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/mm(3) over three months, we evaluated anti-neutrophil autoantibodies, 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 HNAla in 16 patients, HNAlc in 15, MHC Class I in 14, HNAlb 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 [Cys223stopl 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. (C) 2012 Elsevier GmbH. All rights reserved.