Transient hypogammaglobulinemia of infancy: revisiting an old entity

Introduction Transient hypogammaglobulinemia of infancy (THI) is one of the most common primary antibody deficiencies presenting in early childhood and is characterized by delayed maturation of humoral immunity with spontaneous normalization of immunoglobulin G (IgG) levels in most patients. Although THI has traditionally been considered a benign, self-limited disorder, increasing evidence suggests that it represents a heterogeneous immunologic condition with variable clinical manifestations, immune abnormalities, and long-term outcomes.Areas covered This narrative review summarizes evidence identified through PubMed/MEDLINE searches from database inception to July 2026 using terms related to THI, supplemented by manual screening of reference lists. Clinical manifestations range from asymptomatic disease to recurrent respiratory tract infections, wheezing, otitis media, sinusitis, atopic disease, and, less commonly, autoimmune or inflammatory complications. A major clinical challenge is differentiating THI from persistent primary antibody deficiencies, particularly common variable immunodeficiency, during early childhood. Because definitive diagnosis can only be established retrospectively after normalization of immunoglobulin levels, careful longitudinal clinical and immunologic follow-up remains essential.Expert opinion Advances in immunophenotyping and molecular profiling are improving our understanding of THI pathogenesis and may facilitate the identification of biomarkers that distinguish transient immune delay from evolving primary immunodeficiency, supporting earlier diagnosis and more individualized follow-up.