Altered Functions of Neutrophils in Two Chinese Patients With Severe Congenital Neutropenia Type 4 Caused by G6PC3 Mutations

作者全名："Dai, Rongxin; Lv, Ge; Li, Wenyan; Tang, Wenjing; Chen, Junjie; Liu, Qiao; Yang, Lu; Zhang, Min; Tian, Zhirui; Zhou, Lina; Yan, Xin; Wang, Yating; Ding, Yuan; An, Yunfei; Zhang, Zhiyong; Tang, Xuemei; Zhao, Xiaodong"

作者地址："[Dai, Rongxin; Tang, Wenjing; Yan, Xin; Wang, Yating; An, Yunfei; Zhang, Zhiyong; Tang, Xuemei] Chongqing Med Univ, Childrens Hosp, Dept Rheumatol & Immunol, Chongqing, Peoples R China; [Dai, Rongxin; Lv, Ge; Li, Wenyan; Tang, Wenjing; Chen, Junjie; Liu, Qiao; Yang, Lu; Zhang, Min; Tian, Zhirui; Zhou, Lina; Yan, Xin; Wang, Yating; Ding, Yuan; An, Yunfei; Zhang, Zhiyong; Tang, Xuemei; Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China; [Dai, Rongxin; Lv, Ge; Li, Wenyan; Tang, Wenjing; Chen, Junjie; Liu, Qiao; Yang, Lu; Zhang, Min; Tian, Zhirui; Zhou, Lina; Yan, Xin; Wang, Yating; Ding, Yuan; An, Yunfei; Zhang, Zhiyong; Tang, Xuemei; Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, Key Lab Child Dev & Disorders, Minist Educ, Chongqing, Peoples R China; [Dai, Rongxin; Lv, Ge; Li, Wenyan; Tang, Wenjing; Chen, Junjie; Liu, Qiao; Yang, Lu; Zhang, Min; Tian, Zhirui; Zhou, Lina; Yan, Xin; Wang, Yating; Ding, Yuan; An, Yunfei; Zhang, Zhiyong; Tang, Xuemei; Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Child Infect & Immun, Chongqing, Peoples R China"

通信作者："Li, WY; Zhao, XD (corresponding author), Chongqing Med Univ, Childrens Hosp, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing, Peoples R China.; Li, WY; Zhao, XD (corresponding author), Chongqing Med Univ, Childrens Hosp, Key Lab Child Dev & Disorders, Minist Educ, Chongqing, Peoples R China.; Li, WY; Zhao, XD (corresponding author), Chongqing Med Univ, Childrens Hosp, Chongqing Key Lab Child Infect & Immun, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000675534400001

JCR分区：Q1

影响因子：7.3

年份：2021

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：G6PC3; neutrophils; severe congenital neutropenia; NETs; G-CSF treatment; apoptosis

摘要："Background SCN4 is an autosomal recessive disease caused by mutations in the G6PC3 gene. The clinical, molecular, and immunological features; function of neutrophils; and prognosis of patients with SCN4 have not been fully elucidated. Methods Two Chinese pediatric patients with G6PC3 mutations were enrolled in this study. Clinical data, genetic and immunologic characteristics, and neutrophil function were evaluated in patients and controls before and after granulocyte colony-stimulating factor (G-CSF) treatment. Results Both patients had histories of pneumonia, inguinal hernia, cryptorchidism, and recurrent oral ulcers. Patient 1 also had asthma and otitis media, and patient 2 presented with prominent ectatic superficial veins and inflammatory bowel disease. DNA sequencing demonstrated that both patients harbored heterozygous G6PC3 gene mutations. Spontaneous and FAS-induced neutrophil apoptosis were significantly increased in patients, and improved only slightly after G-CSF treatment, while neutrophil respiratory burst and neutrophil extracellular traps production remained impaired in patients after G-CSF treatment. Conclusion G-CSF treatment is insufficient for patients with SCN4 patients, who remain at risk of infection. Where possible, regular G-CSF treatment, long-term prevention of infection, are the optimal methods for cure of SCN4 patients. It is important to monitor closely for signs of leukemia in SCN4 patients. Once leukemia occurs in SCN4 patients, hematopoietic stem cell transplantation is the most important choice of treatment."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81801637, 81620108014]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (81801637, 81620108014)."