{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:51:43Z","timestamp":1781639503853,"version":"3.54.5"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We present a case of disseminated granulomatous disease associated with live attenuated vaccine-derived rubella virus (VDRV) in an immunodeficient patient who subsequently developed fatal multi-organ failure, including neurological deficits, with VDRV detected in the cerebrospinal fluid. Posthumous genetic analysis found a heterozygous missense mutation in\n                    <jats:italic>IKZF3<\/jats:italic>\n                    , a gene where haploinsufficiency is linked to immunodeficiency and immune dysregulation. Functional studies demonstrated that this mutation decreases AIOLOS protein stability and half-life, and family members carrying the same mutation exhibited decreased AIOLOS levels. This report underscores the importance of considering persistent rubella virus (RuV) infection in patients with cutaneous granulomatous lesions and highlights the need for comprehensive evaluation to uncover potential underlying immunodeficiencies, which could inform and optimize individualized treatment strategies.\n                  <\/jats:p>","DOI":"10.1007\/s10875-026-01990-7","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:54:16Z","timestamp":1772085256000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Fatal Systemic Granulomatous Disease Associated with Vaccine-Derived Rubella Virus in AIOLOS-Associated Immunodeficiency"],"prefix":"10.1007","volume":"46","author":[{"given":"Linda","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Sun","family":"Kuehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayna","family":"Gager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin A. Gil","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila M.","family":"Perelygina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LiJuan","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-hsin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Niemela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Stoddard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Helm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolyn","family":"Wanat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galen","family":"Foulke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Leung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio D.","family":"Rosenzweig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misha","family":"Rosenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"issue":"1","key":"1990_CR1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.jaci.2021.05.007.","volume":"149","author":"M Gro\u00df","year":"2022","unstructured":"Gro\u00df M, Speckmann C, May A, Gajardo-Carrasco T, Wustrau K, Maier SL, et al. Rubella vaccine-induced granulomas are a novel phenotype with incomplete penetrance of genetic defects in cytotoxicity. J Allergy Clin Immunol. 2022;149(1):388-399.e4. https:\/\/doi.org\/10.1016\/j.jaci.2021.05.007.","journal-title":"J Allergy Clin Immunol"},{"key":"1990_CR2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2025.110469","volume":"274","author":"N Klangkalya","year":"2025","unstructured":"Klangkalya N, Esteve-Sole A, Gil Silva AA, Stoddard JL, Niemela JE, Prader S, et al. Ikaros protein stability is regulated by its early N-terminal region and C-terminal dimerization domain. Clin Immunol. 2025;274:11046910.1016\/j.clim.2025.110469.","journal-title":"Clin Immunol"},{"issue":"12","key":"1990_CR3","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211118","volume":"218","author":"HS Kuehn","year":"2021","unstructured":"Kuehn HS, Chang J, Yamashita M, Niemela JE, Zou C, Okuyama K, et al. T and B cell abnormalities, pneumocystis pneumonia, and chronic lymphocytic leukemia associated with an AIOLOS defect in patients. J Exp Med. 2021;218(12):e20211118. https:\/\/doi.org\/10.1084\/jem.20211118.","journal-title":"J Exp Med"},{"issue":"3","key":"1990_CR4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI172573","volume":"134","author":"HS Kuehn","year":"2024","unstructured":"Kuehn HS, Sakovich IS, Niemela JE, Gil Silva AA, Stoddard JL, Polyakova EA, et al. Disease-associated AIOLOS variants lead to immune deficiency\/dysregulation by haploinsufficiency and redefine AIOLOS functional domains. J Clin Invest. 2024;134(3):e172573. https:\/\/doi.org\/10.1172\/JCI172573.","journal-title":"J Clin Invest"},{"issue":"6","key":"1990_CR5","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1001\/jamadermatol.2022.0055","volume":"158","author":"LD Notarangelo","year":"2022","unstructured":"Notarangelo LD. Rubella virus\u2013associated granulomas in immunocompetent adults\u2014possible implications. JAMA Dermatol. 2022;158(6):611\u20133. https:\/\/doi.org\/10.1001\/jamadermatol.2022.0055.","journal-title":"JAMA Dermatol"},{"issue":"3","key":"1990_CR6","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/j.iac.2020.04.004","volume":"40","author":"CJ Nunes-Santos","year":"2020","unstructured":"Nunes-Santos CJ, Kuehn HS, Rosenzweig SD. IKAROS family zinc finger 1\u2013associated diseases in primary immunodeficiency patients. Immunol Allergy Clin North Am. 2020;40(3):461\u201370. https:\/\/doi.org\/10.1016\/j.iac.2020.04.004.","journal-title":"Immunol Allergy Clin North Am"},{"issue":"10","key":"1990_CR7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008080.","volume":"15","author":"L Perelygina","year":"2019","unstructured":"Perelygina L, Chen MH, Suppiah S, Adebayo A, Abernathy E, Dorsey M, et al. Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies. PLoS Pathog. 2019;15(10):e1008080. https:\/\/doi.org\/10.1371\/journal.ppat.1008080.","journal-title":"PLoS Pathog"},{"issue":"7","key":"1990_CR8","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1001\/jamadermatol.2021.1577","volume":"157","author":"BE Shields","year":"2021","unstructured":"Shields BE, Perelygina L, Samimi S, Haun P, Leung T, Abernathy E, et al. Granulomatous dermatitis associated with rubella virus infection in an adult with immunodeficiency. JAMA Dermatol. 2021;157(7):842\u20137. https:\/\/doi.org\/10.1001\/jamadermatol.2021.1577.","journal-title":"JAMA Dermatol"},{"issue":"7","key":"1990_CR9","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1038\/s41590-021-00951-z","volume":"22","author":"M Yamashita","year":"2021","unstructured":"Yamashita M, Kuehn HS, Okuyama K, Okada S, Inoue Y, Mitsuiki N, et al. A variant in human AIOLOS impairs adaptive immunity by interfering with IKAROS. Nat Immunol. 2021;22(7):893\u2013903. https:\/\/doi.org\/10.1038\/s41590-021-00951-z.","journal-title":"Nat Immunol"},{"key":"1990_CR10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.866582","volume":"13","author":"M Yamashita","year":"2022","unstructured":"Yamashita M, Morio T. AIOLOS variants causing immunodeficiency in human and mice. Front Immunol. 2022;13:866582. https:\/\/doi.org\/10.3389\/fimmu.2022.866582.","journal-title":"Front Immunol"},{"issue":"6","key":"1990_CR11","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1001\/jamadermatol.2022.0828","volume":"158","author":"KA Wanat","year":"2022","unstructured":"Wanat KA, Perelygina L, Chen MH, Hao L, Abernathy E, Bender NR, et al. Association of persistent rubella virus with idiopathic skin granulomas in clinically immunocompetent adults. JAMA Dermatol. 2022;158(6):626\u201333. https:\/\/doi.org\/10.1001\/jamadermatol.2022.0828.","journal-title":"JAMA Dermatol"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-026-01990-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-026-01990-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-026-01990-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:54:19Z","timestamp":1781636059000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-026-01990-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1990"],"URL":"https:\/\/doi.org\/10.1007\/s10875-026-01990-7","relation":{},"ISSN":["1573-2592"],"issn-type":[{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]},"assertion":[{"value":"23 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors affirm that the family of the patient described provided informed consent for publication of the images in Fig.\u00a0\n                      \n                      .","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"28"}}