ABSTRACT
Cyclic neutropenia (CyN) is a rare, ELANE-related neutropenia. Oral manifestations are among the initial signs of CyN and an important reason that leads patients to seek professional help. This case report describes a 12-year-old girl with recurrent oral ulcers, severe chronic periodontitis, and pathological tooth migration as the initial and main clinical symptoms of CyN. Two novel mutations in ELANE, c.180T>G (p.I60M) and c.182C>G (p.A61G) associated with CyN were observed. Bioinformatics research indicated lower stability and impaired molecular linkages of the mutant neutrophil elastase (NE) encoded by ELANE. However, the enzyme affinity to the classic substrate Suc-Ala-Ala-Ala-pNA was not substantially changed, suggesting that the impaired integrity and stability of the mutant NE, rather than catalytic deficiency, might be the pathogenic mechanism of ELANE mutation-induced neutropenia. The patient was prescribed scaling and root planing (SRP) and monthly periodontal maintenance without systemic management. Although the routine periodontal treatment was occasionally interrupted by the 2019 coronavirus pandemic, her periodontal devastation remained well-remitted in the 5-year follow-up assessment. The results of this study confirmed the importance of plaque control and proper diagnosis in the periodontal management of such patients and provide better clinical references. In addition, the novel mutations identified in this study expand the spectrum of known ELANE mutations in CyN and further contribute to knowledge regarding its pathogenic mechanism.
ABSTRACT
Background and Aims: All components of the immune system are involved in alleviating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further research is required to provide detailed insights into COVID-19-related immune compartments and pathways. In addition, a significant percentage of hospitalized COVID-19 patients suspect bacterial infections and antimicrobial resistance occurs following antibiotics treatment. The aim of this study was to evaluate the possible effects of antibiotics on the response of neutrophil-related genes in SARS-CoV-2 patients by an experimental in silico study. Methods: The two data sets GSE1739 and GSE21802 including 10 SARS positive patients and 35 influenza A (H1N1) patients were analyzed, respectively. Differentially expressed genes (DEGs) between these two data sets were determined by GEO2R analysis and the Venn diagram online tool. After determining the hub genes involved in immune responses, the expression of these genes in 30 COVID-19 patients and 30 healthy individuals was analyzed by real-time polymerase chain reaction (PCR). All patients received antibiotics, including levofloxacin, colistin, meropenem, and ceftazidime. Results: GEO2R analysis detected 240 and 120 DEGs in GSE21802 and GSE1739, respectively. Twenty DEGs were considered as enriched hub genes involved in immune processes such as neutrophil degranulation, neutrophil activation, and antimicrobial humoral response. The central nodes were attributed to the genes of neutrophil elastase (ELANE), arginase 1 (ARG-1), lipocalin 2 (LCN2), and defensin 4 (DEFA4). Compared to the healthy subjects, the expression of LCN2 and DEFA4 were significantly reduced in COVID-19 patients. However, no significant differences were observed in the ELANE and AGR-1 levels between COVID-19 subjects and the control group. Conclusions: Activation and degranulation of neutrophils were observed mainly in SARS, and H1N1 infection processes and antibiotics administration could affect neutrophil activity during viral infection. It can be suggested that antibiotics can decrease inflammation by restoring the expression of neutrophil-related genes in COVID-19 patients.