Children with recurrent infections: perspective of immunoglobulin G subclasses deficiency and impaired specific antibody responses

Children with recurrent infections present a diagnostic challenge due to the wide overlap between normal childhood infections and primary immunodeficiency diseases. Predominantly antibody deficiencies are the most common category of primary immunodeficiency disease in this population. While many predominantly antibody deficiency cases are identified through markedly low immunoglobulins levels or reduced B cell counts, some demonstrate subtler forms such as IgG subclass deficiency or specific antibody deficiency, which may present similar clinical symptoms but normal standard laboratory parameters. Diagnosing these conditions in children is particularly challenging due to the overlap with physiological immune immaturity and the high incidence of infections in early childhood. Clinicians must carefully distinguish between benign infection patterns and true immunodeficiencies to avoid missed diagnoses and unnecessary investigations. This review summarizes key findings on IgG subclass deficiency and specific antibody deficiency, highlights their clinical relevance in paediatric practice, and evaluates current challenges in diagnosis and classification. We also discuss the overlap between these conditions and propose a structured approach to improve diagnostic consistency. Addressing these knowledge gaps is essential to optimize care for children with recurrent infections and suspected antibody deficiencies.