PubMed İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/397
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Article A Novel ELF4 Gene Variant Disrupts T and NK Cell Function in a Patient with Immune Thrombocytopenia (ITP)(Springer Basel AG, 2026) Kendirli, Perihan Kader; Gök, Veysel; Eken, Ahmet; Özcan, Alper; Erdem, Şerife; Kısaarslan, Ayşenur Paç; Kayhan, EdaObjective 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 na & iuml;ve 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.Article Citation - WoS: 3Citation - Scopus: 3Alantolactone Ameliorates Graft Versus Host Disease in Mice(Elsevier, 2024-02) Odabas, Gul Pelin; Aslan, Kubra; Suna, Pinar Alisan; Kendirli, Perihan Kader; Erdem, Serife; Cakir, Mustafa; Unal, EkremThe anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naive (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naive phenotype (CD62L+ CD44-). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.