Department of Rheumatology & Immunology, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Zhongshan Er Road 136Yuzhong District, Chongqing, China.
World J Pediatr. 2024 May;20(5):444-450. doi: 10.1007/s12519-024-00807-0. Epub 2024 May 11.
ELF4 deficiency has been recently recognized as a novel disorder within the spectrum of inborn errors of immunity (IEIs), specifically categorized as a "disease of immune dysregulation." Cases of this condition, reported by our team and others, are very limited worldwide. As such, our current knowledge of this new disease remains preliminary. This review aims to provide a brief overview of the clinical manifestations, pathogenesis, and treatment strategies for this novel IEI.
A comprehensive review was conducted after an extensive literature search in the PubMed/Medline database and websites concerning transcriptional factor ELF4 and reports concerning patients with ELF4 deficiency. Our search strategy was "ELF4 OR ETS-related transcription factor Elf-4 OR EL4-like factor 4 OR myeloid Elf-1-like factor" as of the time of manuscript submission.
The current signature manifestations of ELF4 deficiency disorder are recurrent and prolonged oral ulcer, abdominal pain, and diarrhea in pediatric males. In some cases, immunodeficiency and autoimmunity can also be prominent. Targeted Sanger sequencing or whole exome sequencing can be used to detect variation in ELF4 gene. Western blotting for ELF4 expression of the patient's cells can confirm the pathogenic effect of the variant. To fully confirm the pathogenicity of the variant, further functional test is strongly advised. Glucocorticoid and biologics are the mainstream management of ELF4 deficiency disorder.
Pediatric males presenting with recurring ulcerations in digestive tract epithelium with or without recurrent fever should be suspected of DEX. When atypical presentations are prominent, variations in ELF4 gene should be carefully evaluated functionally due to the complex nature of ELF4 function. Experience of treating DEX includes use of glucocorticoid and biologics and more precise treatment needs more patients to identify and further mechanistic study.
ELF4 缺乏症最近被认为是一种新的先天性免疫缺陷（IEI）疾病，具体归类为“免疫失调疾病”。我们团队和其他团队报告的这种疾病的病例在全球范围内非常有限。因此，我们对这种新疾病的了解仍然是初步的。本综述旨在简要概述这种新的 IEI 的临床表现、发病机制和治疗策略。
在对 PubMed/Medline 数据库和涉及转录因子 ELF4 的网站以及有关 ELF4 缺乏症患者的报告进行广泛文献检索后，进行了全面综述。我们的搜索策略是“ELF4 或 ETS 相关转录因子 Elf-4 或 EL4 样因子 4 或髓系 Elf-1 样因子”，截至提交手稿的时间。
ELF4 缺乏症的当前特征表现为儿科男性反复出现且持续时间较长的口腔溃疡、腹痛和腹泻。在某些情况下，免疫缺陷和自身免疫也可能很突出。可以使用靶向 Sanger 测序或全外显子组测序来检测 ELF4 基因的变异。患者细胞的 ELF4 表达的 Western 印迹可以确认变体的致病作用。为了充分确认变体的致病性，强烈建议进行进一步的功能测试。糖皮质激素和生物制剂是 ELF4 缺乏症的主流治疗方法。
出现消化道上皮反复溃疡伴或不伴反复发热的儿科男性应怀疑为 DEX。当不典型表现突出时，由于 ELF4 功能的复杂性，应仔细评估 ELF4 基因的变异是否具有功能。治疗 DEX 的经验包括使用糖皮质激素和生物制剂，更精确的治疗需要更多的患者来确定和进一步的机制研究。
