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.
May measuring of fecal calprotectin replace colonoscopy for follow up of patients with Crohn’s disease after surgery?
After intestinal resection patients with Crohn’s disease need close monitoring and tailored therapy adjustment to reduce the risk of relapses. Today, colonoscopy is still the gold standard for the detection of disease reactivation, an invasive procedure which is unpleasant for the patient and expensive for the health care systems.
Biomarkers in blood or stool samples that correlate with endoscopic findings could therefor improve the surveillance of patients with inflammatory bowel diseases.
A candidate marker for this purpose is measurement of calprotectin concentrations in stool samples from affected patients.
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.
Differential diagnosis of bowel diseases can be challenging, because most of them present with similar common symptoms: abdominal pain and discomfort, diarrhea, weight loss. Infections by common gastrointestinal pathogens may soon be identified, but discrimination of inflammatory bowel disease, of which ulcerative colitis and Crohn’s disease are the most common, and irritable bowel syndrome, remains difficult.
Inflammatory bowel disease (IBD) is characterised by inflammation of the bowel, which is not seen in most patients with irritable bowel syndrome (IBS), and both conditions request different diagnostic and therapeutic approaches. IBD are serious diseases with severe comorbidities, and affected patients need further investigation with extensive diagnostic measures and intensive medical treatment. In contrast to that, IBS may be painful and impairs quality of life, but it does not usually cause serious morbidity. However, patients with IBS can have symptoms for many years and they often experience unnecessary and stressing diagnostic procedures.
Anti-Centromere B on HEp2 cells
HEp2 cells are held dear in autoimmune diagnostics. They are invaluable for people engaged in analysing autoantibodies, as E. coli is for molecular biologists or mice for toxicologists.
In spite of a wide range of other suitable methods and technologies, determination of autoantibodies with indirect immuno-fluorescence assays (IFA) on human epithelioma (HEp2) cells still contributes significantly to the diagnosis of autoimmune diseases. The widely recognised advantages of this method are high sensitivity and a broad spectrum of antibodies that can be analysed simultaneously. In addition to mere detection of antibodies a characteristic fluorescence pattern and staining of metaphase and cytoplasmic cells offer supplementary information.
When an autoimmune disease is suspected, the HEp-2 test usually is the first line test. Any positive result is then followed up by a step-wise diagnostic approach, including other immunological tests like ELISA (enzyme-linked immunosorbent assay) for single antibody specificities or immunoblot tests.
The web community GRÜNER CLUB AUTOIMMUN is a voluntary association of scientists, laboratory specialists, medical doctors, students and immunofluorescence enthusiasts from Austria. In their internet blog these experienced IFT professionals discuss questions, ideas and concepts of immunofluorescence tests in autoimmune disease diagnostics.
In a recent posting my Austrian colleague Barbara Fabian, community manager of GRÜNER CLUB AUTOIMMUN, refered to the relationship between the formation of autoantibodies against glomerular basal membrane (GBM) and ANCA (antibodies against cytoplasmic antigens of neutrophil granulocytes). The article was originally written in German language, but we had it translated for the not German speaking readers of the Autoimmunity Blog.
Autoantibodies against Glomerular Basal Membrane and Myeloperoxidase in Crescentic Glomerulonephritis
by Barbara Fabian, Vienna
Crescentic Glomerulonephritis (CGN) is an autoimmune disease of the kidney that leads to vasculitis of the capillaries in the glomeruli. The appearance of characteristic autoantibodies or antibody complexes is indicative of CGN and allows for the differentiation of three groups:
Recently, a new study has identified a couple of biomarkers that may predict disease progression in patients suffering from ankylosing spondylitis (or: AS for short), an autoimmune disease also called Morbus Bechterew.
The German study describes key inter-group differences between different types of AS patients, which may predict the progression of structural damage in the spine. In the future awareness of such differences will help physicians to stratify patients due to risk. Hence, the results may pave the way for developing specific treatment options for this autoimmune disorder.
New treatment options on the horizon
In the more recent past, several biomarkers have been described to be associated with radiographic spinal progression and syndesmophyte formation in Bechterew’s disease. However, it is not clear, whether these biomarkers are also able to predict new bone formation in AS patients.
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.
Since the early 1960s almost a dozen different criteria for Sjögren’s syndrome (SS) have been published, both for classifying and for diagnosing that autoimmune disease. Recently, an international team of rheumatologists has published new classification criteria for Sjögren’s syndrome. In the April issue of the Arthritis Care & Research journal the authors propose clear and carefully worded guidelines.
Without question, these “new 2012 classification criteria for Sjögren’s syndrome” are urgently needed to better support etiologic and genetic research and therapeutic trials for Sjögren’s syndrome. Indeed, the new criteria are the first to be based solely on objective clinical tests!
Many other criterions have permitted various testing subjectivity to enable the classification of the disorder. In consequence, subjectivity has made standardisation of clinical trial inclusion something of a moving target, limiting comparability of research data across studies and impeding the needed robust clinical evaluation of possible new treatments. But criteria used for enrollment into clinical trials need to be clear, be easy to apply. And the new 2012 criteria agree to that demand. (more…)
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…)