Immune Deficiencies 1b

Question 1

What are inborn errors of immunity?

Answer 1

Group of heterogenous conditions of immune dysfunction

Question 2

Clinical Features of IEI?

Answer 2

• increased susceptibility to infection
• auto-immune disease
• allergic disease
• auto-inflammatory disease
• viral related (EBV/HPV) cancer

Question 3

Variability in infection phenotype of IEI

Answer 3

1) Multiple episodes involving a wide range of infection (common organisms as well often rare opportunistic infections, live vaccines )
- Children&raquo_space; adults
-High or complete penetrance
- SCID, XLA, CGD

2) Susceptibility to weakly virulent organisms only:
-Environmental TB species and BCG vaccine
-Familial disease

3) Infections caused by single organism only:
-Invasive Neisseria disease and terminal complement pathway defects
-Herpes simplex encephalitis and type 1 interferon cortical neuronal defects

4) Some common infectious disease are caused by IEL
-TYK2 variants and TB
-Type 1 interferon/TLR7 deficiency and SARS-CoV-2 infection

Question 4

Link between infection susceptibility and autoimmunity?

Answer 4

Immune deficiency/LOF but less autoimmune diseases, strong immune system/GOF protects from diseases but may cause autoimmune conditions

Question 5

Inborn errors of immunity and Autoimmune diseases : common presentaiton

Answer 5

Pathological self reactive T cell immune response - usually present early.

e.g. ITP, SLE

Question 6

2 major categories of monogenic autoinflammatory disorders and causes?

Answer 6

1) IL1 inflammasomopathies - FMF
2. Type 1 IFNopathies ( AGS)

Question 7

Severly Ill COVID-19 patients had Ab that inhibited which responses?

Answer 7

Type 1 IFN

Question 8

Allergic conditions and IEI

Answer 8

AD STAT-3 LOF show increased susceptibility to infection with atopic conditions

Question 9

Early onset Cancer and IEI

Answer 9

EBV in immune deficiency patients causes Hodgkins, NHL, and smooth muscle cancer
- CD8 and NK cell deficiency and cytotoxic function/signalling/activation increases risk

Question 10

Presentation of IEI : what do infections look like?

Answer 10

Severe (sepsis, need for intravenous/OPAT antibiotics or fungal drugs)

Persistent
Multiple course of antibiotics to treat standard bacterial chest or sinus infection

Unusual infections
Opportunistic organism (Pneumocystis jirovecci, BCG)

Recurrent
More than 2 episodes of pneumonia within a year
More than 8 episodes of Otitis Media in a child

Consider possibility of IEL in conditions arising from complication of recurrent infections (Bronchiectasis and chronic rhino-sinusitis)

Question 11

What blood tests do to for IEI

Answer 11

FISH
F - FBC (including WBC differentials)
I - Immunoglobulins
S - Serum Complement
H - HIV Test

+ myeloma screen etc, and response to vaccine Abs