Multiple Immune Defects in Two Patients with Novel DOCK2 Mutations Result in Recurrent Multiple Infection Including Live Attenuated Virus Vaccine

作者全名："Li, Wenhui; Sun, Yuting; Yu, Lang; Chen, Ran; Gan, Rui; Qiu, Luyao; Sun, Gan; Chen, Junjie; Zhou, Lina; Ding, Yuan; Du, Hongqiang; Shu, Zhou; Zhang, Zhiyong; Tang, Xuemei; Chen, Yongwen; Zhao, Xiaodong; Zhao, Qin; An, Yunfei"

作者地址："[Li, Wenhui; Yu, Lang; Chen, Ran; Gan, Rui; Qiu, Luyao; Sun, Gan; Chen, Junjie; Zhou, Lina; Ding, Yuan; Du, Hongqiang; Zhang, Zhiyong; Tang, Xuemei; Zhao, Xiaodong; Zhao, Qin; An, Yunfei] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders Chongqing, Childrens Hosp, Chongqing, Peoples R China; [Li, Wenhui; Yu, Lang; Chen, Ran; Gan, Rui; Qiu, Luyao; Sun, Gan; Chen, Junjie; Zhou, Lina; Ding, Yuan; Du, Hongqiang; Zhang, Zhiyong; Tang, Xuemei; Zhao, Xiaodong; Zhao, Qin; An, Yunfei] Chongqing Med Univ, Key Lab Child Dev & Disorders, Minist Educ, Childrens Hosp, Chongqing, Peoples R China; [Li, Wenhui; Yu, Lang; Chen, Ran; Gan, Rui; Qiu, Luyao; Sun, Gan; Chen, Junjie; Zhou, Lina; Ding, Yuan; Du, Hongqiang; Shu, Zhou; Zhang, Zhiyong; Tang, Xuemei; Zhao, Xiaodong; Zhao, Qin; An, Yunfei] Chongqing Med Univ, Chongqing Key Lab Child Infect & Immun, Childrens Hosp, Chongqing, Peoples R China; [Sun, Yuting] Chongqing Univ, Sch Med, Chongqing, Peoples R China; [Du, Hongqiang; Zhang, Zhiyong; Tang, Xuemei; An, Yunfei] Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China; [Chen, Yongwen] Third Mil Med Univ, Inst Immunol, PLA, Chongqing 400014, Peoples R China"

通信作者："Zhao, Q; An, YF (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders Chongqing, Childrens Hosp, Chongqing, Peoples R China.; Zhao, Q; An, YF (通讯作者)，Chongqing Med Univ, Key Lab Child Dev & Disorders, Minist Educ, Childrens Hosp, Chongqing, Peoples R China.; Zhao, Q; An, YF (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Child Infect & Immun, Childrens Hosp, Chongqing, Peoples R China.; An, YF (通讯作者)，Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China."

来源：JOURNAL OF CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000951320000001

JCR分区：Q1

影响因子：7.2

年份：2023

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期号：　

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文献类型：Article; Early Access

关键词：DOCK2 deficiency; Combined immunodeficiency (CID); Recurrent infection; Live attenuated vaccine related infections

摘要："The dedicator of cytokinesis 2(DOCK2) protein, an atypical guanine nucleotide exchange factor (GEFs), is a member of the DOCKA protein subfamily. DOCK2 protein deficiency is characterized by early-onset lymphopenia, recurrent infections, and lymphocyte dysfunction, which was classified as combined immune deficiency with neutrophil abnormalities as well. The only cure is hematopoietic stem cell transplantation. Here, we report two patients harboring four novel DOCK2 mutations associated with recurrent infections including live attenuated vaccine-related infections. The patient's condition was partially alleviated by symptomatic treatment or intravenous immunoglobulin. We also confirmed defects in thymic T cell output and T cell proliferation, as well as aberrant skewing of T/B cell subset TCR-V beta repertoires. In addition, we noted neutrophil defects, the weakening of actin polymerization, and BCR internalization under TCR/BCR activation. Finally, we found that the DOCK2 protein affected antibody affinity although with normal total serum immunoglobulin. The results reported herein expand the clinical phenotype, the pathogenic DOCK2 mutation database, and the immune characteristics of DOCK2-deficient patients."

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