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Objective and design <p>In this report, we identified a novel hemizygous <i>ELF4</i> variant (c.1822G &gt; C; p.Gly608Arg) in an adolescent male with chronic immune thrombocytopenia (ITP) and performed functional immunologic characterization. </p> Materials and methods <p>Peripheral blood mononuclear cells (PBMCs) of the patient and age-matched controls were characterized by flow cytometry with respect to T cell phenotype, activation, proliferation and NK cell cytotoxicity.</p> Results <p>The p.Gly608Arg substitution affects a highly conserved residue in the C-terminal regulatory domain of <i>ELF4</i> and is predicted to be damaging. Immunophenotyping showed an expanded CD8<sup>+</sup> T-cell compartment, an inverted CD4/CD8 ratio, reduced naïve T-cell populations, and accelerated acquisition of memory-like phenotypes upon activation. Both CD4<sup>+</sup> and CD8<sup>+</sup> T cells displayed increased proliferation following TCR stimulation, consistent with impaired <i>ELF4</i>-dependent regulation of effector T-cell expansion. NK cells exhibited reduced granzyme B and perforin expression and markedly diminished cytotoxicity against K562 targets, indicating defects in maturation and effector function.</p> Conclusions <p>These findings suggest that the identified ELF4 variant is associated with combined T- and NK-cell dysfunction. This case expands the clinical spectrum of Deficiency in <i>ELF4</i>,<i> X-linked</i> and underscores the relevance of evaluating <i>ELF4</i> mutations in patients with unexplained cytopenias accompanied by dysregulated lymphocyte activation and impaired cytotoxic responses.</p>

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A novel ELF4 gene variant disrupts T and NK cell function in a patient with immune thrombocytopenia (ITP)

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Perihan Kader Kendirli,
  • Şerife Erdem,
  • Ayşenur Paç Kısaarslan,
  • Veysel Gök,
  • Eda Kayhan,
  • Alper Özcan,
  • Muhammet Ensar Dogan,
  • Christoph Klein,
  • Ekrem Ünal,
  • Ahmet Eken

摘要

Objective and design

In this report, we identified a novel hemizygous ELF4 variant (c.1822G > C; p.Gly608Arg) in an adolescent male with chronic immune thrombocytopenia (ITP) and performed functional immunologic characterization.

Materials and methods

Peripheral blood mononuclear cells (PBMCs) of the patient and age-matched controls were characterized by flow cytometry with respect to T cell phenotype, activation, proliferation and NK cell cytotoxicity.

Results

The p.Gly608Arg substitution affects a highly conserved residue in the C-terminal regulatory domain of ELF4 and is predicted to be damaging. Immunophenotyping showed an expanded CD8+ T-cell compartment, an inverted CD4/CD8 ratio, reduced naïve T-cell populations, and accelerated acquisition of memory-like phenotypes upon activation. Both CD4+ and CD8+ T cells displayed increased proliferation following TCR stimulation, consistent with impaired ELF4-dependent regulation of effector T-cell expansion. NK cells exhibited reduced granzyme B and perforin expression and markedly diminished cytotoxicity against K562 targets, indicating defects in maturation and effector function.

Conclusions

These findings suggest that the identified ELF4 variant is associated with combined T- and NK-cell dysfunction. This case expands the clinical spectrum of Deficiency in ELF4, X-linked and underscores the relevance of evaluating ELF4 mutations in patients with unexplained cytopenias accompanied by dysregulated lymphocyte activation and impaired cytotoxic responses.