Identifying patients with neutrophil elastase (ELANE) mutations from patients with a presumptive diagnosis of autoimmune neutropenia

To differentiate severe congenital neutropenia (SCN) from autoimmune neutropenia (AIN) in patients with persistent neutropenia ≤1000/mm3 over three months, we evaluated anti-neutrophil auto-antibodies, candidate genes of ELANA, HAX1 and GCSFR, and neutrophil elastase (NE) activity in 38 patients (21 females; average onset age 14.12 ± 2.49 months) in a primary immunodeficiency disease center between 2004 and 2011. In 30 patients, detectable anti-neutrophil auto-antibodies were HNA1a in 16 patients, HNA1c in 15, MHC Class I in 14, HNA1b in eight, MHC Class II in five, and HNA2a in three. Their average neutropenia duration was 27.04 ± 2.08 months. Of eight patients without detectable auto-antibodies, three had ELANE mutations [Ser126Pro, Arg170Phe and Cys223stop] and recurrent muco-cutaneous infections and sepsis. The patient with nonsense ELANE mutation [Cys223stop] had the lowest NE activity (16.8). Thus, patients with ELANE mutations have undetectable antibodies and more severe and younger-onset muco-cutaneous infections, prolonged healing and decreased serum NE activity that require prompt intervention.