Publication Date
1-26-2026
Journal
bioRxiv
DOI
10.64898/2026.01.15.698722
PMID
41607518
PMCID
PMC12836332
PubMedCentral® Posted Date
1-26-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
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 CD27 variants have been reported. Here, we describe three patients from two unrelated families, homozygous for a novel loss-of-function (LOF) CD27 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 CD27 variant causing autosomal recessive (AR) CD27 deficiency, characterized by a unified susceptibility to EBV yet variable clinical manifestations, ranging from chronic viremia to malignancy.
Published Open-Access
yes
Recommended Citation
Yang, Rui; Turunbedu, Solomon K; Nandiwada, Sara; et al., "Distinct EBV-Associated Phenotypes Due to a Novel Homozygous Missense Variant in CD27" (2026). Faculty, Staff and Students Publications. 7947.
https://digitalcommons.library.tmc.edu/baylor_docs/7947