Immunodeficiency presenting as hypergammaglobulinaemia with IgG2 subclass deficiency

Area of Science:

• Pediatric Immunology
• Clinical Biochemistry

Background:

• Recurrent bacterial infections, lymphadenopathy, and failure to thrive are often investigated for causes other than immune deficiency when hypergammaglobulinaemia is present.
• Previous assumptions suggested that high immunoglobulin levels indicated a healthy immune system, potentially delaying diagnosis of specific deficiencies.

Purpose of the Study:

• To investigate the diagnostic utility of IgG subclass analysis in children presenting with features of immunodeficiency and concurrent hypergammaglobulinaemia.
• To challenge the conventional understanding that hypergammaglobulinaemia excludes primary immunodeficiency.

Main Methods:

• Case series of eight pediatric patients with recurrent infections and hypergammaglobulinaemia.
• Detailed immunological investigations including IgG subclass analysis and specific antibody production assessment.
• Treatment response evaluation following intravenous immunoglobulin (IVIG) administration.

Main Results:

• All eight patients exhibited low IgG2 levels and impaired specific antibody responses to common pathogens.
• Initial diagnoses considered included lymphoma, autoimmune disease, and chronic viral infection, highlighting diagnostic challenges.
• Symptomatic and clinical resolution was achieved in all patients after IVIG treatment.

Conclusions:

• Hypergammaglobulinaemia does not preclude the diagnosis of immunoglobulin and antibody deficiency, specifically IgG subclass deficiency.
• IgG subclass analysis is crucial in the immunological workup of children presenting with features of immunodeficiency and elevated IgG levels.
• This study underscores the importance of comprehensive immunological assessment beyond total immunoglobulin levels.