From the Guidelines
IgG subclass deficiencies primarily manifest as recurrent respiratory infections, particularly sinusitis, bronchitis, and pneumonia, with increased susceptibility to encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae, as noted in the practice parameter for the diagnosis and management of primary immunodeficiency 1. The severity of symptoms varies widely, with some individuals remaining asymptomatic while others suffer from chronic or recurrent infections.
- IgG2 deficiency specifically correlates with infections by encapsulated organisms,
- while IgG3 deficiency is associated with respiratory infections and allergic disease,
- and patients may also develop bronchiectasis, chronic sinusitis, and autoimmune disorders over time. Some patients with IgG subclass deficiencies exhibit impaired specific antibody production, with impaired polysaccharide responses commonly observed among young patients with IgG2 subclass deficiency 1. Gastrointestinal infections, allergies, and asthma can be more common in these patients. Management typically involves prompt treatment of infections with appropriate antibiotics, and in cases of recurrent severe infections, immunoglobulin replacement therapy may be necessary (typically 400-600 mg/kg every 3-4 weeks), as outlined in the principles of management of IGGSD 1. Prophylactic antibiotics might be used in some cases. The underlying mechanism involves impaired humoral immunity, as IgG subclasses have specialized functions in pathogen neutralization, complement activation, and opsonization, with each subclass (IgG1, IgG2, IgG3, and IgG4) having distinct roles in immune protection. It is essential to consider the clinical implications of IgG subclass deficiencies in the context of the severity of infections, autoimmunity, and other manifestations of abnormal immunity and of the progression of symptoms over time, as noted in the practice parameter for the diagnosis and management of primary immunodeficiency 1.
From the Research
Clinical Manifestations of IgG Subclass Deficiencies
The clinical manifestations of Immunoglobulin G (IgG) subclass deficiencies can vary from asymptomatic to recurrent infections resistant to prophylactic antibiotics 2. Some common clinical manifestations include:
- Recurrent, mainly respiratory infections 3, 4
- Atopic disorders and autoimmune diseases as comorbidities 2
- Impaired vaccine response and an increased risk of malignancy, particularly in patients with no allergic comorbidities and those with non-common variable immunodeficiency (CVID) humoral immunodeficiency, IgM deficiency, IgG2 deficiency, and CD4 lymphopenia 2
- Lung dysfunction and viral diseases in patients with decreased IgG3 levels 5
IgG Subclass Deficiency-Associated Infections
Patients with IgG subclass deficiencies are prone to infections due to encapsulated microorganisms such as:
- H influenzae 5
- Pneumococci 5 These infections can be recurrent and may require prophylactic antibiotic therapy or intravenous immunoglobulin treatment 3, 5
Diagnostic Considerations
The diagnosis of IgG subclass deficiencies can be challenging, as total IgG serum levels may be normal or even increased 5. Therefore, it is essential to quantify the IgG subclasses and assess the clinical relevance of the deficiency 6. Patients with severe recurrent infections and IgG subclass deficiency may benefit from intravenous immunoglobulin treatment 5