{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:46Z","timestamp":1783574146792,"version":"3.55.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Coffin-Siris syndrome type 2 (CSS2), caused by\n                      <jats:italic>ARID1A<\/jats:italic>\n                      mutations, is characterized by neurodevelopmental delay and recurrent infections. The\n                      <jats:italic>ARID1A<\/jats:italic>\n                      p.Ala1077Glu variant has been linked to CSS2, but the immune mechanisms underlying infection susceptibility remain poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The variant was identified by trio-based whole-exome sequencing and confirmed by Sanger sequencing. Immune status was assessed via serum immunoglobulins, complement measurements, and flow cytometric immunophenotyping. RNA sequencing was performed on PMA-stimulated PBMCs from the patient and healthy controls, with key findings validated by qRT-PCR and ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immune profiling revealed widespread quantitative deficits across innate and adaptive compartments, with particularly marked reductions in NKT-like cells (CD3\n                      <jats:sup>+<\/jats:sup>\n                      CD56\n                      <jats:sup>+<\/jats:sup>\n                      ) and CD8\n                      <jats:sup>+<\/jats:sup>\n                      central memory T cells. Transcriptomic analysis of stimulated cells uncovered a profound activation defect, characterized by widespread downregulation of effector immune genes. Furthermore, pathway enrichment analysis demonstrated significant suppression of multiple biological processes critically dependent on IFN-\u03b3 signaling, such as antigen processing and presentation, and Th1\/Th17 cell differentiation. Expression of\n                      <jats:italic>IFNG<\/jats:italic>\n                      ,\n                      <jats:italic>STAT1<\/jats:italic>\n                      , and\n                      <jats:italic>CXCL9<\/jats:italic>\n                      showed a trend toward decreased expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest an association between the ARID1A p.Ala1077Glu variant and impaired IFN-\u03b3-mediated immunity in CSS2, potentially contributing to recurrent infections. The IFN-\u03b3 pathway warrants further investigation as a therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1803570","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:21:29Z","timestamp":1783570889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired IFN-\u03b3-mediated innate and adaptive immunity in Coffin-Siris syndrome type 2: immunological insights from a patient with a recurrent ARID1A mutation"],"prefix":"10.3389","volume":"17","author":[{"given":"Qi","family":"Peng","sequence":"first","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dongguan Maternal and Child Health Care Hospital","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaozhong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siping","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baimao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Dongguan Maternal and Child Health Care Hospital","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Lu","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dongguan Children\u2019s Hospital Affiliated to Guangdong Medical University","place":["Dongguan, Guangdong, China"]},{"name":"Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics","place":["Dongguan, Guangdong, China"]},{"name":"Key Laboratory for Children\u2019s Genetics and Infectious Diseases of Dongguan","place":["Dongguan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35415","article-title":"The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases","author":"Schrier","year":"2012","journal-title":"Am J Med Genet A"},{"key":"B2","first-page":"1993","article-title":"Coffin-siris syndrome","volume-title":"Genereviews\u00ae","author":"Schrier Vergano","year":"2013"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/genes12060937","article-title":"Genotype-phenotype correlations in 208 individuals with Coffin-Siris syndrome","volume":"12","author":"Vasko","year":"2021","journal-title":"Genes (Basel)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31407","article-title":"Genotype-phenotype correlation of Coffin-Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A","author":"Kosho","year":"2014","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63540","article-title":"ARID2, a milder cause of Coffin-Siris syndrome? 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