What is the management and treatment of Immunoglobulin G2 (IgG2) deficiency?

Management and Treatment of Immunoglobulin G2 (IgG2) Deficiency

The management of IgG2 deficiency should focus on treating allergy if present, using prophylactic antibiotics, and cautiously considering immunoglobulin replacement therapy only in selected patients with recurrent infections that impact quality of life and mortality risk. 1

Diagnosis Confirmation

Before initiating treatment, proper diagnosis must be established:

• Diagnosis requires at least two measurements of IgG subclass levels at least one month apart showing consistently low IgG2 levels 1
• Normal total IgG with low IgG2 subclass levels (below 5th percentile) suggests IgG2 subclass deficiency 1
• Low IgG2 levels in children may be transient and resolve within months to years, so follow-up testing is essential 2
• Assessment of functional antibody responses to polysaccharide antigens is critical, as impaired responses are commonly seen with IgG2 deficiency 1

Clinical Manifestations

• Recurrent respiratory tract infections (particularly with encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae) are the most common presentation 1, 3
• Severity of infections correlates with degree of IgG2 deficiency 4
• IgG2 deficiency may occur in isolation or in combination with other immunoglobulin deficiencies 3, 4
• Post-hematopoietic stem cell transplantation patients with IgG2 deficiency are at increased risk for bacterial pneumonia 5, 6

Treatment Algorithm

First-Line Management:

1. Treatment of underlying allergies if present 1

   • Allergic conditions often coexist with IgG2 deficiency and may exacerbate respiratory symptoms

2. Prophylactic antibiotics 1

   • Consider for patients with recurrent respiratory infections
   • Target coverage for encapsulated bacteria

3. Pneumococcal vaccination 1

   • Patients with IgG2 deficiency, especially those with impaired polysaccharide responses, may benefit from conjugate pneumococcal vaccines
   • Some patients with IgG2 deficiency require two doses of conjugate vaccine when one dose is typically sufficient 1

Second-Line Management:

1. Immunoglobulin replacement therapy 1, 3
   • Should be considered cautiously and only in selected patients
   • Indicated when:
     • Patient has recurrent infections that negatively impact quality of life 1
     • Aggressive antibiotic therapy and prophylaxis have failed 1
     • Patient has intolerable side effects or hypersensitivity to antibiotics 1
   • Typical dosing: 0.3-0.4 g/kg body weight every 3-4 weeks 3

Monitoring and Follow-up

• Monitor frequency and severity of infections 1
• Reassess IgG2 levels periodically, as levels may normalize over time, especially in children 2
• Evaluate response to pneumococcal vaccination using serotype-specific antibody measurements 1
• Consider functional antibody testing (opsonophagocytic assay) when available 1

Special Considerations

• Children: Low IgG2 levels in early childhood may resolve completely within several months to years 2
• Post-transplant patients: IgG2 deficiency after hematopoietic stem cell transplantation increases susceptibility to bacterial pneumonia and may require immunoglobulin replacement 5, 6
• Rituximab therapy: Patients receiving rituximab are at higher risk for decreased IgG2 levels 6

Common Pitfalls to Avoid

• Overdiagnosis: A one-time low IgG2 level is insufficient for diagnosis; confirmation with repeat testing is essential 1
• Overtreatment: Not all patients with IgG2 deficiency require immunoglobulin replacement therapy 1
• Inadequate functional assessment: Measuring only IgG2 levels without assessing antibody responses to vaccines may lead to inappropriate treatment decisions 1
• Ignoring clinical context: Treatment decisions should be based on infection history and severity, not solely on laboratory values 1