Novel CD81 Mutations in a Chinese Patient Led to IgA Nephropathy and Impaired BCR Signaling

作者全名："Yang, Lu; Liu, Ping; Du, Hongqiang; Chen, Ran; Zhou, Bo; Li, Yanan; Zhou, Lina; Wang, Xiangli; Liu, Cuihua; Ding, Yuan; Tang, Xuemei; Chen, Yongwen; An, Yunfei; Zhao, Xiaodong"

作者地址："[Yang, Lu; Du, Hongqiang; Chen, Ran; Li, Yanan; Zhou, Lina; Ding, Yuan; Tang, Xuemei; An, Yunfei; Zhao, Xiaodong] Chongqing Med Univ, Childrens Hosp,Dept Pediat Res Inst,Minist Educ, China Int Sci & Technol Cooperat Base Child Dev &, Natl Clin Res Ctr Child Hlth & Disorders,Key Lab, Chongqing, Peoples R China; [Yang, Lu; Du, Hongqiang; Chen, Ran; Li, Yanan; Zhou, Lina; Ding, Yuan; Tang, Xuemei; An, Yunfei; Zhao, Xiaodong] Chongqing Med Univ, Chongqing Key Lab Child Infect & Immun, Childrens Hosp, Chongqing, Peoples R China; [Yang, Lu; Du, Hongqiang; Li, Yanan; Zhou, Lina; Ding, Yuan; Tang, Xuemei; An, Yunfei; Zhao, Xiaodong] Chongqing Med Univ, Div Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China; [Liu, Ping; Wang, Xiangli; Liu, Cuihua] Zhengzhou Univ, Henan Childrens Hosp, Zhengzhou Childrens Hosp, Dept Nephrol & Rheumatol,Childrens Hosp, Zhengzhou, Peoples R China; [Zhou, Bo] Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China; [Chen, Yongwen] Third Mil Med Univ, Inst Immunol, PLA, Chongqing, Peoples R China; [Zhao, Xiaodong] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："An, YF; Zhao, XD (通讯作者)，Chongqing Med Univ, Childrens Hosp,Dept Pediat Res Inst,Minist Educ, China Int Sci & Technol Cooperat Base Child Dev &, Natl Clin Res Ctr Child Hlth & Disorders,Key Lab, Chongqing, Peoples R China.; An, YF; Zhao, XD (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Child Infect & Immun, Childrens Hosp, Chongqing, Peoples R China.; An, YF; Zhao, XD (通讯作者)，Chongqing Med Univ, Div Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China.; Zhao, XD (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：JOURNAL OF CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000826863000001

JCR分区：Q1

影响因子：9.1

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Antibody deficiency; IgA nephropathy; CD81 deficiency; CD19; BCR signaling

摘要："Purpose CD81 deficiency is an extremely rare primary immunodeficiency disease characterized by severe and recurrent infections, IgA-related nephropathy, and profound hypogammaglobulinemia. Only one patient has been reported so far, and the pathogenesis remains unclear. Here, we identified a new case of CD81 deficiency and described its pathogenesis. Methods We analyzed the clinical, genetic, and immunological features of the patient with CD81 deficiency, and explored the pathogenesis of her antibody deficiencies. Results The major manifestation of this patient was unexpectedly not recurrent infections but IgA nephropathy with aberrant serum galactose-deficient IgA1. Whole-exome sequencing revealed novel biallelic mutations in CD81 gene that abolished the surface expression of CD81. B cells from the patient lack membrane CD19 and showed reduced switched memory B cells and transitional B cells. Decreased expression of key molecules pY and pBTK in BCR signaling were demonstrated by confocal microscopy. RNA sequencing revealed that genes associated with BCR signaling and immunoglobulins were downregulated in CD81-deficient B cells. In addition, the patient showed increased frequency of T follicular helper cells that biased to Th1-like subsets. Conclusion We reported the second patient with CD81 deficiency in the world and illustrated aberrant BCR signaling in the patient, therefore helping to unravel the mechanism of antibody deficiency in CD81-deficient patients."

基金机构：National Natural Science Foundation of China [82070135]; Graduate Mentor Team of Chongqing Municipal Education Commission [2019-0966]; General Project of Chongqing Natural Science Foundation [cstc2020jcyj-msxmX0607]; Future Medical Youth Innovation Team Development Support Program of CMU

基金资助正文："This work was supported by National Natural Science Foundation of China (grant number 82070135), Graduate Mentor Team of Chongqing Municipal Education Commission (grant number 2019-0966), General Project of Chongqing Natural Science Foundation (grant number cstc2020jcyj-msxmX0607), and Future Medical Youth Innovation Team Development Support Program of CMU."