Expanding the Spectrum of Selective IgM Deficiency: From Infections to Immune Dysregulation

Area of Science:

• Immunology
• Clinical Medicine

Background:

• Immunoglobulin M (IgM) is critical for early immune responses.
• Selective IgM deficiency (sIgMD) diagnostic criteria focus on infections, potentially missing other manifestations.

Purpose of the Study:

• To analyze clinical features and molecular diagnoses in a pediatric cohort with isolated IgM deficiency, regardless of infection history.
• To challenge current sIgMD definitions and explore the heterogeneity of IgM deficiency.

Main Methods:

• Retrospective analysis of a pediatric cohort with isolated IgM deficiency.
• Evaluation of clinical features, infectious history, and molecular diagnoses.
• Longitudinal assessment of IgM concentration dynamics.

Main Results:

• Non-infectious manifestations (cytopenia, autoimmunity, etc.) were common and not solely linked to infections.
• 26% of patients received molecular diagnoses for inborn errors of immunity (IEIs), some without infections.
• IgM levels showed dynamic changes over time, classifiable into distinct subtypes.

Conclusions:

• Isolated IgM deficiency represents a broader immunological phenotype than sIgMD.
• Relying solely on infectious history limits diagnosis; molecular testing and extended follow-up are vital.
• A redefinition of IgM deficiency is necessary to encompass diverse clinical presentations and underlying IEIs.