2. Academic Validation
  3. Loss of Function Mutation in ELF4 Causes Autoinflammatory and Immunodeficiency Disease in Human

Loss of Function Mutation in ELF4 Causes Autoinflammatory and Immunodeficiency Disease in Human

  • J Clin Immunol. 2022 May;42(4):798-810. doi: 10.1007/s10875-022-01243-3.
Gan Sun 1 2 3,  Luyao Qiu 1 2 3,  Lang Yu 1 2 3,  Yunfei An 1 2 3 4,  Yuan Ding 1 2 3,  Lina Zhou 1 2 3,  Junfeng Wu 1 2 3 4,  Xi Yang 1 2 3 4,  Zhiyong Zhang 1 2 3 4,  Xuemei Tang 1 2 3 4,  Huawei Xia 5,  Lili Cao 5,  Fuping You 5,  Xiaodong Zhao 6 7 8 9,  Hongqiang Du 10 11 12 13
Affiliations

Affiliations

  • 1 National Clinical Research Center for Child Health and Disorders (Chongqing), Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China.
  • 5 Beijing Key Laboratory of Tumor Systems Biology, Department of Immunology, School of Basic Medical Sciences, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100000, China.
  • 6 National Clinical Research Center for Child Health and Disorders (Chongqing), Children's Hospital of Chongqing Medical University, Chongqing, China. zhaoxd530@aliyun.com.
  • 7 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. zhaoxd530@aliyun.com.
  • 8 Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China. zhaoxd530@aliyun.com.
  • 9 The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400014, China. zhaoxd530@aliyun.com.
  • 10 National Clinical Research Center for Child Health and Disorders (Chongqing), Children's Hospital of Chongqing Medical University, Chongqing, China. doctordo@aliyun.com.
  • 11 Ministry of Education Key Laboratory of Child Development and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China. doctordo@aliyun.com.
  • 12 Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, China. doctordo@aliyun.com.
  • 13 Department of Rheumatology & Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China. doctordo@aliyun.com.
PMID: 35266071 DOI: 10.1007/s10875-022-01243-3
Abstract

Monogenic autoinflammatory diseases (mAIDs) are a heterogeneous group of diseases affecting primarily innate immunity, with various genetic causes. Genetic diagnosis of mAIDs can assist in the patient's management and therapy. However, a large number of sporadic and familial cases remain genetically uncharacterized. Deficiency in ELF4, X-linked (DEX) is recently identified as a novel mAID. Here, we described a pediatric patient suffering from recurrent viral and Bacterial respiratory Infection, refractory oral ulcer, constipation, and arthritis. Whole-exome Sequencing found a hemizygous variant in ELF4 (chrX:129205133 A > G, c.691 T > C, p.W231R). Using cells from patient and point mutation mice, we showed mutant cells failed to restrict viral replication effectively and produced more pro-inflammatory cytokines. RNA-seq identified several potential critical Antiviral and anti-inflammation genes with decreased expression, and ChIP-qPCR assay suggested mutant ELF4 failed to bind to the promoters of these genes. Thus, we presented the second report of DEX.

Keywords

Autoinflammatory disease; ELF4; Immunodeficiency; Inborn errors of immunity; Loss of function.

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