RA Flashcards
Epidemiology
Women:men= 3:1
1% worldwide population
Joint damage
Chronic inflammation of synovial joint
- Symmetrical
Presentation
Morning stiffness
Synovitis:
Swelling over extensor tendons, wrist and MCP joint
Synovium hyperplasia
Rheumatoid joint pathology
Pannus
- Thickened synovial membrane due to infiltration of cells
Synovial fluid thick with neutrophils
Bone erosion
Narrow joint space
Synovial tissue composition in RA
Ma
Macrophages and RA
Key effector cell for inflammation
Undergo
- Phagocytosis
- Antigen presentation
- Release of TNF, IL-1, IL-6
T cells and RA
Th17 and Th1 drive pathology
- Activated by APCs
Th17 produce IL-17
- Activate synovial fibroblast and osteoclast= breakdown of bone
Treg cells
- Lose suppressive effect even though they are upregulated
Blocking TNF
B cells and RA
Important for release of cytokines and antigen presentation.
Autoantibodies produced by B cells way before clinical presentation.
B cells diffuse into synovial
Anti-CD20 Ab to deplete B cells= beneficial
Neutrophils and RA
Undergo NETosis= drives inflammation
Cartilage erosion
Chondrocytes undergo apoptosis
Fibroblast adhere and invade cartilage
Bone erosion
IL-17, RANKligand, TNF, Il-6/1
= osteoclast differentiation and activation
Rheumatoid factor
Autoantibodies- against Fc portion of other antibody
- IgM/ IgG
Only present in 60-70% with RA
BUT:
- Not specific for RA
- Seronegative [no antibody in love]
Positve= disease worse
CCP Ab
or ACPA’
Only found in 60-80% but
Possibly pathogenesis
- Anti-CCP Ab immune complexes could activate inflammatory cells
-
Citrullination
Process of replacing arginine residue with citulline
- Could possibly trigger immune response
Genetic polymorphism of RA
HLA-DRB1 SE
- 30-50% overall risk
PTPN22
- T cell activation
CTLA4
- Suppresses T cell reaction
STAT4
TRAF1
