title: Identifying patients with neutrophil elastase (ELANE) mutations from patients with a presumptive diagnosis of autoimmune neutropenia.
abstract: 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 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.
authors.affiliation: Primary Immunodeficiency Care And Research (PICAR) Institute, Chang Gung University, College of Medicine and Memorial Hospital Taoyuan, Taiwan. wen2707@hotmail.com
authors.forename: Wen-I
authors.initials: WI
authors.lastname: Lee
authors.forename: Shih-Hsiang
authors.initials: SH
authors.lastname: Chen
authors.forename: Jing-Long
authors.initials: JL
authors.lastname: Huang
authors.forename: Tang-Her
authors.initials: TH
authors.lastname: Jaing
authors.forename: Hung-Tao
authors.initials: HT
authors.lastname: Chung
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Yeh
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Chen
authors.forename: Tsung-Chieh
authors.initials: TC
authors.lastname: Yao
authors.forename: Meng-Ying
authors.initials: MY
authors.lastname: Hsieh
authors.forename: Syh-Jae
authors.initials: SJ
authors.lastname: Lin
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D000080984:Congenital Bone Marrow Failure Syndromes; D003937:Diagnosis, Differential; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D007519:Isoantigens / Q000235:genetics / Q000276:immunology; D019272:Leukocyte Elastase / Q000235:genetics* / Q000276:immunology; D008297:Male; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D011956:Receptors, Cell Surface; C067704:neutrophil-specific antigen NA1, human; C104384:neutrophil-specific antigen SH; D019272:Leukocyte Elastase