Phenotype-specific immune profiles and outcomes in childhood autoimmune neutropenia: A 20-year cohort study

Childhood autoimmune neutropenia (AIN) encompasses heterogeneous entities; phenotype-specific immunological profiles and their relationship to infection outcomes remain incompletely defined. To characterise clinical, immunological and long-term outcomes across distinct phenotypes of childhood AIN. We conducted a retrospective cohort study of 112 children with antibody-confirmed AIN at a tertiary centre over 20 years. Patients were classified into three phenotypes: primary autoimmune neutropenia (pAIN), long-lasting neutropenia (LL-Np) and late-onset neutropenia (LO-Np). Outcomes included lymphocyte subsets, immunoglobulin levels, infection-related hospitalisation rates and time to resolution. The cohort comprised 90 pAIN (80.4%), 10 LL-Np (8.9%) and 12 LO-Np (10.7%) patients. LO-Np was characterised by higher neutrophil counts, marked leucopenia, multi-lineage lymphopenia (CD3+, CD4+, CD19+), frequent antinuclear antibodies (ANA) positivity (50%) and associated autoimmune disease (25%). No infection-related hospitalisations occurred in LO-Np (0.00/100 person-years [PY]; 95% confidence interval [CI] 0.00-2.30) versus 1.38/100 PY in pAIN and 5.58/100 PY in LL-Np. Immunoglobulin levels were normal across all patients. Median time to resolution was 19, 67 and 59 months in pAIN, LL-Np and LO-Np respectively (both p < 0.001 vs. pAIN). Late-onset AIN represents a distinct phenotype with systemic immune dysregulation and multi-lineage lymphopenia, yet paradoxically absence of infection-related hospitalisations, reflecting preserved humoral immunity. Phenotype-based stratification may guide clinical monitoring and therapeutic decisions.