Pathogenesis of Autoimmune Disease

Question 1

Define Rheumatoid Arthritis.

Answer 1

Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis of synovial joints

Question 2

What is the site of inflammation in rheumatoid arthritis?

Answer 2

Synovium

Question 3

What are the two main autoantibodies that are associated with rheumatoid arthritis?

Answer 3

Rheumatoid factor

Anti-cyclic citrullinated peptide antibody

Question 4

Other than at joints, where else is synovium found?

Answer 4

Around tendons (tenosynovium)

Question 5

Define Ankylosing Spondylitis.

Answer 5

Chronic spinal inflammation that can result in fusion and deformity

Question 6

What is the site of inflammation in ankylosing spondylitis?

Answer 6

Entheses – where a ligament or a tendon inserts into bone

Question 7

What family of diseases is ankylosing spondylitis a part of?

Answer 7

Seronegative spondyloarthropathies

Question 8

Define Systemic Lupus Erythematosus (SLE).

Answer 8

Chronic tissue inflammation in the presence of antibodies directed at self-antigens
NOTE: it is inflammation of sterile tissue

Question 9

Lupus causes multi-site inflammation but state some sites that are particularly badly affected.

Answer 9

Joints, Skin and Kidneys

Question 10

What are the two autoantibodies that are associated with lupus?

Answer 10

Anti-nuclear antibodies

Anti-double stranded DNA antibodies

Question 11

What family of diseases is lupus a part of?

Answer 11

Connective tissue diseases

Question 12

On which chromosome is HLA encoded?

Answer 12

Chromosome 6

Question 13

A change in which class of MHC is associated with rheumatoid arthritis, ankylosing spondylitis and SLE?

Answer 13

Ankylosing spondylitis = Class 1

Rheumatoid Arthritis + SLE = Class 2

Question 14

Which cells express class I MHC and which cells recognise this class of MHC?

Answer 14

All nucleated cells (they display endogenous antigens)

They are recognised by CD8+ T cells

Question 15

Which cells express class II MHC and which cells recognise this class of MHC?

Answer 15

Antigen presenting cells e.g. macrophages, dendritic cells (they display exogenous antigens)
Recognised by CD4+ T cells

Question 16

How does HLA-B27 cause ankylosing spondylitis?

Answer 16

Ankylosing spondylitis is independent of CD8+ T cells
HLA-B27 has a propensity to misfold, which causes cellular stress and triggers the release of IL-23 and IL-17 by adaptive immune cells and innate immune cells
The release of chemical mediators leads to inflammation
The cellular stress is most likely to occur in innate immune cells and these are present in the entheses – hence why ankylosing spondylitis causes enthesitis

Question 17

What is the difference in the specificity of the autoantibodies in SLE?

Answer 17

Anti-nuclear antibodies are found in all cases of SLE but isn’t specific to SLE
Anti-dsDNA antibodies are specific to SLE – serum level of this antibody correlates with disease activity

Question 18

How is the presence of anti-nuclear antibodies detected?

Answer 18

Some cells are permeabilised so the antibodies can enter the cell andthen the patient’s serum is washed over the cells
If there are anti-nuclear antibodies, they will bind to the nuclearantigens

Question 19

What are the features of a sick lupus patient in terms of complement levels and serum levels of anti-dsDNA antibodies?

Answer 19

Low complement levels

High serum levels of anti-dsDNA antibodies

Question 20

Blockage of which cytokine with biological therapy has proven to be very effective in reducing some of the negative effects of rheumatoid arthritis?

Answer 20

TNF-alpha- blocks lymphocyte recruitment and angiogenesis

Question 21

Other than cytokine blockade, what else can be targeted to improve symptoms in rheumatoid arthritis?

Answer 21

B cell depletion (B cell hyperactivity is a key feature of SLE)

Question 22

Name a monoclonal antibody that targets RANKL.

Answer 22

Denusomab

Question 23

State two drugs that deplete B cells and specify what they target.

Answer 23

Rituximab – anti-CD20 monoclonal antibody

Belimumab – anti-BLYS monoclonal antibody (BLYS is a B cell survival factor)

Question 24

MHC association of rheumatoid arthritis

Answer 24

HLA-DR4

Question 25

MHC association of ankylosing spondylitis

Answer 25

HLA-B27

Question 26

MHC association of systemic lupus erythematosus

Answer 26

HLA-DR3

Question 27

Importance of NSAIDS in SLE treatment

Answer 27

Interfere with arachidonic acid metabolism so reduce inflammation and pain from prostaglandins

Question 28

What are seronegative spondlyoarthropathies

Answer 28

Diseases with no autoantibodies