Rheumatoid Arthritis Flashcards
How would you describe Rheumatoid arthritis?
- systemic inflammatory disease
- predilection for synovium of the diarthrodial joint (lined by fibrocartilage or hyaline cartilage, with synovial fluid)
- inflammatory arthritis that is usually BILATERAL, CHRONIC, affecting LARGE AND SMALL JOINTS
RA criteria (7)
1) morning joint stiffness for more than 1 hour
2) arthritis of 3+ joints at same time
3) arthritis of hand joints
4) symmetrical
5) rheumatoid nodules
6) Rheumatoid factor in serum
7) radiographic changes: erosions or bone demineralization adjacent to the arthritis
* patients fulfill criteria fi they have 4/7, and criteria 1-4 must be present for 6+ weeks*
epidemiology (3)
- F:M ~3:1
- rare in men under 45
- more common in 4th and 5th decades of life
Rheumatoid Arthritis Pathogenesis (4)
1) genetic : HLA and cytokine genes
2) envrionmental: bacterial and viral triggers, other factors like smoking
3) sex hormones (F:M 3:1)
4) Aging, may be associated with senescence of the immune system
What is Citrullination/deimination and how is it related to Rheumatoid Arthritis?
- conversion of arginine into citrulline (post-translational modification)
- arginine is charged, citrulline is uncharged –> affect protein folding
- anti-citrullinated protein (ACP) antibodies are highly specific for rheumatoid arthritis and about as sensitive as Rheumatoid factor for dianosis of RA
Citrullinated proteins in RA (6)
1) endolase
2) keratin
3) fibrinogen
4) fibronectin
5) collagen
6) vimentin
80% of RA patients improve clinically when they are pregnant. This is probably not a hormonal effect, but rather…..
A consequence of the immune switching that allows pregnancy to continue (Th1 to Th2)
In terms of pathology, RA is a prolifertive synovitis that is vascular and contains these 3 characteristics:
- mononuclear cell infiltrate (HLA-DR, APC’s / macrophages in close contact with TH1 cells)
- B cells and antibody secreting plasma cells in lymphoid follicle-like structures
3, evidence of “partial transformation” of the type B synovial cells i.e. malignant-like
-demonstrates by loss of contact inhibition, increased expression
of oncogenes, and anchorage independent growth.
Histologically, how does normal synovium compare to RA synovium?
Normal: nice, thin, one cell thick
RA: thickened prolifeative tissue, vasculature channels, outgrows vascular supply, very aggressive, ROS develop
What is pannus?
What does pannus invade?
What does this invasion cause? (3)
- Pannus: proliferatinve synovium
- Pannus invades articular cartilage and bone
- Results in: cartilage destruction, joint destruction, bony erosion
Which joint is usually not involved in RA?
Distal interphalangeal joint (DIP)
What characters are involved in bone destruction related RA?
RANKL! induced by activated T cells and IL18 (recall T cells are turned on in RA). RANKL enhances monocyte migration , prmoting the accumulation of osteoclasts in the synovium.
what is mostly mainly found in the fluid of rheumatoid synovium?
neutrophils***important to know
4 innate effector cells contained within the Rheumatoid Synovium:
1) macrophages (and cytokines TNF-a, IL1, 6, 12, 15, 18, 23)
2) Mast cells
3) NK cells
4) Neutrophils
4 important things to know about T cells in RA:
- predominant cell infiltrating the synovium
- produce IFNj (found in synovium)
- produce IL-17 (proinflammatory, activates osteoclasts and destroys cartilage)
- produces RANKL
