Pediatric selective IgM deficiency: clinical features and a preliminary risk index for immunoglobulin replacement therapy.

Selective immunoglobulin M deficiency (SIgMD) is a rare pediatric antibody defect with poorly defined thresholds for immunoglobulin replacement therapy (IgRT). We retrospectively reviewed 5,122 serum IgM measurements (2005–2024) and identified 21 children meeting SIgMD criteria (IgM < 20 mg/dL with normal IgG/IgA). Nine had isolated SIgMD, while 12 presented with comorbid conditions. Recurrent tonsillopharyngitis was more frequent in isolated cases, whereas low isohaemagglutinin titres and lymphopenia were confined to the comorbidity group. IgRT was initiated in 11 patients, predominantly those with comorbidities (75% vs. 22%). Firth-penalised logistic regression confirmed comorbidity as the only independent correlation of IgRT. An exploratory four-parameter framework (comorbidity, isohaemagglutinin titres, lymphopenia, baseline IgA) achieved good discrimination for predicting treatment need (AUC = 0.80, optimism-adjusted AUC = 0.80). These findings suggest that routine laboratory markers may help identify children at higher risk of requiring IgRT, but validation in larger multicentre cohorts is essential.