Successful Immune Reconstitution in a Patient with a <i>TYK2</i> Deficiency after Allogeneic Stem Cell Transplantation from Unrelated Donors

作者全名：Gao, Yelei; Wang, Ya; Zhou, Lina; Lv, Ge; Yu, Jie; Zhang, Luying; Meng, Yan; He, Wenli; Chen, Ran; Zhao, Xiaodong; Dou, Ying

作者地址：[Gao, Yelei; Wang, Ya; Zhou, Lina; Lv, Ge; Yu, Jie; Zhang, Luying; Meng, Yan; He, Wenli; Chen, Ran; Zhao, Xiaodong; Dou, Ying] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Rare Dis Infect & Immun, Minist Educ,Key Lab Child Dev & Disorders,China In, Chongqing 400014, Peoples R China; [Wang, Ya; Yu, Jie; Zhang, Luying; Meng, Yan; Dou, Ying] Chongqing Med Univ, Dept Hematol & Oncol, Childrens Hosp, Chongqing 400014, Peoples R China; [Lv, Ge; He, Wenli; Zhao, Xiaodong] Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing 400014, Peoples R China

通信作者：Zhao, XD; Dou, Y (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Rare Dis Infect & Immun, Minist Educ,Key Lab Child Dev & Disorders,China In, Chongqing 400014, Peoples R China.; Dou, Y (通讯作者)，Chongqing Med Univ, Dept Hematol & Oncol, Childrens Hosp, Chongqing 400014, Peoples R China.; Zhao, XD (通讯作者)，Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing 400014, Peoples R China.

来源：JOURNAL OF CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001250990500002

JCR分区：Q1

影响因子：7.2

年份：2024

卷号：44

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：TYK2; Primary immunodeficiency; Hematopoietic stem cell transplantation; Immune reconstitution

摘要：A boy with primary immunodeficiency, caused by a tyrosine kinase 2 (TYK2) mutation, presented with immune defects and a lifelong history of severe infections. Our aim was to determine whether allogeneic hematopoietic stem cell transplantation (HSCT) could restore the patient's immune defenses and reduce susceptibility to infection. In the absence of a suitable HLA-matched blood relative to act as a donor, the patient received an allogeneic HSCT from unrelated donors. The patient's clinical data were analyzed in the Children's Hospital of Chongqing Medical University (Chongqing, China) before transplantation and during the 4-year follow-up period using a combination of western blotting (e.g., TYK2 and STAT levels), qRT-PCR (e.g., T cell receptor rearrangement excision circles, kappa deletion element recombination circles, and TYK2 transcript levels), and flow cytometry (e.g., lymphocyte subpopulations and CD107 alpha secretion). We found that HSCT significantly reduced the incidence of severe infections, restored normal TKY2 levels, and reversed defects such as impaired JAK/STAT signaling in response to interferon-alpha or interleukin-10 treatment. Although the patient did not develop acute graft-versus-host disease (GVHD) after transplantation, he did experience chronic GVHD symptoms in a number of organs, which were effectively managed. Our findings suggest that HSCT is a feasible strategy for reconstituting the immune system in TYK2-deficient patients; however, the factors associated with GVHD and autoimmune thyroiditis development in TYK2-deficient patients undergoing HSCT warrant further investigation.

基金机构：Chongqing medical scientific research project

基金资助正文：We are grateful to the patient, the healthy donors, and their families for their cooperation in this study. We also thank the doctors, nurses, and all the laboratory staff for their hard work and assistance.