What is the clinical significance of Immunoglobulin G (IgG) subclass deficiency?

From the Guidelines

Immunoglobulin G subclass deficiency (IGGSD) should be considered in patients with recurrent infections, low IgG subclass levels, and normal total IgG, IgM, and IgA concentrations, and treatment may include immunoglobulin replacement therapy in selected cases with significant antibody deficiency 1.

Key Points

• IGGSD is a condition where one or more IgG subclasses are low, despite normal total IgG levels.
• Diagnosis of IGGSD is controversial and requires careful evaluation of IgG subclass levels, as well as assessment of clinical symptoms and immune function.
• Measurement of IgG subclasses can be useful in evaluating patients with recurrent infections, particularly if total immunoglobulin levels are normal.
• Treatment of IGGSD may include immunoglobulin replacement therapy, but this should be reserved for patients with significant antibody deficiency and recurrent infections.
• Other conditions, such as selective antibody deficiency and common variable immunodeficiency, should be considered in the differential diagnosis of IGGSD.

Evaluation and Management

• Evaluation of IGGSD should include measurement of IgG subclass levels, as well as assessment of clinical symptoms and immune function.
• Patients with IGGSD should be monitored for recurrent infections and other complications, such as autoimmune disorders.
• Immunoglobulin replacement therapy may be considered in patients with significant antibody deficiency and recurrent infections, but the decision to treat should be made on a case-by-case basis.
• Other treatments, such as antibiotics and anti-inflammatory medications, may also be necessary to manage symptoms and prevent complications.

Evidence-Based Recommendations

• The diagnosis and management of IGGSD should be guided by evidence-based recommendations, such as those outlined in the practice parameter for the diagnosis and management of primary immunodeficiency 1.
• Immunoglobulin replacement therapy should be reserved for patients with significant antibody deficiency and recurrent infections, as outlined in the guidelines for the use of immunoglobulin replacement therapy in patients with antibody deficiency diseases 1.
• Patients with IGGSD should be monitored regularly for recurrent infections and other complications, and treatment should be adjusted as needed to prevent long-term morbidity and mortality.

From the Research

Immunoglobulin G Subclass Deficiency

• Immunoglobulin G (IgG) subclass deficiency is a primary antibody deficiency characterized by recurrent respiratory tract infections and the inability to produce effective IgG responses 2.
• IgG subclass deficiencies can be associated with autoimmune disorders, and some patients may have decreased IgG3 levels, which can be linked to lung dysfunction and viral diseases 3.
• The clinical relevance of IgG subclass deficiencies is significant, as patients with these deficiencies may suffer from infections due to encapsulated microorganisms such as H influenzae and pneumococci 3.

Diagnosis and Treatment

• Diagnosis of IgG subclass deficiency can be challenging, and the decision to treat with immunoglobulin replacement therapy (IGRT) should be based on a practical approach, considering clinical, laboratory, and radiological assessments 4.
• IGRT is the mainstay of therapy for many patients with primary antibody deficiencies, and both subcutaneous and intravenous routes of administration can be effective and well-tolerated 5.
• Treatment regimens can be individualized to provide optimal medical and quality-of-life outcomes, and patient education is essential to understand the disease and the importance of continuous therapy 5.

IgG Subclass Distribution

• IgG subclasses have been recognized since the early 1960s, and four subclasses (IgG1, IgG2, IgG3, and IgG4) exist, with IgG1 being the most abundant (65-70% of total circulating IgG) 6.
• Deficiencies in the various IgG subclasses have been detected in adults and children with common variable hypogammaglobulinemia, as well as in those with relatively normal total IgG levels 6.
• The therapeutic implications of IgG subclass deficiency are still being determined, and further research is needed to understand the clinical significance of these deficiencies 3, 6.