{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T07:46:57Z","timestamp":1782200817523,"version":"3.54.5"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>RIPK1\u2010associated autoinflammatory diseases are monogenic autoinflammatory diseases with two distinct phenotypes: a severe immune deficiency form due to homozygous loss\u2010of\u2010function mutations, and a milder form, known as CRIA (Cleavage\u2010Resistant RIPK1\u2010Induced Autoinflammatory syndrome), due to heterozygous gain\u2010of\u2010function mutations within the caspase\u20108 cleavage site. Diagnosis can be challenging, particularly in cases with atypical presentations, leading to significant delays in providing appropriate care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We describe a patient with a novel heterozygous mutation within the RIPK1 kinase domain. She presented, since infancy, recurrent infections of the sinuses, bronchi, and lungs, along with hypogammaglobulinaemia and lymphopenia with relative effectiveness of subcutaneous immunoglobulin supplementation. As an adult, she developed severe autoimmune cytopenia and lymphoid hyperplasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Next\u2010generation sequencing by panel and whole\u2010exome analysis revealed a novel heterozygous D24V\n                      <jats:italic>RIPK1<\/jats:italic>\n                      pathogenic variant. Functional assays demonstrated low expression of Interleukin (IL)\u20102 and overexpression of IL\u20108 in patient peripheral blood mononuclear cells with LPS stimulation. A higher level of IL\u20106 in B\u2010lymphoblastoid cell lines (B\u2010LCL) suggested a role for B cells in the pathogenesis of this RIPK1\u2010associated disease. Functionally, Rituximab induced a shift in pro\u2010inflammatory cytokine secretion, specifically promoting a TH1 to TH2 switch. Unlike the immune deficiency forms and CRIA syndromes, the patient showed no impairment in the NF\u2010\u0138B pathway and a failure in cell death.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case highlights a new pattern of RIPKI\u2010related disease characterized by combined immunodeficiency, autoimmunity, and inflammation. It underscores the critical importance of early genetic diagnosis in pediatric patients with atypical presentations to avoid decades of morbidity and enable access to targeted, life\u2010changing therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.70302","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:36:48Z","timestamp":1773002208000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An unusual case of RIPK1\u2010related immunodeficiency: The importance of a timely diagnosis for a novel clinical and therapeutic pattern"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1969-6185","authenticated-orcid":false,"given":"Anne\u2010Sophie","family":"Parentelli","sequence":"first","affiliation":[{"name":"Service de P\u00e9diatrie, CHU F\u00e9lix Guyon  Saint\u2010Denis France"},{"name":"INSERM U1163, Institut Imagine Universit\u00e9 Paris\u2010Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Aur\u00e9lie","family":"Lopes","sequence":"additional","affiliation":[{"name":"Service des Urgences P\u00e9diatriques, AP\u2010HP, Centre Hospitalo\u2010Universitaire Necker\u2010Enfants\u2010Malades Universit\u00e9 de Paris  Paris France"},{"name":"INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades, Team Host\u2010Pathogen Integrative Biology Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Bastard","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\u2010Immunology and Rheumatology Unit, Necker Hospital AP\u2010HP Centre \u2010 Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute Paris Cit\u00e9 University  Paris France"},{"name":"St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch The Rockefeller University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Bizien","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute Paris Cit\u00e9 University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-0984","authenticated-orcid":false,"given":"Vincent","family":"Bondet","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Translational Immunology Unit Universit\u00e9 Paris\u2010Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darragh","family":"Duffy","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Translational Immunology Unit Universit\u00e9 Paris\u2010Cit\u00e9  Paris 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