{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:20:00Z","timestamp":1788787200265,"version":"build-2803163510"},"reference-count":9,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003062","name":"Erciyes University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflamm. Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective and design<\/jats:title>\n                    <jats:p>\n                      In this report, we identified a novel hemizygous\n                      <jats:italic>ELF4<\/jats:italic>\n                      variant (c.1822G\u2009&gt;\u2009C; p.Gly608Arg) in an adolescent male with chronic immune thrombocytopenia (ITP) and performed functional immunologic characterization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The p.Gly608Arg substitution affects a highly conserved residue in the C-terminal regulatory domain of\n                      <jats:italic>ELF4<\/jats:italic>\n                      and is predicted to be damaging. Immunophenotyping showed an expanded CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell compartment, an inverted CD4\/CD8 ratio, reduced na\u00efve T-cell populations, and accelerated acquisition of memory-like phenotypes upon activation. Both CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells displayed increased proliferation following TCR stimulation, consistent with impaired\n                      <jats:italic>ELF4<\/jats:italic>\n                      -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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>ELF4<\/jats:italic>\n                      ,\n                      <jats:italic>X-linked<\/jats:italic>\n                      and underscores the relevance of evaluating\n                      <jats:italic>ELF4<\/jats:italic>\n                      mutations in patients with unexplained cytopenias accompanied by dysregulated lymphocyte activation and impaired cytotoxic responses.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-026-02270-1","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T02:55:49Z","timestamp":1779159349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel ELF4 gene variant disrupts T and NK cell function in a patient with immune thrombocytopenia (ITP)"],"prefix":"10.1007","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4324-5196","authenticated-orcid":false,"given":"Perihan Kader","family":"Kendirli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eerife","family":"Erdem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fenur Pa\u00e7","family":"K\u0131saarslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veysel","family":"G\u00f6k","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eda","family":"Kayhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alper","family":"\u00d6zcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammet Ensar","family":"Dogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2691-4826","authenticated-orcid":false,"given":"Ekrem","family":"\u00dcnal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5816-0686","authenticated-orcid":false,"given":"Ahmet","family":"Eken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"2270_CR1","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/s41590-021-00984-4","volume":"22","author":"PM Tyler","year":"2021","unstructured":"Tyler PM, Bucklin ML, Zhao M, Maher TJ, Rice AJ, Ji W, et al. Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation. Nat Immunol Nat Res. 2021;22:1118\u201326. https:\/\/doi.org\/10.1038\/s41590-021-00984-4.","journal-title":"Nat Immunol Nat Res"},{"key":"2270_CR2","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1007\/s10875-023-01453-3","volume":"43","author":"G Sun","year":"2023","unstructured":"Sun G, Wu M, Lv Q, Yang X, Wu J, Tang W, et al. A multicenter cohort study of immune dysregulation disorders caused by ELF4 variants in China. J Clin Immunol Springer. 2023;43:933\u20139. https:\/\/doi.org\/10.1007\/s10875-023-01453-3.","journal-title":"J Clin Immunol Springer"},{"key":"2270_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.mucimm.2025.09.007","author":"C Tian","year":"2025","unstructured":"Tian C, Ye X, Xiong S, Mohapatra G, Lin S, Ye Z, et al. Novel loss-of-function intronic mutation in ELF4 is associated with intestinal autoinflammation. Mucosal Immunol [Internet]. 2025. https:\/\/doi.org\/10.1016\/j.mucimm.2025.09.007.","journal-title":"Mucosal Immunol [Internet]"},{"key":"2270_CR4","doi-asserted-by":"crossref","unstructured":"Lacorazza HD, Miyazaki Y, Di Cristofano A, Deblasio A, Hedvat C, Zhang J, Cordon-Cardo C, Mao S, Pandolfi PP, Nimer SD. The ETS protein MEF plays a critical role in perforin gene expression and the development of natural killer and NK-T cells. Immunity. 2002; 17:437","DOI":"10.1016\/S1074-7613(02)00422-3"},{"key":"2270_CR5","doi-asserted-by":"publisher","unstructured":"Salinas SA, Mace EM, Conte MI, Park CS, Li Y, Rosario-Sepulveda JI, et al. An ELF4 hypomorphic variant results in NK cell deficiency. JCI Insight Am Soc Clin Invest. 2022. https:\/\/doi.org\/10.1172\/jci.insight.155481.","DOI":"10.1172\/jci.insight.155481"},{"key":"2270_CR6","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1038\/ni.1730","volume":"10","author":"T Yamada","year":"2009","unstructured":"Yamada T, Park CS, Mamonkin M, Lacorazza HD. Transcription factor ELF4 controls the proliferation and homing of CD8\u2009+\u2009T cells via the Kr\u00fcppel-like factors KLF4 and KLF2. Nat Immunol. 2009;10:618\u201326. https:\/\/doi.org\/10.1038\/ni.1730.","journal-title":"Nat Immunol"},{"key":"2270_CR7","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1038\/ni.2756","volume":"14","author":"F You","year":"2013","unstructured":"You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, et al. ELF4 is critical for induction of type i interferon and the host antiviral response. Nat Immunol. 2013;14:1237\u201346. https:\/\/doi.org\/10.1038\/ni.2756.","journal-title":"Nat Immunol"},{"key":"2270_CR8","doi-asserted-by":"publisher","unstructured":"Lee P-H, Puppi M, Schluns KS, Yu-Lee L-Y, Dong C, Lacorazza HD. The transcription factor E74-like factor 4 suppresses differentiation of proliferating CD4\u2009+\u2009T cells to the Th17 lineage. J Immunol 2014;192:178\u201388. https:\/\/doi.org\/10.4049\/jimmunol.1301372.","DOI":"10.4049\/jimmunol.1301372"},{"key":"2270_CR9","doi-asserted-by":"publisher","unstructured":"Tokuriki N, Tawfik DS. Stability effects of mutations and protein evolvability. Curr Opin Struct Biol. 2009. https:\/\/doi.org\/10.1016\/j.sbi.2009.08.003.","DOI":"10.1016\/j.sbi.2009.08.003"}],"container-title":["Inflammation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-026-02270-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00011-026-02270-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-026-02270-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T02:55:52Z","timestamp":1779159352000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00011-026-02270-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":9,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2270"],"URL":"https:\/\/doi.org\/10.1007\/s00011-026-02270-1","relation":{},"ISSN":["1420-908X"],"issn-type":[{"value":"1420-908X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]},"assertion":[{"value":"8 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"115"}}