Breaking News
February 20, 2019 - Over Half of Hip Replacements Expected to Last 25 Years
February 20, 2019 - Microscopic eye movements affect how we see contrast
February 20, 2019 - Computer vs. patient: Fighting for residents’ attention | News Center
February 20, 2019 - New “Smart Drug” Shows Promise for Metastatic Triple-Negative Breast Cancer
February 20, 2019 - Researchers develop large-scale window material for high-efficiency PM2.5 capture
February 20, 2019 - Widespread confusion among consumers on food date labels lead to unnecessary discards
February 20, 2019 - Researchers unlock plant’s secret of producing specialized metabolites
February 20, 2019 - Newly released national framework identifies obstacles to improving EMS systems
February 20, 2019 - Exercise can shift human body clock depending on time when people work out
February 20, 2019 - Female adolescent blood donors more likely to have iron deficiency and related anemia
February 20, 2019 - Rubicon level linked to inhibition of autophagic process
February 20, 2019 - Researchers find potential therapeutic strategy to treat Alzheimer’s
February 20, 2019 - New forms of older anti-cancer agent appear to enhance immune response to fight melanoma
February 20, 2019 - Health Tip: Eat Less Saturated Fat
February 20, 2019 - Sleeping in contact lenses puts you at risk of dangerous infection
February 20, 2019 - “We should study that!”: How a nurse-scientist found her passion
February 20, 2019 - Cervical microbiome may influence HPV infection more than previously thought
February 20, 2019 - Sausage mislabeling in Canada is down, new study finds
February 20, 2019 - Study shows blood pressure benefits of morning exercise for older overweight/obese adults
February 20, 2019 - New screening method could catch organ rejection much earlier without a biopsy needle
February 20, 2019 - Study may have important implications for refining parenting during child’s adolescence
February 20, 2019 - Study sheds new light on how antibiotic resistance genes are transferred between bacteria
February 20, 2019 - Chronic Wasting Disease may soon spread to humans, warns CDC
February 20, 2019 - Scientists identify new genetic causes linked to abnormal pregnancies and miscarriages
February 20, 2019 - Using LyoSpeed technology to avoid residual solvent when drying HPLC fractions
February 20, 2019 - Scientists join forces to identify a new approach to fight African sleeping sickness
February 20, 2019 - New screening tool more likely to identify sexual and labor exploitation of youth
February 20, 2019 - Newly licensed nurses work for long hours, also have a second paid job
February 20, 2019 - Physicists identify simple mechanism used by deadly bacteria to fend off antibiotics
February 20, 2019 - FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib
February 20, 2019 - Exposure to chemicals before and after birth is associated with a decrease in lung function
February 20, 2019 - Neuroscientists reveal that simple brain region can guide complex feats of mental activity
February 20, 2019 - Study finds new link between food allergies and multiple sclerosis
February 20, 2019 - First gene therapy operation for macular degeneration is a success
February 20, 2019 - Physicians graduated outside the U.S. offer better care for Medicare patients with complex needs
February 20, 2019 - Study shows therapeutic potential of VEGF-A mRNA for regenerative angiogenesis in humans
February 20, 2019 - FDA Approves Keytruda (pembrolizumab) for the Adjuvant Treatment of Patients with Melanoma with Involvement of Lymph Node(s) Following Complete Resection
February 20, 2019 - Study identifies brain cells that modulate behavioral response to threats
February 20, 2019 - Researchers take closer look at how viruses bind cells and cause infection
February 20, 2019 - Newly developed gene therapy helps decelerate aging process
February 20, 2019 - Study suggests new treatment strategy for deadly brain cancer
February 20, 2019 - Scientists develop unique hybrid implant that imitates bone structure
February 20, 2019 - Push-ups can be tailored to meet specific needs of individuals
February 20, 2019 - Early-career job loss has long term health implications
February 20, 2019 - CVD Does Not Modify Depression-Mortality Link in Elderly
February 20, 2019 - Electrical activity early in fruit flies’ brain development could shed light on how neurons wire the brain
February 20, 2019 - Machine learning technique helps predict which asthma patients respond to corticosteroid therapy
February 20, 2019 - Self-reported sleep duration is a useful tool to measure sleep in children, study suggests
February 20, 2019 - T-cells play key role in how the body fights follicular lymphoma
February 20, 2019 - Study shows how 3D organization of genetic material helps perpetuate the species
February 20, 2019 - Researchers engineer stem cell with ‘suicide genes’ to induce cell death in all but beta cells
February 20, 2019 - Study reveals major sex differences in management of cardiovascular risk factors among U.S. adults
February 20, 2019 - Health Tip: Get Your Child to School on Time
February 20, 2019 - Shortcut strategy for screening compounds with clinical potentials for drug development
February 20, 2019 - Common acid reflux drugs tied to elevated risk for kidney disease
February 20, 2019 - Microbiome could be culprit when good drugs do harm
February 20, 2019 - Prenatal exposure to forest fires causes stunted growth in children
February 20, 2019 - Gene therapy restores hearing in mice with congenital genetic deafness
February 20, 2019 - First molecular test predicts treatment response for kidney cancer
February 20, 2019 - New method for improved visualization of single-cell RNA- sequencing data
February 20, 2019 - Researchers capture altered brain activity patterns of Parkinson’s in mice
February 20, 2019 - A possible blood test for detecting Alzheimer’s disease before symptoms show
February 20, 2019 - Primary care physicians associated with longevity, new research finds
February 19, 2019 - New study identifies many key lessons to establish sanctioned safe consumption sites
February 19, 2019 - Single CRISPR treatment can safely and stably correct genetic disease
February 19, 2019 - Multinational initiative to study familial primary distal renal tubular acidosis
February 19, 2019 - Breakthrough study highlights the promise of cell therapies for muscular dystrophy
February 19, 2019 - Subsymptom Threshold Exercise Speeds Concussion Recovery
February 19, 2019 - Midline venous catheters – infants: MedlinePlus Medical Encyclopedia
February 19, 2019 - Searching for side effects
February 19, 2019 - Humanity is all right, probably, although human extinction remains quite possible, researcher says
February 19, 2019 - Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows
February 19, 2019 - Anti-cancer immunotherapy could be used to fight HIV
February 19, 2019 - Customized Micropatterning for Improved Physiological Relevance
February 19, 2019 - Unique gene therapy approach paves new way to tackle rare, inherited diseases
February 19, 2019 - Activating gene that helps excite neurons reverses depression in male mice
February 19, 2019 - Science Puzzling Out Differences in Gut Bacteria Around the World
February 19, 2019 - Cells that destroy the intestine
February 19, 2019 - On recovery, vulnerability and ritual: An exhibit in white
February 19, 2019 - Scientific Duo Gets Back To Basics To Make Childbirth Safer
Studies provide insight into molecular changes prior to onset of arthritis

