LOCO2

Question 1

o Seropositive ACPA RA patients have which HLA [1]

Answer 1

HLA DR4B1

Question 2

Name three genes linked to RA [3]

Answer 2

 HLA DR4
 PTPN22 gene
 TRAF5 gene

Question 3

What type of disease is linked to RA? [1]

Answer 3

o Periodontal disease
 E.g synovial fluid of RA has found to have oral anaerobic antibodies

Question 4

Name 3 infective agents linked to triggering RA [3]

Answer 4

 EBV
 Rubella
 Mycoplasma organisms

Question 5

Which joint being affected by RA is a sign of later onset RA? [1]

Answer 5

o Shoulder involvement a sign of later onset RA

Question 6

o For classification purposes, patients are said to have RA if they satisfy at least 4 of which 7 criteria? [7]

Answer 6

 Morning stiffness: lasting ≥1 hour before maximal improvement.

 Arthritis of three or more joint areas: simultaneously have had soft tissue swelling or fluid, observed by a physician

 Arthritis of hands:
at least one swollen area in a wrist, MCP, or PIP.

 Serum RF

 Symmetrical arthritis

 Radiographic changes

 Rheumatoid nodules

Question 7

Which hand joints are commonly involved in RA? [3]

Answer 7

wrist, MCP, or PIP

Question 8

What is the name for PIP deformity? [1]

Answer 8

o Boutonniere’s deformity

Question 9

Explain MoA of conventional synthetic DMARDs? [4]

Answer 9

Question 10

Which drug class for RA are linked with risk of infection like TB? [1]

Answer 10

TNF-alpha inhibitors

Question 11

Name 3 TNF-alpha inhibitors used to treat RA [3]

Answer 11

 Etanercept
* Binds to TNF-a

 Infliximab
* Monoclonal antibody
* Binds to transmembrane and soluble forms of TNF-a

 Adalimubab

Question 12

 Anakinra MoA? [1]

Answer 12

o IL-1 blocker

Question 13

 Rituximab MoA?

Answer 13

• Anti CD20

Question 14

RA treatment

o T cell co-stimulation blocker? [1]

Answer 14

 Abatacept

Question 15

Name 3 Janus kinase-1 selective inhibitors

Answer 15

All end in ibib

• Tofactibib
• Baricitinib
• Upadacitinib

Question 16

Name 3 Janus kinase-1 selective inhibitors

Answer 16

All end in ibib

• Tofactibib
• Baricitinib
• Upadacitinib

Question 17

1 What is the mechanism of action of infliximab?
1 mark

Answer 17

Blocks actions of TNFalpha

Question 18

2 What class of drug does Naproxen belong to and what is its mode of action and explain why it is given as a gastro-intestinal preparation?

Answer 18

Nonsteroidal anti-inflammatory drug (1/2 mark) It inhibits competitively cyclooxygenase 1 and 2 converting **arachidonic acid to prostaglandins **(COX1 and 2) (1 mark)

Prostaglandins are essential for production of bicarbonate and mucus that protects the stomach from the acid secretion. (1 mark) So the inhibition of Cox1 in the stomach will mean there is less mucous and less bicarbonate so more damage (1/2 mark)

Question 19

3 What is the name of the overgrowth of the synovium in RA and explain how this affects the joint.
(3 marks)

Answer 19

Pannus (1/2 mark)

It grows over and into the articular cartilage (1/2 mark), it produces cytokines that attack the cartilage and break it down, (1 mark) plus the cytokines also induce synovial fibroblasts to differentiate as osteoclasts that break down the peri-articular bone. (1 mark)

Question 20

4 Bella is seropositive for ACPAs? Briefly explain how NETosis is thought to be linked to the formation of these ACPAs

Answer 20

Neutrophils release extracellular traps and as part of this process release protein arginine deiminase 4 (1 mark) which will citrullinate peptides (1 mark). These are taken up by antigen presenting cells to T cells that activate plasma cells to produce the anti-citrullinated peptide antibodies (1 mark)  

Question 21

Explain why ulnar drift and subluxations occur in RA [2]

Answer 21

The ulnar drift and subluxations are due to the flexor muscles being larger and stronger than the
extensors so there is more likely to be flexor contractions