3. Autoimmunity

Question 1

what drives autoimmune diseases?

Answer 1

Presence of auto antibodies or auto reactive T cells resulting in organ fibrosis

Question 2

What factors influence the development of autoimmune diseases?

Answer 2

Genetic factors
Environmental factors
Hormonal factors - female after puberty
Infectious microbe exposure

Question 3

Why do some infections trigger autoimmune diseases?

Answer 3

Some microbes have a similar epitope to one present within the body - mimicry

Question 4

What is autoimmunity?

Answer 4

Immune response against the host due to the break in immunological tolerance for self-antigen(s).

Question 5

What is an autoimmune disease?

Answer 5

Disease caused by tissue damage or disturbed physiological responses due to an auto-immune response

Question 6

What 2 groups can autoimmune diseases be split into?

Answer 6

Organ specific

Non-organ specific

Question 7

What is the difference between organ and non-organ specific autoimmune diseases?

Answer 7

Organ specific : auto antigen only present in one organ resulting in organ/tissue specific damage

Non-organ specific : autoantigen found in multiple sites resulting in damage throughout the body. Usually type III hypersensitivity

Question 8

What investigation results would confirm presence of an autoimmune disease?

Answer 8

Serology or biopsy showing the presence of auto reactive T cells / auto antibodies at a level of which correlates with disease severity and activity

Question 9

What are the most common autoimmune diseases in the UK?

Answer 9

Systemic lupus erythematosus

Sjögren’s syndrome

Question 10

What autoimmune diseases have primary autoantibodies driving the disease?

Answer 10

Graves’ disease (anti-TSHR)
Myasthenia gravis (anti-acetylcholine receptor )
Lambert-Eaton myasthenia syndrome (anti-voltage-gated Ca2+ channel)
Goodpastures syndrome (anti-anti-glomerular basement membrane)

Question 11

What autoimmune diseases are driven by secondary autoantibodies?

Answer 11

SLE  (anti-nuclear)
Pernicious anaemia (anti-gastric parietal cell)
Hashimoto thyroiditis (anti-thyroid peroxidase)
Rheumatoid arthritis (anti-rheumatoid factor)

Question 12

Why might babies of mothers with autoimmune diseases experience symptoms?

Answer 12

Autoimmune disease can be transferred to neonates as maternal autoantibodies can be transferred but this effect diminishes by 6 months when maternal IgE/IgG fades.

Question 13

What are the treatment options for autoimmune diseases?

Answer 13

Plasma exchange to remove auto antibodies (plasmapheresis)
Immunosuppressive drugs to suppress auto reactive T cells
Anti-inflammatory drugs (corticosteroids) to treat the tissue damage
Replacement therapy surgery to treat organ dysfunction

Question 14

What causes autoimmune rheumatic diseases?

Answer 14

Result from a break in immune tolerance by producing pathogenic antibodies which result in a heterogenous group of diseases which affect multiple systems.

Question 15

How is autoimmune rheumatic disease diagnosed?

Answer 15

Investigations showing presence of autoantibodies
Clinical features
Patient history

Question 16

On clinical examination, how will a patient with autoimmune rheumatic disease present?

Answer 16

Ulcers
Muscle weakness
Alopecia
Rash

Question 17

What investigations should be done in a patient with suspected autoimmune rheumatic disease?

Answer 17

Clinical examination
FBC
Urea
Electrolytes
Creatinine
Liver enzymes
CRP
Plasma viscosity 
ESR  
Antibodies

Question 18

What are the risk factors for SLE?

Answer 18

Female
Afro-Caribbean
South Asian

Question 19

What is the treatment for SLE?

Answer 19

Lifestyles modifications
DMARDs (disease-modifying antirheumatic drugs)
Steroids
IV cyclophosphamide (in severe cases)

Question 20

What are the risk factors of rheumatoid arthritis?

Answer 20

Female

CVS disease

Question 21

What is used in the diagnosis of rheumatoid arthritis?

Answer 21

S factor diagnosis - stiffness, swelling, squeezing

Question 22

How is rheumatoid arthritis treated?

