Primary Immunodeficiency

Question 1

What is immunodeficiency?

Answer 1

• malfunction of immune system
• inc. susceptibility to infections
• inc. risk of certain cancers
• inc. incidence of autoimmunity
• primary- congenital, genetic immunodeficiencies
• secondary- another disease, exposure to toxins immunodeficiencies

Question 2

What are features of primary immunodeficiency?

Answer 2

• part of immune system missing/functioning abnormally
• component of innate immunity
• stages of lymphocyte development
• response of mature lymphocytes to antigenic stimulation
• mainly caused by mutations
• can be caused by autoimmunity

* specific infections/tumour can indicate which part of the immune system is abnormal

Question 3

What types of infections/tumours can indicate problems with specific parts of the immune system?

Answer 3

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Question 4

What are the causes of primary immunodeficiency?

Answer 4

• mutations
• permanent alteration in DNA sequence of a gene
• can affect any part of immune system
• rare but can cause severe disease
• polymorphisms
• ≥ 1 variation of DNA sequence (usually single base pair)
• can affect any part of immune system
• moderate inc. risk of infection
• polygenic disorders
• > 1 gene causing disease
• mainly affect antibodies
• can be caused by autoimmunity

Question 5

What is severe combined immunodeficiency (SCID)?

Answer 5

• result of mutations
• group of disorders affecting both T + B cells
• severity varies on mutation + level of mutation
• can be autosomally inheritied or X-linked
• infants die within few months, unless treated immediately
• stem-cell treatment
• is screened

Question 6

What are examples of different polymorphism immunodeficiencies?

Answer 6

• Human Leukocyte Antigen (HLA)
• unable to bind viral peptides -> worse outcome
• Mannin-binding lectin (MBL)
• MBL binds to sugars in bacterial cell walls and activates compliment pathways
• polymorphism affects infection risk

Question 7

What are features of polygenic disorders?

Answer 7

• recurrent infections (pneumococcus or Haemophilus spp), but normal total IgG
• do not respond to polysaccharide antigens, poor level of pneumococcal antibodies after vaccination
• can be caused by autoimmunity

Question 8

What are features of common variable immunodefciency (CVI)?

Answer 8

• polygenic disorder
• IgA + specific antibody deficiency
• low levels of total IgG + IgM, number of B + T cells variable
• most common immunodeficiency (1 in 20,000)
• recurrent infections; respiratory tract (pneumococcus or Haemophilus spp.), gut, skin, nervous system
• autoimmunity common
• autosomal-recissive inheritance

Question 9

What are the investigations for primary immunodeficiencies?

Answer 9

• clinical presentations
• infections in first few weeks of life
• CVID in adulthood
• unusual/recurrent infections
• diarrhoea
• unusual rashes
• history
• family history of neonatal death
• family history of consanguinity
• lymphocyte count (flow cytometry)
• < 1 × 10⁹/L
• antibody levels
• dec. immunoglobulins
• dec. specific antibodies

Question 10

What is the treatment for primary immunodeficiency?

Answer 10

Mild:

• prophylactic antibiotics

Severe:

• immunoglobulin replacement therapy
• antibodies, Ig from donors

SCID:

• stem cell transplantation
• gene therapy
• avoid life vaccines
• prophylaxis