RA Workshop DAT

Question 1

Foetal exposure to maternal MHC gene composition has what effect?

Answer 1

Can promote RA development.

Question 2

What are 4 prognostic factors of RA development?

Answer 2

1. Erosions at baseline (on X-ray)
2. High CRP
3. Functional impairment (HAQ)
4. Presence of RF or anti-CCP antibody

Question 3

Why is the presence/absence of antibodies to citrullinated protein antigen a prognostic factor for RA?

Answer 3

Change of amino acid arginine to citrulline triggers antigen presence and release, T and B cell.

Question 4

Extreme fatigues in RA are thought to be the result of what?

Answer 4

Levels of pro-inflammatory interleukin 1 and 6 and their effects on brain endothelial cells.

Question 5

What are the 9 effects of TNFa release?

Answer 5

1. Proinflammatory cytokine release: IL-1, Il-6, IL-23 and GM-CSF.
2. Hepcidin induction
3. PGE2 production
4. Osteoclast activation - bone resorption.
5. Chondrocyte activation: metalloproteinase production, cartilage destruction.
6. Angiogenesis
7. Leukocyte accumulation: induction/maintenance of HLA class II expression.
8. Endothelial cell activation: upregulation of E-selectin and V-CAM1. Leukocyte accumulation.
9. Chemokine release: RANTES, MCP-1, Il-8, SDF-1. Leukocyte accumulation.

Question 6

What are the effects of TNFa induced Hepcidin induction?

Answer 6

Hepcidin is a protein that in humans is encoded by the HAMP gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.

In states in which the hepcidin level is abnormally high such as inflammation, serum iron falls due to iron trapping within macrophages and liver cells and decreased gut iron absorption. This typically leads to anemia due to an inadequate amount of serum iron being available for developing red cells. When the hepcidin level is abnormally low such as in hemochromatosis, iron overload occurs due to decreased ferroportin mediated iron efflux.

Question 7

TNFa stimulated chondrocyte activation causes what?

Answer 7

Metalloproteinase production

cartilage destruction.

Question 8

TNFa stimulated endothelial cell activation causes what?

Answer 8

Upregulation of E-selectin and VCAM-1.

Luekocyte accumulation.

Question 9

TNFa causes the release of what pro-inflammatory cytokines?

Answer 9

IL-1
IL-6
IL-23
GM-CSF

Question 10

Chemokines such as___________ are released upon TNFa presence.

Answer 10

RANTES
MCP-1
IL-8
SDF-1