Answer 22

DMARDs
Steroids
Biological ( in severe cases)

Question 23

Name some organ specific auto immune diseases

Answer 23

Hashimoto’s thyroiditis (Thyroid peroxidase and thyroglobulin)
Type 1 diabetes mellitus (Pancreatic islet cells)
Multiple sclerosis (Myelin sheath)
Goodpasture’s disease (Glomerular/alveolar basement membrane) Addison’s disease (Steroid-21 hydroxylase - adrenal cortex)
Graves’ disease (Thyroid-stimulating hormone receptor)
Myasthenia gravis (Acetylcholine receptor)
Pernicious anaemia (Intrinsic factor - terminal ileum)

Question 24

Name some non-organ specific autoimmune diseases

Answer 24

Autoimmune haemolytic anaemia (RBC antigens)
Rheumatoid arthritis (rheumatoid factor - Fc portion of IgG)
SLE - (dsDNA + histones)
Sjogren’s syndrome (nuclear antigens)

Question 25

What autoimmune diseases are caused by a type IV hypersensitivity reaction? What common presentation do they share?

Answer 25

``` Type 4 causes destruction of the tissue resulting in a loss of function Hashimoto’s thyroiditis T1DM Multiple sclerosis Goodpastures disease Addison’s disease ``` RA Sjögren’s syndrome

Question 26

What autoimmune diseases can be cause by a type II hypersensitivity reaction?

Answer 26

Graves’ disease Myasthenia gravis Pernicious anaemia Autoimmune haemolytic anaemia

Question 27

What type of hypersensitivity reaction occurs in systemic lupus erythematosus?

Answer 27

Type III

Question 28

How does autoimmunity develop to autoimmune disease?

Answer 28

1. Presence of autoantibodies/autoreactive T cells 2. Levels of autoantibodies correlate with disease severity and activity 3. Autoantibodies/autoreactive T cells found at the site of tissue damage

Question 29

What is meant by sensitivity?

Answer 29

The % of individuals with a condition that the test identifies

Question 30

What is meant by specificity?

Answer 30

The % of individuals who do not have condition that the test excludes

Question 31

What techniques can be used in detecting autoimmune diseases?

Answer 31

``` Infiltration of T cells into specific tissue Indirect immunofluorescence Immunofluorescence Radioimmunoassay Coombs test (ANA) Agglutination (RA) ```

Question 32

What diseases can be induced in the neonate due to autoimmune disease in pregnancy?

Answer 32

``` Thrombocytopenia Haemolytic anaemia Neonatal Graves’ disease Neonatal myasthenia gravis Neonatal SLE ```

Question 33

What is the edrophonium test?

Answer 33

Patient is given a IV anti cholinesterase drug. This inactivated the enzyme cholinesterase that breaks down acetylcholine. If there is an improvement in the patients symptoms the most likely diagnosis would be myasthenia gravis.

Question 34

What environmental factors trigger autoimmunity?

Answer 34

Hormones Infections Drugs

Question 35

What is the next promising therapeutic alternative for autoimmune diseases?

Answer 35

Monoclonal antibodies

Question 36

Why is it important to test for autoantibodies in autoimmune rheumatic diseases?

Answer 36

- aid diagnosis - associated with specific clinical features - disease prognosis - to stratify therapy

Question 37

What symptoms do we look out for when taking a history for autoimmune rheumatoid arthritis?

Answer 37

- Current symptoms (Pain/Morning Stiffness/ Swelling/ Pattern of joint involvement - small joints) - Evolution (Acute or chronic/ Associated events /Response to treatment/Family history) - Involvement of other systems (Skin, eye, lung/ Malaise, weight loss, fevers, night sweats) - Impact on patient's lifestyle - Constitutional symptoms (Fever, fatigue, weight loss, night sweats, Poor appetite) - “Glove and sweater” approach

Question 38

What does the glove and sweater approach mean when taking a history for autoimmune rheumatoid disease?

Answer 38

Gloves = raynauds, joint pains and swelling(synovitis), hand rash Sweater = proximal muscle weakness > myalgia, hair loss, eye and mouth dryness, nose bleeds, mouth ulcers, pleuritic chest pain, pericardial pain, truncal rash/photosensitivity, limb weakness

Question 39

What is the lupus mneumonic?

Answer 39

A rash points medical diagnosis ``` ANA positive Renal abnormalities Arthralgia/arthritis Serositis Haematological abnormalities Photosensitivity Oral ulcers Immunological abnormalities Neurological abnormalities Malar rash Discoid rash ```