Inborn Errors of Immunity

Question 1

What does the innate vs adaptive immune system detect? What are the receptors of the two divisions?

Answer 1

• Innate detects PAMPs, and DAMPs (WAT?)
• Adaptive detects a huge range of specific antigens
• Innate uses PRRs (WAT?)
• Adaptive uses TCRs and Ig on surface of B cells

Question 2

What are inborn errors of immunity (including the exact kind of change(s) that cause them)? What do they predispose to?

Answer 2

• IEI are genetically determined, inborn errors of immunity
• They can be widely heterogeneous, and can have variable clinical phenotype
• They predispose to recurrent/unusual infections, as well as increased risk of malignancy/immune regulation (interesting that these two link together)

Question 3

What are some possible warning signs of primary immunodeficiency?

Answer 3

• Need for IV antibiotics to clear infections
• Persistent thrush/fungal infection (what else causes thrush? why?)
• FHx
• Multiple serious sinus infections in one year

Question 4

Why is early and accurate diagnosis of inborn errors of immunity so important?

Answer 4

• Early intervention can prevent recurrent infections and irreversible end organ damage
• Early diagnosis allows for best possible planning of interventions and long-term plans, such as vaccination strategies
• Can also allow for genetic screening in other family members who may have inherited the disorder(s) moving forward

Question 5

What kinds of infections are more likely in someone with phagocyte/complement/humoral/cellular immunodeficiency?

Answer 5

• Phagocyte: bacteria/fungal
• Complement: bacteria
• Humoral: bacteria (+ some viruses)
• Cellular: all

Question 6

Outline three types of tests that can be used to diagnose inborn errors of immunity. Are these broadly similar for each patient as part of the immunodeficiency screen?

Answer 6

1. Genetic testing: DNA is extracted/sequenced from a sample of tissue, and assessed for abnormalities
2. Immunological assays: assess the number and function of cells, levels of Ig, cytokines etc.
3. Clinical: Hx (?recurrent infections, ?autoimmunity, ?Fhx, ?recurrent miscarriages)

Question 7

Outline the 4 broad categories of treatment for inborn errors of immunity

Answer 7

1. Preventitive (immunisation, screening, prophylactic Rx)
2. Supportive (IvIg, Plasmapheresis)
3. Targeted (enzyme replacement, immunosuppressive biologics)
4. Curative (stem cell transplant, thymus transplant)