How RA Happens Flashcards
Citrullination
The post translational modification of arginine into citrulline
RA has been linked to anti-citrullinated protein/peptide antibodies
Possible environmental factors involved in RA
Cigarette smoking, tobacco
Gingivitis
Other bacterial or viral infections
Smoking effect on RA
Greatest known environmental risk factor for RA
Increases risk for developing ACPA in shared epitope-positive RA
Might lead to the production of ACPA in the lung
Might lead to activation of innate immunity in the lung
Rheumatoid factors
Autoantibodies to IgG, recognizing the epitopes on the Fc portion of the olecule
Present in the circulation of patients with RA for months to years prior to the onset of clinical disease
Combo of ACPAs and RF is a better predictor of subsequent RA than either alone
+ RF = worse prognosis
Synovitis in RA
Caused by influx and/or local activation of mononuclear cells and by angiogenesis
Synovial lining then becomes hyperplastic and it expands and forms villi
Synovial lining can invade CT and can result in bone erosion
Pannus
Osteoclast rich portion of the synovial membrane
Destroys bone
What is the most probable event that initiates the rheumatoid process?
The activation of T cells by as yet unknown antigens in the immunogenetically-susceptible host
4 consequences of T cell activation
Activation and proliferation of synovial lining and endothelial cells
Recruitment and activation of additional proinflammatory cells from the bone marrow and circulation
Secretion of cytokines and proteases by macrophages and fibroblast-like synovial cell
Autoantibody production
Angiogenesis in RA
Early pathologic response
Accompanied by the transudation of fluid, and the transmigration of both lymphocytes into the synovium and PMNs into the synovial fluid
Mass can get too great, causing ischemia
What is the principle cytokine that generates a proliferative synovitis
TNFa
