Rheumatoid Arthritis Phathophysiology

Question 1

What is RA?

Answer 1

Chronic autoimmune disorder, progressive, systemic, inflammatory disorder effecting synovial joints.

Question 2

Where does RA effect commonly?

Answer 2

Hands, feet, knee hip.

Question 3

70% of RA express what?

Answer 3

Human Leukocyte Antigen (HLA-DR4)

Question 4

What is also associated with RA?

Answer 4

Antibodies anti-citrullinated peptide antibodies (ACPA) & Rheumatoid Factor (RF)

Question 5

What is the first stage of RA pathophysiology?

Answer 5

1 - Initiator stage:
Initiating event unkown.
APC, citrilliniation of proteins -> now seen as non-self.

Question 6

What is the second stage of RA pathophysiology?

Answer 6

2 - Inflammation phase :
Self antigen presented.
Clonal expansion of T &B cells.
Insufficient control by T reg cells.

Question 7

What is the third stage of RA pathophysiology?

Answer 7

3 - Self perpetuating phase :
Inflammatory dmg in synovium causes self-anigens ‘unseen’ by immune system to be seen
Causes immune resposne against cartilage.
Infiltration of immune cells.

Question 8

What is the fourth stage of RA pathophysiology?

Answer 8

4 - Destruction Phase :
Synovial fibroblasts & osteoclasts activated by cytokines (IL-6, TNF)
Destrution of bone &cartilage.

Question 9

What does B-cells do in RA?

Answer 9

Produce antibodies, which can activate complement system & also bind o activated macrophages in the synovium -> can cause inflammation.

Question 10

What does T-cells do in RA?

Answer 10

Activate monocytes, macrophages & synovial fibroblasts -> TNFa, IL-6 & IL-1

Question 11

What are the current therapies for RA?

Answer 11

Anti-inflammatory & immunosupresive drugs :
NSAIDS (COX-2)
DMARDs
Biologics