Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia.

Background: Patients with severe congenital neutropenia (SCN) often develop periodontitis despite standard medical and dental care. In light of previous findings that mutations in the neutrophil elastase gene, ELANE, are associated with more severe neutropenic phenotypes, we hypothesized an association between the genotype of SCN and development of periodontitis.

Methods: Fourteen Swedish patients with SCN or cyclic neutropenia harboring different genetic backgrounds were recruited for periodontal examination. Peripheral blood, gingival crevicular fluid (GCF), and subgingival bacterial samples were collected. The levels of cytokines and antibacterial peptides were determined in GCF and plasma by multiplex immunoassay and immunoblotting, respectively. Subgingival bacterial samples were analyzed using 16S rDNA pyrosequencing.

Results: ELANE mutations correlated with more severe periodontal status than the HAX1 or unknown mutations in patients with SCN. The subjects with mutant ELANE had higher levels of IL-1β in GCF. Using principal coordinate analysis of the subgingival microbiota, patients with ELANE mutations and reference subjects with periodontitis tended to cluster differently from patients with HAX1 or unknown mutations and non-periodontitis reference subjects.

Conclusion: This study demonstrates an association between ELANE mutations in SCN and the development of periodontitis with skewed subgingival microbiota, indicating a potential role of ELANE mutations in the pathogenesis of periodontitis.