Immunology of Autoimmune Disease

Question 1

What is a monogenic disorder?

Answer 1

A single gene defects causing autoimmune disease

Question 2

Are monogenic disorders common?

Answer 2

No

Question 3

Give an example of a monogenic disorder

Answer 3

IPEX syndrome

Question 4

What is the presentation of IPEX syndrome?

Answer 4

• Before 6 months of age
• Type 1 diabetes
• Severe malabsorption syndrome
• Eczema
• Severe infections

Question 5

What is the pathogenesis of IPEX syndrome?

Answer 5

Mutation in FOXp3 gene which is essential for the development of regulatory T cells

Question 6

How many variants of each HLA molecule does an individual possess?

Answer 6

2

Question 7

What is the allele associated with Ankylosing Spondylitis?

Answer 7

HLA-B27

Question 8

What is the allele associated with Goodpasture’s Syndrome?

Answer 8

HLA DR2

Question 9

What is the allele associated with Graves Disease?

Answer 9

HLA DR3

Question 10

What is the allele associated with Systemic Lupus Erythematous?

Answer 10

HLA DR3

Question 11

What is the allele associated with Type 1 diabetes?

Answer 11

HLA DR3/4

Question 12

What is the allele associated with RA?

Answer 12

HLA DR4

Question 13

At what age and in who does autoimmune disease tend to affect?

Answer 13

In females around puberty

Question 14

What factors contribute to autoimmune disease?

Answer 14

Genes, immune regulation, environment

Question 15

What are the classifications of autoimmune disease?

Answer 15

Pathological: Gel and Coombs
Clinical: organ specific or non organ specific

Question 16

In Gel and Coombs classification, what types are involved?

Answer 16

II, III, IV

Question 17

What is an immune complex?

Answer 17

Autoantibody + circulating antigen

Question 18

Name a type III Autoimmune disease

Answer 18

SLE

Question 19

What is the pathophysiology of SLE?

Answer 19

• Antibodies produced against contents of cell nuclei
• Form immune complexes
• Deposited in small vessels in skin, joints, kidneys
• Complement activation
• Recruitment of other cells
• Inflammation

Question 20

What autoimmune diseases are associated with ANA?

Answer 20

SLE, scleroderma, Sjogren’s, dermatomyositis/polymyositis, mixed connective tissue disease, autoimmune hepatic disease

Question 21

What % of normal individuals can have a titre of ANA> 1:80

Answer 21

5%

Question 22

What is Speckled antibody associated with?

Answer 22

SLE and Sjorgrens

-Associated with anti-Ro, anti-LA

Question 23

What are Anti-centromere antibodies specific to?

Answer 23

Limited scleroderma

Question 24

What are Nucleolar ANA antibodies specific to?

Answer 24

Scleroderma

Question 25

What is Anti-Jo antibody associated with?

Answer 25

Polymyositis/Dermatomyositis

Question 26

What is Anti-La associated with?

Answer 26

Sjogren's Syndrome

Question 27

What is anti-RNP associated with?

Answer 27

Mixed connective tissue disease and SLE

Question 28

What is Anti-Ro antibody associated with?

Answer 28

SLE, maternal anti-Ro associated with Neonatal Lupus and congenital heart block

Question 29

What is Anti-Sm antibody associated with?

Answer 29

very specific for SLE

Question 30

What is Anti-Scl 70 associated with?

Answer 30

Diffuse scleroderma

Question 31

What is Anti-DNA binding protein associated with?

Answer 31

Highly specific for SLE

Question 32

What does a high titre of Anti-DNA antibody indicate?

Answer 32

High level of disease activity in SLE

Question 33

What does a low complement measure indicate in SLE?

Answer 33

High disease activity as complement is consumed when it is activated

Question 34

Give an example of a Type IV autoimmune disease

Answer 34

RA

Question 35

What is the immunopathogenesis of RA?

Answer 35

- Infiltration of synovium by activated CD4 cells - Chronic production of inflammatory cytokines in synovium - Recruitment of phagocytes - Recruitment of activated B cells which produce immunoglobulin - TNF and IL-1 are potent stimulators of fibroblasts, osteoclasts, chondrocytes, stimulate release of MMP - Additional synovium produced - Breakdown of bone and increased vascular formation - MMP destroys bone and cartilage

Question 36

What is the histology of synovial fluid in RA?

Answer 36

Intimal lining is hyperplastic

Question 37

What % of patients with RA are tested +ve for Rheumatoid Factor at the time of diagnosis?

Answer 37

50%

Question 38

After 2 years of having RA, what further % of patients will become seropositive for RF?

Answer 38

25%

Question 39

What % of patients will never have Rheumatoid Factor in RA?

Answer 39

25%