Autoimmune neutropenia in children: Test cells versus beads and a role for pro‐ LL ‐37 and absolute neutrophil count

Autoimmune neutropenia (AIN) in early childhood is caused by autoantibodies targeting neutrophil surface antigens, most commonly CD16 (FCGR3B), and must be distinguished from congenital neutropenia, malignancy-associated neutropenia and chronic idiopathic neutropenia (CIN). In this study, the diagnostic performance of the cell-based granulocyte agglutination test (GAT) and granulocyte immunofluorescence test (GIFT) was compared with the bead-based LabScreen Multi (LSM) assay in 214-suspected AIN cases. While 36% of samples were positive for anti-CD16 antibodies in GAT or GIFT, only 19% reacted against the same antigen in LSM, primarily against weak or Immunoglobulin M (IgM)-restricted antibody responses. Patients testing positive in all three assays exhibited significantly higher pro-LL-37 levels and lower absolute neutrophil counts (ANCs), indicating preserved granulopoiesis with peripheral destruction. Our findings question the use of LSM as a standalone test in AIN diagnostics. Incorporating pro-LL-37 and ANC in AIN diagnosis may improve differentiation between antibody-mediated neutropenia and other neutropenia forms in children.