The Science of Rheumatoid Arthritis

Question 1

What cell types are present in a normal synovium?

Answer 1

Macrophages and fibroblasts

Question 2

What changes occur in the synovium in rheumatoid arthritis?

Answer 2

The synovium expands and there is proliferation of the fibroblasts
The synovium becomes very thick and forms what is known as a pannus

Question 3

What are the characteristics of rheumatoid arthritis?

Answer 3

Rheumatoid arthritis is a chronic, symmetric, polyarticular, inflammatory joint disease that mainly affects the small joints of the hands and feet

Question 4

What are the characteristics of a pannus?

Answer 4

Pannus is characterised by the following:
Inflammatory cell infiltration
Synoviocyte proliferation
Neoangiogenesis

Question 5

What is present within the synovial fluid of affected joint cavities during flare ups of rheumatoid arthritis?

Answer 5

Neutrophils

Question 6

What are the complications associated with a pannus?

Answer 6

Can cause bone and cartilage destruction

Question 7

What autoantibodies are associated with rheumatoid arthritis?

Answer 7

Rheumatoid factor

Anti-citrullinated protein

Question 8

What genes can be associated with rheumatoid arthritis?

Answer 8

HLA-DRB1
PTPN22
CTLA4
c-REL

Question 9

What environmental factors can increase the risk of rheumatoid arthritis?

Answer 9

Smoking
Bronchial stress
Infectious agents

Question 10

Describe the mechanism of synovitis in rheumatoid arhritis

Answer 10

1. Lining proliferates, becomes active and aggressive
2. Macrophages in lining are activated
3. Lymphocytes can either diffusely infiltrate the sublining or form lymphoid aggregations
4. Sublining CD4+ cells display the memory cell phenotype
5. Synovial B cells and plasma cells exhibit evidence of antigen-driven maturation and antibody production
6. DCs can present antigens to T cells in synovial germinal layers
7. Neoangiogenesis is induced by local hypoxic conditions and cytokines
8. Insufficient lymphangiogenesis limits cellular egress
9. Neutrophils are present in the synovial fluid

Question 11

Describe the systemic consequences of rheumatoid arthritis

Answer 11

• Vasculitis, nodules, scleritis, amyloidosis = secondary to uncontrolled chronic inflammation
• Cardiovascular disease
– Altered lipid metabolism
– Elevated acute-phase reactants
– Increased endothelial activation
• Fatigue and reduced cognitive function (secondary fibromyalgia)
– Dysregulation of the HPA axis
• Liver
– Elevated acute-phase response
– Anaemia of chronic disease (IL-6 increases hepatocyte production of hepcidin, an iron-regulatory hormone)
• Lungs (interstitial lung disease, fibrosis)
• Muscles (sarcopoenia)
• Bone (osteoporosis)
Secondary Sjogren’s syndrome