Science of Rheumatoid Arthritis Flashcards
What is RA
Rheumatoid arthritis is a chronic symmetric polyarticular inflammatory joint disease, which primarily affects the small joints of the hands and feet
Is RA common?
Rheumatoid Arthritis is one of the commonest, severe, chronic conditions of adulthood with potentially progressive, disabling arthritis and a range of systemic effects
What are the layers of the synovium
Intimal lining
Sub-intimal
What is contained in the intimal lining
- Thin 2 or 3 layers of cells
- Two cell types (fibroblast and macrophages)
What is contained in the sub intimal lining
- Connective tissue containing blood vessesl, fibroblasts and macrophages
Whats the function of the synovium
Maintenance of intact tissue surface
Lubrication of cartilage
Control of synovial fluid volume and composition (hyaluronan, lubricin)
nutrition of chondrocytes within joints
What antibodies are commonly associated with RA
Autoantibodies, such as Rheumatoid Factor and anti-citrullinated protein antibodies, are commonly associated with RA
What groups are people with RA split into
Seronegative rheumatoid arthritis
Seropositive rheumatoid arthritis
What is Seropositive rheumatoid arthritis
Patients have - Rheumatoid factor
and/or
Anti-citrullinated protein antibody (ACPA) – less favourable prognosis
What is Seronegative rheumatoid arthritis
Autoantibodies are not detectable
What are environmental triggers that causes RA
Smoking and bronchial stress
Infectious agents
What infectious agents can cause RA (x5)
- Viruses (EBV, CMV)
- E. Coli
- Mycoplasma
- Periodontal disease (Porphyromonas gingivalis)
- Microbiome (gut microbes)
What are the genetics of RA
Genetic contribution to RA estimated to be ~50-60%
Overall incidence of RA ~1% rises to 2-4% in siblings and 12-15% in monozygotic twins
What can happen when a genetically susceptible individual has repeated insults of an environmental trigger
Formation of immune complexes and rheumatoid factor
and/or
Altered citrullination of proteins and breakdown of tolerance, with resulting ACPA response
What % of patients is RF found
70%
What do RF autoantibodies target
They target the Fc portion of Gg antibodies
What is an Fc portion on an antibody
All antibodies have an Fc antibody. It is were immune cells bind to the antibody.
What happens when the Fc portion of the antibody has been targeted
The bodies immune system cant recognise the antibody and attacks it.
What does the Anti-citrullinate protein antibody target
Targets citrullinated proteins such as fibrin and fillagrin
What is a citrullinated protein
Citruliinated proteins are proteins that have arignated AA converted to citrullinate (making it seem foreign)
What antibody is more sensitive and specific to RA
Anti-citrullinate protein antibody
What is the pathological hallmark of RA
Synovitis
What cells are found in an inflamed synovium due to RA
Macrophages Cytokines Fibroblast like Synoviocytes (type A) T-cells Plasma cells
What cells are found in an inflamed synovial fluid due to RA
Neutrophils
immune complexes
What do macrophages do to cause RA in the synovium
Make cytokines (TNF-a, IL-1 and IL-6) which cause inflammation
What do the cytokines secreted by macrophages do to cause RA in the synovium
Stimulate FLS which activate and proliferate
They also stimulate rankl expression which act with the cytokines to activate osteoclasts which then cause bone erosion
What do fibroblast like synoviocytes do to cause RA in the synovium
Stimulate rankl expression which act with the cytokines to activate osteoclasts which then cause bone erosion
Also secrete proteases which cause the cartilage to break down (cartilage degredation).
What can fibroblast like synoviocytes do which gives a typical feature of RA
When FLS are activated they can migrate from joint to joint (one hand to the other) – WHY IS SYMETTRICAL
How does the cartilage respond to its breakdown via FLS
The cartilage also secretes proteases creating a positive feedback loop of degradation
What do T cells do to cause RA in the synovium
They promote inflammation
- They secrete interleukin 17 which promotes macrophage activity and also stimulate the FLS
They also help in expression in RANKL (bone erosion
What do plasma cells do to cause RA in the synovium
They assist in inflammation through cytokines and antibodies
What do neutrophils do to cause RA in the synovium
Contain proteases and reactive oxygen species which cause bone and collagen degradation (inflammation)
What do immune complexes do to cause RA in the synovium
These are complexes which bind to each other and promote inflammation
What causes increased angiogenesis at the synovium in RA
The cytokines produces by the cells increases vascular permeability and expression of adhesion molecules in the vasulature allowing the immune cells to migrate into the joints
