatoid factor (RF) is one of the best known serological markers in rheumatology – development of the test dates back into the 1940ies. Since this time the toolkit of serological diagnostic tests for rheumatoid arthritis (RA) has been complemented by the more specific anti-citrullinated protein antibody (ACPA) tests. However, none of the various ACPA tests has completly replaced RF until now.
The jigsaw puzzle of rheumatoid arthritis classification
In contrast, the significance of RF has been further substantiated with the definition of the 2010 ACR criteria for classification of RA. Moreover, recent studies have shown the potential of RF as a contributor to disease pathogenesis.
Inflammatory rheumatic diseases predominantly affect women. This also includes many young women who would like to have children or who have not yet completed their family planning when they are first diagnosed. These women do not need to give up on their desire to have children forever. Women with rheumatic disease tend to have fewer children than other women, and it often takes them longer to achieve a desired pregnancy. Today, carefully monitored medical treatment and close collaboration between the rheumatologist and the gynaecologist give these women the opportunity to bring a healthy child into the world.
Linking autoantibody production to bone loss
in rheumatoid arthritis
Autoantibodies against citrullinated proteins (ACPA) are found in people with rheumatoid arthritis and are one of the strongest risk factors for bone destruction in this disease. A recent study now directly links the formation of antibodies binding to mutated citrullinated vimentin (anti-MCV) to bone loss in rheumatoid arthritis, indicating that these autoantibodies act on osteoclasts, the bone cells responsible for bone resorption.
Harre U, Georgess D, Bang H, Bozec A, Axmann R, Ossipova E et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest 2012; 122(5):1791-802. (1)
The research of U. Harre, G. Schett and their coworkers provides fundamental new insights into the interaction between bone and the immune system in the inflammatory process leading to the development of rheumatoid arthritis.
In rheumatoid arthritis, standard heart disease risk tools underrate danger!
Patients suffering from rheumatoid arthritis, or RA for short, are at higher risk for heart disease. Among experts that’s a matter of common knowledge (fortunately and increasingly that is basic knowledge among patients, too!).
Watch out, doctors! – In elderly rheumatoid arthritis patients commonly used heart disease risk assessment tools regularly fail, according to a current study. – © Robbie Ribeiro
On a less positive note, commonly used heart disease risk assessment tools seem to be inadequate for estimating the risk of cardiovascular disease danger faced by RA patients. That is what a brand-new study found.
In this blog article I summarise the main results of the research done at Mayo Clinic in Rochester, Minnesota (USA). The study is entitled Usefulness of Risk Scores to Estimate the Risk of Cardiovascular Disease in Patients With Rheumatoid Arthritis, and it has been published online on 20th April 2012 in The American Journal of Cardiology.
Heart disease risk in RA: More accurate assessment tools needed
The study estimated the accuracy of the Framingham and Reynolds risk scores, two tools commonly used by physicians for assessing patients’ heart disease danger. The scientists found that these two assessment tools substantially underrated cardiovascular disease danger both in women and men suffering from rheumatoid arthritis. In particular, that happens in older patients. Interestingly enough, it also happens in people who test positive for rheumatoid factors. (more…)
The long Arm of the Dendritic Cells: The Link between Atherosclerosis and Autoimmune Diseases
Inflammation has been closely linked to autoimmunogenic processes in atherosclerosis. In fact, patients who are suffering from an autoimmune disease have an increased incidence of “hardening of the arteries”, concretely atherosclerosis (the spelling “arteriosclerosis” is also common). In the case of rheumatoid arthritis (RA) the patients have a 30 to 60% higher risk of suffering a heart attack or stroke!
It is an accepted fact: Rheumatoid arthritis patients have a higher risk of suffering a heart attack or stroke. But where is the connection between the two types of disease?
pDCs: the link between atherosclerosis and autoimmunity
Now clinical researchers at Munich Ludwig-Maximilians-University (LMU) have uncovered a mechanism which establishes a causal link between the two types of disease. The immunological process may help to explain the link between autoimmunity and atherosclerosis.
The mechanism described is provided by a specific class of immune cells called plasmacytoid dendritic cells (pDCs). The pDCs respond to DNA released from damaged and dying cells by secreting interferon proteins. The research, which is done in collaboration with scientists from Rudolf Virchow Center at Wuerzburg University, shows that stimulation of pDCs by a specific DNA-protein complex contributes to the progression of atherosclerosis. These findings may have implications for new strategies for the treatment of a whole spectrum of conditions that are associated with chronic inflammatory reactions. (more…)
Anti-CCP hs (high sensitive)®: a new biomarker for the serological diagnosis of early rheumatoid arthritis
Timely diagnosis is of critical importance to the progression of rheumatoid arthritis (RA) because the rapid implementation of intensive treatment can inhibit damage to the joints and maintain function. In conjunction with medical history, clinical examination, and imaging procedures, serological tests form the foundation for an early diagnosis.
In addition to rheumatoid factors, autoantibodies against citrullinated antigens (ACPA) have proven to be valuable tools for the serological diagnosis of early RA. They have become a critical component of the new 2010 ACR criteria for the classification of RA, and account for three of the six points required to verify a diagnosis of RA. (more…)
No matter if it’s rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or multiple sclerosis (MS): most autoimmune diseases affect women significantly more often than men. It is possible that this could be at least partially explained by the occurrence of age-associated B cells (ABCs), as described in an article recently published in Blood, the journal of the American Society of Hematology. (more…)
According to a recent study, a new biomarker may make it possible to make a prognosis regarding the progression of the autoimmune disease rheumatoid arthritis (RA).
The results of the study, which was carried out at the University of Munich Clinics, were recently published in the Annals of the Rheumatic Diseases, The EULAR Journal. At the centre of this study lies an analysis of the cell hormone interleukin-22, IL-22, and its significance as a prognostic marker for RA. The researchers examined the relationship between the serum levels of interleukin-22 and the risk of bone erosion and joint damage in RA patients. (more…)
Antibodies to Modified Citrullinated Vimentin Are Associated with Subclinical Atherosclerosis in Early Rheumatoid Arthritis
Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease (CVD), especially accelerated atherosclerosis (1-3). There is evidence that this already occurs early in the disease process. Well known common CVD risk factors interact with the systemic auto-inflammatory response during the disease process and speed up the development of atherosclerosis in patients suffering from rheumatoid arthritis.
Antibodies against citrullinated protein and peptide antigens (ACPA) are highly sensitive and specific markers for early rheumatoid arthritis. Antibodies to Modified Citrullinated Vimentin (anti-MCV) predict poor outcome and appear to play a major role in the pathogenesis of rheumatoid arthritis.
A recently published study by Amal El-Barbary and his co-workers may now shed light on the relationship between anti-MCV antibodies and cardiovascular co-morbidities in patients with rheumatoid arthritis (4). They investigated the correlation of anti-MCV antibodies in early RA with disease activity and cardiovascular risk factors compared to antibodies against cyclic citrullinated peptides (anti-CCP3). (more…)