LG 3.3 Immunology of Joint Pain

Question 1

Spondyloarthritis has closest association than anything else to what molecule?

Answer 1

• HLA molecule

- It expresses HLA B27

Question 2

What are 4 pieces of evidence used to support the theory of RA being an autoimmune disease?

Answer 2

• Characteristic antibodies present: RF and ACPA.
• Auto-reactive T-cells (CD8+ particularly)
• There is an association with MHC genes and mutations in genes involved in T-cell activation and cytokine secretion.
• The response of the disease to immune modifying therapies.

Question 3

What are some causes that have to be present in order to break tolerance and initiate this immune reaction which leads to RA?

Answer 3

• Environmental, gene interactions, and infectious component.
• All must be present to break tolerance and initiate process.

Question 4

What are some environmental factors that can lead to tolerance break and RA?

Answer 4

• Female gender (hormones)
• Smoking and bronchial stress
• Infectious agents
• Urban setting
• Immune senescence (break down of immune system due to aging)

Question 5

What are some genetic factors that can lead to tolerance break and RA?

Answer 5

HLA molecules:
- DR4 subtypes of DRB1 alleles
- May bind pathogenic epitopes, containing citrulline
- Alter negative selection in thymus
PTPN22:
- protein tyrosine phosphatase Lyp
PADI4:
- enzyme converts arginine to citrulline