16 Jun Synovial tissue profiling in autoantibody positive at risk individuals reveals gene signatures associated with later development of rheumatoid arthritis
MedicalResearch.com Interview with:
Dr. Lisa van Baarsen PhD
Principal Investigator at the Amsterdam Rheumatology and Immunology Cente
Academic Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The discovery that autoantibodies can be present years before the onset of clinical symptoms of rheumatoid arthritis (RA) enables us to study autoantibody positive individuals who are at risk of developing RA. In patients with established disease the target tissue of RA, the synovial joints, is characterized by cellular infiltration and inflammation. Moreover, successful therapy decreases this synovial inflammation. In the past, our department already showed (PMID: 21177292; PMID: 24574210) that in autoantibody positive at risk individuals there is no overt cellular infiltration present in the synovium.
In the current study we performed a so called discovery-based approach to investigate at a genome-wide gene expression level (using microarrays) whether the synovium is altered at a molecular level before onset of rheumatoid arthritis.
Our molecular and microscopic studies on synovial biopsies obtained from autoantibody positive individuals indeed revealed interesting differences between those at risk individuals who developed disease after follow up and those who did not.
MedicalResearch.com: What should readers take away from your report?
Response: Now we can identify individuals at risk of developing rheumatoid arthritis and with better predictive biomarkers within reach, preventive medicine for RA may be a realistic development. However we first need to delineate the best drug targets for this preclinical phase of disease. Our research study shows that already years before onset of clinical symptoms, the synovium is changing. This is important information, since this gives more insight into the pathogenesis of disease and may lead to the identification of new drug targets for preventive intervention.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Investigating the target tissue of a disease is highly important in order to understand disease pathogenesis. In addition, studying the essential centers where immune responses are initiated, the lymphoid organs, may also provide new leads on the key players in driving development of rheumatoid arthritis. Since we did not find an overt cellular infiltration yet in this preclinical phase of RA, our future research will be focused on studying the function of the resident stromal cells in synovium as well as in lymphoid organs.
Currently, D. Gerlag and P.P. Tak are employees of GlaxoSmithKline, UK. GlaxoSmithKline was not involved in this study.
JOURNAL: Annals of the Rheumatic Diseases
MEETING: EULAR 2018 – Annual European Congress of Rheumatology
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