Studies provide insight into molecular changes prior to onset of arthritis

image_pdfDownload PDFimage_print

The results of two studies presented today at the Annual European Congress of Rheumatology (EULAR 2018) provide insight into molecular changes prior to the onset of arthritis which could inform future novel diagnostics and early therapeutic interventions.

Rheumatoid arthritis (RA) is characterised by joint inflammation leading to destruction of bone and cartilage. Since structural joint damage is irreversible, early recognition and treatment is a key focus in an effort to halt the progression of the disease. There is a phase before any evidence of RA where specific autoantibodies are present in the body. Individuals who have these antibodies are referred to as RA-risk, however only a subset of these will develop active disease in the short term.

“These studies may help us better understand and potentially identify which individuals classified as at-risk will go on to develop RA,” said Professor Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. “This is important because it will contribute to the development of early preventative strategies including potential pharmacological treatment to prevent the onset of disease.”

Study reveals synovial tissue gene signatures associated with development of disease in RA-risk individuals.

Samples of synovial tissue were taken from the knee joint of 67 RA-risk individuals who were then followed to see if they went on to develop RA. An explorative genome-wide transcriptional profile study was carried out in 13 individuals to identify gene transcripts with a significant association with arthritis development. These ‘gene signatures’ were then validated using quantitative real-time PCR† to measure changes in specific genes.

“Our results clearly show molecular changes appearing in the synovial tissue before the onset of arthritis,” said Dr. Lisa van Baarsen, Principal Investigator at the Amsterdam Rheumatology and Immunology Center | Academic Medical Center, the Netherlands. “The characterisation of these gene signatures will enable us to better understand the pathophysiology of the pre-clinical phase of the disease and potentially identify novel drug targets for preventive intervention.”

An explorative genome-wide transcriptional profiling study in 13 individuals demonstrated that an increased expression of 3,151 transcripts was associated with a higher risk of arthritis development, and 2,437 transcripts with a lower risk. Further analysis revealed that individuals who developed RA had a higher expression of genes involved in several immune response-related pathways (e.g. T-cell and B-cell receptor pathways, cytokine and chemokine signalling and antigen processing and presentation) and lower expression of genes involved in extracellular matrix receptor interaction, Wnt-mediated signal transduction and lipid metabolism.

Investigators chose 27 differentially expressed genes for validation in the whole study cohort using quantitative real-time PCR. This analysis classified the RA-risk individuals into two groups, where most individuals who developed RA were grouped together (p=0.03).

Immunohistochemistry analyses (n=54) of the samples taken at inclusion showed that most individuals already had an abundant expression of chemokine CXCL12 and its receptor CXCR4 which are known to accumulate in the synovium of rheumatoid arthritis patients. They also showed that RA-risk individuals that developed arthritis were more likely to show a positive gp38 staining and lower lipid staining.

BCR clones predict imminent onset of rheumatoid arthritis in at-risk patients.

Another cohort study in 129 RA-risk individuals validated recent findings that dominant B-cell receptor (BCR) clones in peripheral blood, can accurately predict imminent onset of arthritis in RA-risk individuals.

“Our data support a new biomarker that demonstrates better predictive power compared with other available biomarkers evaluated so far,” said Ms. Anne Musters, MD, Amsterdam Rheumatology and Immunology Center | Academic Medical Center, the Netherlands. “We think that peripheral BCR clones can be used to identify RA-risk individuals that will go on to develop arthritis, which will support the evaluation of early interventions to prevent the onset of disease.”

Results of the study showed that the number of dominant BCR clones was significantly increased in RA-risk individuals who developed arthritis within three years (p<0.0001). The optimal cut-off for the test was calculated at five or more dominant BCR clones and applying this test to the study cohort resulted in 45 BCR positive and 84 BCR negative individuals. Over the complete 104 months follow up period, only 13% of BCR-clone negative individuals developed RA compared to 76% of the BCR-clone positive individuals. This resulted in a relative risk of 5.8 (95% CI 3.2-10.3, p<0.0001).

By subdividing the individuals further, it was demonstrated that the number of dominant BCR clones significantly correlated with the risk of developing arthritis. Having 10 or more dominant BCR clones corresponded with a positive predictive value of 94% within three years. Within this period none of the 84 BCR negative individuals developed arthritis, indicating that, based on such test results, these individuals may be reassured concerning imminent RA risk.

Source:

https://www.eular.org/sysModules/obxContent/files/www.eular.2015/1_42291DEB-50E5-49AE-5726D0FAAA83A7D4/04_abstract_op0204_and_op0266_detecting_ra_early_3_0.pdf

Tagged with:

About author

Related Articles