Immunodeficiencies

Question 1

CVID

Answer 1

= Common Variable Immunodeficiency

Most common primary immunodeficiency in adult requiring treatment
Type of B cell deficiency

10% familial

Two peaks: 1-5 years old and 18-25 years old
Clinical:
- recurrent sinopulmonary infections
- GIT
- skin infections
- autoimmunity
- neoplasia
- lymphoproliferation
- allergic disease
- bronchiectasis, resp faiure

Inv:

• low IgG
• hypogamma on eletrophoresis
• impaired vaccination response

Mx:

• IV gammaglobulin
• Abx
• avoid live vaccines

Question 2

X-linked agammaglobulinaemia

Answer 2

= XLA = Bruton’s

Similar to CVID, but early onset (6 months), no B cells, no lymphoid tissue
Type of B cell deficiency

Absence/mutation of Btk (Bruton’s tyrosine kinase)
Coded by Btk gene

Inv:

• hypogamma on electrophoresis
• undetectable Ig
• B cell count 0
• no plasma cels or germinal centres in tissue Bx

Treat as per CVID

Question 3

IgA deficiency

Answer 3

Absence of IgA +/- IgG subclasses
Dysregulation in Ig isotype class switching during B cell activation
Type of B cell deficiency

Cause: sporadic, familial, dru-induced (phenytoin, penicillamine), intrauterine infection

Inv:

• normal electrophoresis
• absent IgA
• normal B cell count

Mx:

• prompt Abx
• NOT IVIg
• if require transfusion, require blood form IgA-deficient donor or triple wash cells

Question 4

IgG subclass deficiency

Answer 4

Four IgG subclasses (IgG1-4) with different functions, deficiency is controversial
Type of B cell deficiency

Any combination may be low, but normal range not consistent across labs

Clinical:
- recurrent sinopulmonary infection

Inv:

• electrophoresis normal
• IgG levels normal or borderline low
• IgG subclasses: deficiency in one or more
• B cell count normal

Mx:
- consider gamma globulin replacement if high frequency recurrent bacterial infections

Question 5

Specific Antibody Deficiency

Answer 5

= SAD = SpAD = FAD

Clinical:
- recurrent URTIs, often paediatric

Inv:

• Ig levels normal
• B cells present
• specific Ab to vaccination impaired

Mx:

• vaccination
• IVIg

Question 6

Hyper IgM syndrome

Answer 6

X-linked
CD40 ligand deficiency
Type 1 = deficient/mutated T cell CD40L
Type of B cell deficiency

Absent CD40-CD40L signal in Tcell-Bcell collaboration –> failure of B cell isotype switching and memory B cell generation

Onset 1-2 years old

Clinical:

• recurrent bacterial infections
• acute/chronic diarrhoea

Inv:

• low IgA, IgG, IgE
• normal or inc IgM
• normal circulating B cells
• flow cytometry for surface CD40L

Mx:

• IVIg
• Bactrim prophylaxis
• G-CSF
• ???bone marrow Tx

Question 7

IdiopathicCD4 lymphopenia (ICL)

Answer 7

Rare
Low CD4 count, HIV negative
Type of T cell deficiency

Clinical:
- “T-cell type” infections eg. oesophageal candidiasis, MAC infection, disseminated VZV, cryptococcal pneumonia/meningitis

Inv:

• at least one clinical condition indicating severe immunosuppression
• CD4 count <300 or 20% lymphocytes
• no secondary cause
• repeatedly HIV seronegative
• beware T cell lymphomas

Mx:

• nil specific
• consider Abx prophylaxis

Question 8

CMC

Answer 8

= Chronic Mucocutaneous Candidiasis

Chronic/recurrent candida infection
Type of T cell deficiency

Inv:
- lack Th17 cells

Question 9

SCID

Answer 9

= severe combined immunodeficiency

Paediatric
Failure to thrive, chronic diarrhoea
Recurrent opportunistic infections
Variable severity