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.
The famous musician Seal is known for his numerous international hits, and for living with an autoimmune disease: the scars on his face are the result of discoid lupus erythematosus. Picture: C. Grube for Access2music.de, wikimedia
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with manifold manifestations. SLE belongs to the family of autoimmune disorders, diseases that occur, when a mislead immune system attacks the body’s own structures. SLE can affect almost any organ system, thus its presentation and course are highly variable, and diagnosis and therapy may be challenging.
With the intention to classify SLE patients for research and surveillance studies and to support clinicians in confirming a diagnosis, a set of clinical and laboratory classification criteria has been developed and released by the American College of Rheumatology (ACR). The first classification criteria for SLE were originally published in 1971 [1,2]. They have been updated 1982  and 1997  to incorporate new immunologic knowledge and improve patient classification. In contrast to the 1987 criteria, the 1997 criteria have not been validated.
The most recent addendum to the classification criteria for SLE dates from 2012, when the Systemic Lupus International Collaborating Clinics (SLICC) group published a revision and validation of the ACR criteria .
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.
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:
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…)
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…)
Celiac disease diagnostics revised
Anti-endomysial antibodies on monkey esophagus
The diagnostic criteria for celiac disease (CD) have remained unchanged for more than 20 years, after the 1990 revision of the guidelines originally formulated in 1969. During this period the disease has been intensively studied and scientific findings have unveiled the genetic background of celiac disease, linked to the human leukocyte antigen (HLA)-DQ2 and HLA-DQ8 haplotypes. The key autoantigen tissue transglutaminase (tTG) has been identified and reliable laboratory tests for disease specific autoantibodies now contribute to diagnostics and complement the methodological repertoire of clinical observations and histologic findings in duodenal biopsy samples. Finally, the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has now published New Guidelines for the Diagnosis of Celiac Disease.