Pneumococcal Serotype-Specific Antibody Testing

PATHCHAT Edition No. 62
October/November 2019
Please contact your local Ampath pathologist for more information.

Authors:

• Dr. Cathy van Rooyen (Pathologist, Immunology)
• Dr. Sylvia van den Berg (Clinical Pathologist, Immunology)

Introduction

✅ What is Pneumococcal Serotype-Specific Antibody Testing?

• Used to assess humoral immune function in patients with suspected immunodeficiency.
• Helps diagnose functional antibody deficiencies that impact the ability to fight infections.
• Aids in evaluating response to pneumococcal vaccination.

📌 This test is essential for identifying primary and secondary immunodeficiencies.

Who Should Be Tested?

✅ Patients with Suspected Humoral Immunodeficiency:

• Recurrent infections, especially involving encapsulated bacteria:
  • Streptococcus pneumoniae.
  • Haemophilus influenzae.
  • Moraxella catarrhalis.
• Unexplained autoimmune cytopaenias (e.g., thrombocytopaenia, anaemia).
• Chronic infections, including persistent Giardia lamblia, Staphylococcus aureus, or Mycoplasma species.
• Malignancies associated with immune dysfunction.

✅ Specific Immunodeficiency Conditions:

• X-linked agammaglobulinaemia (severe hypogammaglobulinaemia).
• Common variable immunodeficiency (CVID).
• IgA deficiency.
• IgG subclass deficiency.
• Specific antibody deficiency (SAD).
• Primary T-cell defects with secondary antibody dysfunction.

📌 A delayed or inadequate response to vaccines can indicate underlying immune dysfunction.

Key Indicators for Immunodeficiency

✅ The SPUR Criteria for Infection Susceptibility:

• Severe infections requiring hospitalization.
• Persistent infections that do not resolve with standard treatment.
• Unusual infections caused by opportunistic or rare pathogens.
• Recurrent infections affecting the same organ systems (e.g., sinopulmonary infections).

📌 If a patient meets SPUR criteria, an immunological evaluation should be conducted.

Evaluation of Vaccine Response in Suspected Immunodeficiency

✅ Testing Vaccine Response:

• All patients with suspected humoral immune deficiency should have vaccine responses assessed if total IgG >1 g/L.
• Evaluation should be performed before starting immunoglobulin replacement therapy.
• Antibody levels must be monitored longitudinally to assess sustained immunity.

✅ Types of Vaccine Responses Measured:

1. Tetanus toxoid IgG (T-cell dependent response).
2. Streptococcus pneumoniae polysaccharide IgG (T-cell independent response).
3. Measles, mumps, rubella, varicella, and hepatitis B antibodies (assess previous exposure or vaccination).

📌 A patient with CVID may make protective tetanus antibodies but still require immunoglobulin replacement therapy due to poor responses to bacterial infections.

Pneumococcal Serotype-Specific Antibody Testing at Ampath

✅ Why Serotype-Specific Testing?

• Previous testing measured total pneumococcal IgG, which lacked sensitivity.
• New testing identifies responses to individual pneumococcal serotypes.

✅ Methodology:

• Luminex multiplex bead immunoassay (validated at Ampath).
• Measures IgG antibodies to 13 pneumococcal serotypes (included in Prevenar® vaccine).

✅ Serotypes Measured:

• 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F.

📌 This advanced testing improves accuracy in diagnosing humoral immune deficiencies.

Interpretation of Pneumococcal Vaccine Responses

✅ Response is Categorized into Four Phenotypes:

✔ Severe Deficiency:

• ≤2 protective titres (≥1.3 µg/mL) in patients over 6 years old.
• ≤2 protective titres (≥1.3 µg/mL) in children under 6 years old.

✔ Moderate Deficiency:

• <70% of serotypes protective in patients over 6 years old.
• <50% of serotypes protective in children under 6 years old.

✔ Mild Deficiency:

• Failure to generate protective titres to multiple serotypes.
• Failure of a twofold increase in ≥70% of serotypes.

✔ Memory Deficiency:

• Initial adequate response followed by loss of response within six months.

📌 A pneumococcal serotype-specific antibody level ≥1.3 µg/mL is considered protective.

Recommended Vaccination Strategy Based on Age

✅ Children Under 2 Years:

• Hexaxim® (DTPa-hepB-IPV-Hib) + Prevenar®.

✅ Children 2–6 Years:

• Tetraxim® (DTacP-IPV) + Pneumovax 23®.

✅ Individuals Over 6 Years:

• Adacel Quadra® (dTacP-IPV) + Pneumovax 23®.

📌 Pneumovax 23® is required to assess post-vaccination pneumococcal antibody response in patients over 2 years.

Recommended Testing Strategy at Ampath

✅ Testing Panel Includes:

1. Baseline pre-vaccination S. pneumoniae serotype-specific IgG levels.
2. Four-week post-vaccination levels.
3. Six-month post-vaccination levels to assess waning immunity.

✅ Additional Supporting Tests:

• Tetanus toxoid IgG antibodies.
• Total IgA, IgM, IgG levels (with or without IgG subclasses).
• Memory B-cell panel (supports diagnosis of CVID or IgG subclass deficiency).
• Lymphocyte subsets (if a T-cell defect is suspected).

📌 This comprehensive assessment provides a clearer picture of humoral immune function and the need for immunoglobulin therapy.

Summary of Pneumococcal Serotype-Specific Antibody Testing

✅ Indications:

• Diagnosis of functional humoral immunodeficiencies (primary or secondary).

✅ Interpretation of Results:

• Comparison of pre-vaccination, 4-week, and 6-month post-vaccination antibody levels.
• Inadequate responses indicate potential immunodeficiency.

✅ Accompanying Tests:

• Tetanus toxoid IgG, total IgG, IgA, IgM.
• Memory B-cell analysis, lymphocyte subsets.

✅ Specimen Collection:

• 1 SST tube (clotted sample).

✅ Test Mnemonics:

• PNEUMOPRE (Baseline pneumococcal serotype-specific IgG).
• PNEUMOPOST (4-week & 6-month post-vaccination levels).

📌 This test is crucial in diagnosing humoral immune deficiencies and guiding treatment decisions.