B-cell deficiencies

Question 1

B-cell deficiencies can be…

Answer 1

• Failure of lymphocyte production (SCID)
• Failure of B-cell maturation (Bruton’s Hypergammaglobulinaemia)
• Failure of T-cell costimulation (Hyper IgM syndrome)
• Failure to secrete IgG (CVID, Selective antibody deficiency)
• Failure to secrete IgA (Selective IgA Deficiency)

Question 2

Bruton’s X-linked Hypogammaglobulinaemia

Answer 2

Pathophysiology

• Mutation in BTK gene (B-cell tyrosine kinase)
• Pre-B-cells cannot mature to form mature circulating B-cells

This results in:

• No circulating Ig after 3 months
• FTT
• Predisposed to bacterial and viral infections (Enterovirus) and parasitic/fungal infections

Investigations
- Protein electrophoresis shows no peak in the gamma window

Question 3

Hyper-IgM syndrome

Answer 3

Pathophysiology

• CD40L is not expressed on activated CD4+ T-cells, so they cannot help B-cells to undergo germinal centre reactions
• There is failure of isotype switching, so all B-cells express IgM
• There is some abnormality to T-cell function (because CD40L is not expressed)

Presentation

• Boys are affected after 3 months age (mostly XLR)
• FTT
• Recurrent bacterial infections
• PCP
• Autoimmune disease
• Malignancy

Immune phenotype:

• Normal T-cell count
• Normal B-cell count
• Raised IgM with undetectable IgA, IgG and IgE

Question 4

Common variable immunodeficiency (CVID)

Answer 4

• Failure of B-cells to differentiate into IgG-producting plasma cells
• Cause unknown

Presentation

• Can occur later in life
• Low IgG and IgA
• Poor/absent response to immunisation
• Absence of other defined immunodeficiency

Clinical features

• Recurrent, severe bacterial infections
• Pulmonary disease - bronchiectasis, persistent sinusitis,
• GI disease
• Granuloma formation
• Autoimmune disease
• Malignancy (Non-Hodgkin’s lymphoma)

Question 5

Selective IgA deficiency

Answer 5

• 1/600
• 2/3 asymptomatic
• 1/3 have respiratory tract infections

Question 6

Clinical features of B-cell deficiencies

Answer 6

• B-cells cover extracellular organisms
• Deficiency predisposes to these infections:
• – Bacterial
• – Toxins (Tetanus, Diphtheria)
• – Enterovirus

Question 7

Investigations for B-cell Deficiencies

Answer 7

• FBC, WBC and Differentials
• Lymphocyte subsets
• Serum Igs and protein electrophoresis

NB IgG is a marker of CD4+ T-cells

Functional tests of B-cell function:

• Specific antibody responses to known pathogens
• IgG antibodies against TETANUS, HIB, STREP PNEUMONIAE
• If levels are low, immunise (killed vaccines)and then repeat IgG measurements 6-8 weeks later

Question 8

Management of B-cell deficiencies

Answer 8

• Aggressive tx of infection
• Ig replacement (derived from pooled plasma of donors; life-ling treatment by IV or SC administration)
• HSCT not really useful