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A Multicenter Cohort Study of Immune Dysregulation Disorders Caused by ELF4 Variants in China

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Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Patients with DEX (deficiency in ELF4, X-linked) were recently reported by our team and others, and cases are very limited worldwide. Our knowledge of this new disease is currently preliminary. In this study, we described 5 more cases presenting mainly with oral ulcer, inflammatory bowel disease-like symptoms, fever of unknown origin, anemia, or systemic lupus erythematosus. Whole exome sequencing identified potential pathogenic ELF4 variants in all cases. The pathogenicity of these variants was confirmed by the detection of ELF4 expression in peripheral blood mononuclear cells from patients and utilizing a simple IFN-b luciferase reporter assay, as previously reported. Our findings significantly contribute to the current understanding of DEX.

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Data Availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

Code Availability

Not applicable.

Abbreviations

IEIs:

Inborn errors of immunity

ETS:

The E-twenty-six domain

DEX:

Deficiency in ELF4, X-linked

SLE:

Systemic lupus erythematosus

IVIG:

Intravenous immunoglobulin therapy

NSAIDs:

Nonsteroidal anti-inflammatory drugs

PBMCs:

Peripheral blood mononuclear cells

CADD:

Combined annotation dependent depletion

CMBI:

Centre for molecular and biomolecular informatics

MMP-9:

Matrix metalloproteinase-9

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Acknowledgements

We thank the patients and their families for their cooperation. We thank the members of our laboratory for their technical assistance.

Funding

This study is funded by the National Natural Science Foundation of China (82101908), Postdoc Fund of Chongqing Natural Science Foundation (cstc2021jcyj-bshX0226), General Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders (GBRP-202110), CQMU Program for Youth Innovation in Future Medicine (W0100), Sanming Project of Medicine in Shenzhen (SZSM201812002), Livelihood Project of Chongqing, China (cstc2018jscxmsybX0005).

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Authors and Affiliations

  1. National Clinical Research Center for Child Health and Disorders (Chongqing), Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Department of Rheumatology & Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, China

    Gan Sun, Xi Yang, Junfeng Wu, Wenjing Tang, Rongxin Dai, Lina Zhou, Yuan Ding, Zhiyong Zhang, Yunfei An, Xuemei Tang, Xiaodong Zhao & Hongqiang Du

  2. Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China

    Maolan Wu & Xiangrong Zheng

  3. Department of Rheumatology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China, Shanghai, China

    Qianying Lv & Li Sun

  4. Department of Gastroenterology, Shenzhen Children’s Hospital, Shenzhen, China

    Zhaoxia Wang

  5. Department of Pediatrics, West China Second University Hospital, Sichuan University, Sichuan province, Chengdu, China

    Yongmei Xie

  6. The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China

    Xiaodong Zhao

Authors
  1. Gan Sun
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  2. Maolan Wu
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  3. Qianying Lv
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  4. Xi Yang
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  7. Rongxin Dai
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  8. Lina Zhou
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  9. Yuan Ding
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  15. Li Sun
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  16. Yongmei Xie
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  17. Xiaodong Zhao
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  18. Hongqiang Du
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Contributions

HQ.D, XD.Z, YM.X, L.S, ZX.W, and XR.Z conceived and supervised the project, reviewed, and revised the manuscript; G.S performed the experiments, analyzed data, and wrote the manuscript; ML.W and QY.L followed the patients and collected clinical data. Others provided essential help for clinical management, follow-up of the patient, and valuable clinical expertise in reviewing the manuscript.

Corresponding authors

Correspondence to Xiangrong Zheng, Zhaoxia Wang, Li Sun, Yongmei Xie, Xiaodong Zhao or Hongqiang Du.

Ethics declarations

Ethics Approval

The ethics committee of Children’s Hospital of Chongqing Medical University, Children’s Hospital of Fudan University, Xiangya Hospital Central South University, West China Second University Hospital and Shenzhen Children’s Hospital approved the study. Blood sample collections were performed in accordance with the Declaration of Helsinki.

Consent to Participate

Written informed consent for participation in the study was obtained from patients’ parents.

Consent for Publication

Written informed consent for publication of the study was obtained from patients’ parents.

Conflict of Interest

The authors declare no competing interests.

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Sun, G., Wu, M., Lv, Q. et al. A Multicenter Cohort Study of Immune Dysregulation Disorders Caused by ELF4 Variants in China. J Clin Immunol 43, 933–939 (2023). https://doi.org/10.1007/s10875-023-01453-3

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