Lecture 14 The Science of Rheumatoid Arthritis

Question 1

What is the synovium

Answer 1

Thin membrane that covers the inner surface of the joint

Question 2

How many layers does the synovium have

Answer 2

2

Question 3

What 2 cells does the synovium contain

Answer 3

Fibroblast and macrophages

Question 4

Name 4 functions of the synovium

Answer 4

Maintenance of intact tissue surface
Lubrication of cartilage
Control of synovial fluid volume and composition
Nutrition of chondrocytes within joints

Question 5

Autoantibodies that occur in RA recognise _______ and ______

Answer 5

Type II collagen

Systemic antigens

Question 6

In seropositive rheumatoid arthritis can rheumatoid factor be detected

Answer 6

Yes

Question 7

In seronegative rheumatoid arthritis can rheumatoid factor be detected

Answer 7

No

Question 8

What genes play a key role in susceptibility to RA and disease severity

Answer 8

HLA-DRB1
HLA-DR4
Polymorphism- PTPN22, CTLA4, c-REL

Question 9

Name environmental factors linked to RA

Answer 9

Can be:
o	Viruses (EBV, CMV)
o	E. Coli
o	Mycoplasma
o	Periodontal disease (Porphyromonas gingivalis)
o	Microbiome (gut microbes)
Smoking

Question 10

Describe the ACPA response in RA

Answer 10

Citrullination: conversion of amino acid arginine in a protein into the amino acid citrulline.

Enzymes called peptidylarginine deiminases (PADs) replace the primary ketimine group by a ketone group

Question 11

What is synovitis in RA

Answer 11

Inflammation of synovial

Characterised by hyperplasia

Question 12

What cells infiltrate the intimal lining of the synovium?

Answer 12

Mononuclear cells: CD4+ T cells, macrophages and B cells
• Neoangiogenesis is induced by local hypoxic conditions and cytokines
• Insufficient lymphangiogenesis limits cellular egress
• Neutrophils are present in synovial fluid

Question 13

What are the functions of inflammatory cytokines

Answer 13

Induce expression of endothelial-cell adhesion molecules
Activate synovial fibroblasts, chondrocytes, osteoclasts
Promotes angiogenesis
Activate leukocytes
Promote auto-Ab production

Question 14

What causes cartilage and bone destruction

Answer 14

Proteases

Osteoclasts that are activated under the influence of RANKL produced by RA synovium

Question 15

Systemic consequences of RA

Answer 15

Vasculitis
Nodules
Scleritis
Amyloidosis
CV Disease
Fatigue and reduced cognitive function
Liver- elevated acute-phase response, anaemia of chronic disease
Lungs- interstitial lung disease, fibrosis
Muscles- sarcopenia
Bone-osteoporosis