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

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Kendirli P. K., Erdem Ş., Kısaarslan A. P., GÖK V., KAYHAN E., ÖZCAN A., ...More

Inflammation Research, vol.75, no.1, 2026 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 75 Issue: 1
  • Publication Date: 2026
  • Doi Number: 10.1007/s00011-026-02270-1
  • Journal Name: Inflammation Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE
  • Keywords: Deficiency in ELF4, ELF4, ITP, X-linked
  • Open Archive Collection: AVESIS Open Access Collection
  • Erciyes University Affiliated: Yes

Abstract

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.