{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:04Z","timestamp":1785430444153,"version":"3.56.0"},"posted":{"date-parts":[[2026,1,15]]},"group-title":"Immunology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["P50 CA126752"],"award-info":[{"award-number":["P50 CA126752"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Biallelic deficiencies of CD27 and its ligand CD70 underlie selective susceptibility to Epstein-Barr virus (EBV) infection and its acute and chronic complications, underscoring their non-redundant roles in anti-EBV immunity. To date, 16 pathogenic\n                  <jats:italic>CD27<\/jats:italic>\n                  variants have been reported. Here, we describe three patients from two unrelated families, homozygous for a novel loss-of-function (LOF)\n                  <jats:italic>CD27<\/jats:italic>\n                  variant, resulting in substitution of serine 70 with proline (S70P). All three patients presented with EBV viremia and lymphoproliferative disease, with variable immune dysregulation or recurrent otosinopulmonary infections. One patient developed EBV-associated Hodgkin lymphoma. Functional studies demonstrated that the S70P variant impaired surface expression of CD27 and abolished CD70 binding, rendering complete LOF. Together, S70P represents a novel pathogenic\n                  <jats:italic>CD27<\/jats:italic>\n                  variant causing autosomal recessive (AR) CD27 deficiency, characterized by a unified susceptibility to EBV yet variable clinical manifestations, ranging from chronic viremia to malignancy.\n                <\/jats:p>","DOI":"10.64898\/2026.01.15.698722","type":"posted-content","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:20:20Z","timestamp":1768533620000},"source":"Crossref","is-referenced-by-count":0,"title":["Distinct EBV-Associated Phenotypes Due to a Novel Homozygous Missense Variant in\n                  <i>CD27<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4427-2158","authenticated-orcid":false,"given":"Rui","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"},{"name":"William T. Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon K.","family":"Turunbedu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Nandiwada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choladda V.","family":"Curry","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek M.","family":"Elghetany","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Baylor College of Medicine, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooks P.","family":"Scull","sequence":"additional","affiliation":[{"name":"Texas Children\u2019s Cancer Center, Department of Pediatrics, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junnan","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"},{"name":"William T. Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Vargas-Hernandez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"},{"name":"William T. Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan K.","family":"Chinn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"},{"name":"William T. Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"},{"name":"William T. Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl E.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"},{"name":"Texas Children\u2019s Cancer Center, Department of Pediatrics, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX, USA"},{"name":"Texas Children\u2019s Cancer and Hematology Centers Global HOPE (Hematology-Oncology Pediatric Excellence) Program, Texas Children\u2019s Hospital, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Forbes","family":"Satter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA"},{"name":"William T. Shearer Center for Human Immunobiology, Texas Children\u2019s Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020606233094000_2026.01.15.698722v2.1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1529-8817.2004.00091.x"},{"key":"2026020606233094000_2026.01.15.698722v2.2","doi-asserted-by":"crossref","unstructured":"Adzhubei, I. , D.M. Jordan , and S.R. Sunyaev . 2013. Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 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