The Science of Rheumatoid Arthritis Flashcards
Rheumatoid Arthritis Synovium
Thickened synovium due to marked hyperplasia of the synovial fibroblasts. Results in synovitis and destruction of the joints.
Functions of the synovium
Maintenance of intact tissue surface
Lubrication of Cartilage
Control of Synovial Fluid volume
Nutrition of chondrocytes within the joints
Definition of Rheumatoid Arthritis
Chronic Symmetric Polyarticular inflammatory joint disease which effects the small joints of the hands and the feet. This results from synovitis due to inflammatory cell infiltration characterised by synoviocyte proliferation and neoangiogenesis. The synovial fluid contains neutrophils which cause bone and cartilage destruction and therefore symptoms of the condition.
Autoimmunity of RA
Production of autoantibodies (Rheumatoid factors and anti-citrullinated protein). These recognise joint antigens (type 2 collagen and systemic antigens) contributing to inflammation (activation of complement)
Anti-CCP assays
Recognise citrullinated self proteins (alpha enolase, keratin, fibrinogen, fibronectin, collagen and vimentin), all of which have a less favourable prognosis.
Rheumatoid Factor
IgM is an autoantibody to self IgG Fc
Genetic Aetiology of Rheuamtoid Arthritis
HLA-DRB1, PTPN22, CTLA4, c-REL
Environmental Aetiology of Rheumatoid Arthritis
Smoking and bronchial stress can aggravate and are associated with the presence of the disease
Infectious agents - Viruses, ecoli, mycoplasma, periodontal disease, microbiome
Cirtullination
Conversion of the amino acid arginine in a protein to the amino acid citrulline
Development of Rheumatoid Arthritis
Altered post-transcriptional regulation resulting in self-protein cirtullination causing a loss of tolerance of dendritic cells, B cells and T cells. The secondary lymphoid tissue releases autoantibodies like ACPA and RF which results in the transition to arthritis.
Pathogenesis of RA
- Villous hyperplasia
- Infiltration of T cells and B cells and macrophages
- Intimal cell proliferation
- Production of cytokines and proteases
- Increased vascularity
- Self-amplifying process
T cells in RA
Low levels of T cell cytokines are present in RA synovium. There is a shift from homeostasis to inflammation (T cell cytokines are produced by Th1 and Th17 cells). The regulatory T cell function which suppresses activation of T cells is reduced. There is also T cell mediated B cell activation and direct cell-cell contact with macrophages.
B cells in RA
Synovial B cells are mainly localised in Tcell-Bcell aggregates (ectopic lymphoid follicles). CD20+ B cells are pathogenic.
Stromal Cell cytokines
Macrophages and Fibroblast Cytokines are abundant. Cytokine networks including TNF-alpha increase synovial inflammation. Chemokines that recruit inflammatory ce3lls into the joint are produced by macrophages and fibroblasts. Anti-inflammatory cytokines are produced at a level that is insufficient to off-set pro-inflammatory cytokines.
Inflammatory Cytokines
These induce expression of endothelial cell adhesion molecules. They activate fibroblasts, chondrocytes and osteoclasts. They promote angiogenesis and suppress T regulatory cells. They activate leukocytes and promote autoantibody production.
