Primary Immune Deficiency
Primary phagocyte deficiencies
- Chronic granulomatous disease
- Leukocyte adhesion deficiencies
- Defects in cytokines and cytokine receptors
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Complement pathway deficiencies
- Classical, alternative, and lectin pathways
- Lytic phase
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Primary antibody deficiencies: Impaired development- Impaired function
- X-linked agammaglobulinemia
- Selective IgA deficiency
- Common variable immune deficiency (CVID)
- Specific antibody deficiency
Hyper-IgM syndrome |
Primary T-lymphocyte deficiencies: Impaired development, survival, migration, function:
- DiGeorge syndrome
- Bare lymphocyte syndromes
- Severe combined immune deficiency
Hyper-IgE syndrome (autosomal dominant)
Wiskott-Aldrich syndrome
Ataxia-telangiectasia |
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| Primary antibody deficiencies: |
X-linked agammaglobulinemia
- males are affected
- present with severe bacterial infections during infancy.
- Investigation:
- reduction in B-cell numbers (B cell maturation failure in bone marrow)
- immunoglobulin levels: low or undetectable.
- immunoglobulin replacement therapy and
- antibiotics to treat infections.
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Selective IgA deficiency
- Most common primary antibody deficiency
- Usually asymptomatic
- About 30% of individuals experience recurrent mild respiratory and gastrointestinal infections.
- Investigation:
- serum IgA levels: low or undetectable
- serum IgG levels: compensatory increase in some patients
- Specific treatment is generally not required.
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Common variable immune deficiency (CVID)
- characterized by low serum IgG levels and failure to make antibody responses to exogenous pathogens.
- It is a heterogeneous adult-onset primary immune deficiency.
- The presentation is with recurrent infections, and bronchiectasis is a recognised complication.
- Paradoxically, antibody-mediated autoimmune diseases, such as idiopathic thrombocytopenic purpura and autoimmune haemolytic anaemia, are common in CVID.
- It is also associated with an increased risk of malignancy, particularly lymphoproliferative disease.
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Specific antibody deficiency
- defective antibody responses to polysaccharide antigens. ***
- Some patients are also deficient in the antibody subclasses IgG2 and IgG4
- There is overlap between specific antibody deficiency, IgA deficiency and CVID, and some patients may progress to a more global antibody deficiency over time.
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Investigations (as a whole)
- Serum immunoglobulins: IgM, IgG, IgA, IgE
- serum and urine protein electrophoresis: to exclude 2ndary causes of hypogammaglobulinemia
- Flow Cytometry (immunophenotyping): for B- and T-lymphocyte subsets
- Test immunization: to see specific antibody responses
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Management (as a whole)
- immunoglobulin replacement therapy: intravenously or subcutaneously.
- aggressive treatment of infections, prophylactic antibiotics may be indicated.
- Treatment may be self-administered and is life-long.
- immunization: live vaccines should be avoided.
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Complement pathway deficiencies
Clinical features
- Recurrent infection with encapsulated bacteria, particularly Neisseria spp.
- Genetic deficiencies of the classical complement pathway (C1, C2 and C4) → increased risk of autoimmune disease, particularly SLE.
- Mannose-binding lectin deficiency → increased incidence of bacterial infections
- Deficiency of the regulatory protein Cl inhibitor → recurrent angioedema.
Investigations
- CH50 (classical haemolytic pathway 50) and
- AP50 (alternative pathway 50) tests.
If abnormal, haemolytic tests are followed by
- Measurement of individual complement components.
Management
- vaccinated with meningococcal, pneumococcal and H. influenzae B vaccines
- Lifelong prophylactic penicillin to prevent meningococcal infection
- early access to acute medical assessment in the event of infection.
- Patients should also carry a MedicAlert or similar.
- Family screening for complement deficiencies with functional complement assays.
- The management of C1 esterase deficiency
