Ra Flashcards
What is rheumatoid arthritis (RA)?
A chronic inflammatory autoimmune disease characterized by pain, swelling, and progressive joint damage
RA affects 0.5–1% of the global population and is more common in women and developed countries.
What distinguishes RA from osteoarthritis?
RA can have an earlier onset and is associated with systemic complications
Osteoarthritis typically presents later in life.
What drives the pathology of RA?
Extreme inflammation of the synovial fluid driven by immune cell infiltration
This recruits osteoclasts, leading to bone breakdown and cartilage degradation.
What genetic factors increase the risk of RA?
Mutations in the MHC region, particularly HLA-DRB1, and non-MHC genes like CTLA4
Epigenetic changes also influence gene expression.
What immune cells are central to the inflammation in RA?
Neutrophils, macrophages, and CD4+ T-helper cells
B cells produce autoantibodies like RF and ACPAs, contributing to inflammation.
What role do inflammatory cytokines play in RA?
Key cytokines like TNF-α, IL-1, and IL-6 amplify inflammation and promote joint damage
These cytokines activate fibroblast-like synoviocytes (FLS) and other immune cells.
What are ACPAs and their significance in RA?
Anti-citrullinated protein antibodies that predict severe outcomes like bone erosion and cardiovascular disease
Approximately 80% of RA patients test positive for autoantibodies.
What enzymes are involved in the formation of autoantibodies in RA?
Peptidyl arginine deiminases (PADs)
PADs convert arginine into citrulline, leading to the generation of antibodies against citrullinated proteins.
What is the role of PADs in RA?
They trigger the immune system to produce antibodies against modified proteins
PAD2 and PAD4 are involved in histone citrullination and NETosis.
Which cellular signaling pathways are crucial in RA?
Notch, SYK, PI3K, JAK, Wnt, and MAPK
These pathways are involved in FLS activation and inflammatory responses.
What metabolic alterations are observed in FLS in RA?
Dysfunctional mitochondrial metabolism and reliance on the pentose phosphate pathway (PPP)
This affects cellular function and contributes to inflammation.
What are biological DMARDs (bDMARDs)?
Agents that target specific cytokines and immune pathways in RA treatment
Examples include TNF-α inhibitors, IL-6 receptor antagonists, and B-cell-depleting antibodies.
Name a common TNF-α inhibitor.
Adalimumab (Humira)
It is a fully human monoclonal antibody that binds to both soluble and transmembrane TNF-α.
What was the outcome of the PREMIER trial?
Combining adalimumab with methotrexate resulted in superior clinical outcomes compared to either treatment alone
49% of patients exhibited disease remission after 2 years.
What is the mechanism of action for etanercept?
It neutralizes TNF-α by preventing its binding to cellular receptors
Etanercept is a soluble dimeric fusion protein.
