Distinct EBV-Associated Phenotypes Due to a Novel Homozygous Missense Variant in CD27

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• CD27 and CD70 are crucial for anti-Epstein-Barr virus (EBV) immunity.
• Biallelic deficiencies in CD27/CD70 signaling lead to EBV susceptibility.
• Sixteen pathogenic CD27 variants are previously reported.

Purpose of the Study:

• To characterize a novel CD27 loss-of-function (LOF) variant.
• To investigate the clinical and functional consequences of this variant.

Main Methods:

• Genetic analysis of patients from two families.
• Functional studies of the novel CD27 variant (S70P).
• Clinical evaluation of patient phenotypes.

Main Results:

• Identified three patients homozygous for a novel CD27 S70P variant.
• Patients presented with EBV viremia, lymphoproliferative disease, and variable immune issues.
• S70P variant demonstrated impaired CD27 surface expression and abolished CD70 binding, confirming complete LOF.

Conclusions:

• The S70P variant represents a novel cause of autosomal recessive (AR) CD27 deficiency.
• AR CD27 deficiency confers susceptibility to EBV, ranging from chronic viremia to Hodgkin lymphoma.