Head of Laboratory: Vyacheslav Adarichev
° search for and development of new blood-based biomarkers for rheumatoid arthritis;
° motility and activation of synoviocytes of arthritic pannus;
° autoimmune mechanisms of Brucellosis-induced spondyloarthropathy
Autoimmune Arthritis, Inflammation and Pannus
Rheumatoid arthritis is a progressive chronic inflammatory disease of autoimmune etiology; the disease affects approximately 1% of human population worldwide. In rheumatoid arthritis, synovial joints are invaded with activated fibroblast-like synoviocytes (RA-FLS), cells that build up a specific inflammatory and invasive tissue called pannus, a primary source of cartilage- and bone-degrading enzymes. RA-FLS behave like a local invasive solid tumor, even capable of spreading the disease to as yet unaffected joints. The invasive properties of RA-FLS as well as activated FLS from murine arthritis models directly correlate with the rate of joint destruction and deformities, and poor disease outcome. Progressive synovial inflammation, if not properly treated, eventually results in severe damage of joints, deformities and serious health problems.
Finding serum biomarkers that closely correlate with pannus activity is an attractive way to monitor the disease and detect early effects of the prescribed therapeutic treatment. We also address the mechanisms of the enhanced aggressiveness and motility of RA-FLS, study the mechanisms of the pannus formation in order to provide better understanding etiology and control of autoimmune arthritis.
Infections and Autoimmunity
Spondyloarthropathy (or spondyloarthritis) is a group of diseases that share similar clinical features of asymmetric inflammation of joints (oligoarthritis), inflammation of sacroiliac joints (sacroiliitis) and axial skeleton, inflammation of the sites where tendons or ligaments insert into the bone (enthesitis). Spondyloarthritides comprise ankylosing spondylitis, psoriatic arthritis, enteropathic spondyloarthritis associated with inflammatory bowel diseases, and reactive arthritis. The most prevalent among spondyloarthritides is ankylosing spondylitis that occurs in 0.1-1.4% depending on the population studied.
The role of infections in etiology of spondyloarthritides has long been debated. Evidence of preceding genitourinary or gastrointestinal infections (e.g., Chlamydia, Salmonella, Shigella, Yersinia, Campylobacter, Klebsiella) is found in the majority of reactive arthritis cases. Spondyloarthritis is genetically linked to the major histocompatibility complex HLA-B27 alleles. Class I molecules, as HLA-B27, normally present intracellular antigens for immune system.
Several hypotheses have been proposed to explain this mysterious genetic association.