Splenomegaly in CVID patients associates with CMV replication and alterations of immune cells and functions.

Publication date: Jul 04, 2025

Splenomegaly represents a frequent non-infectious manifestation in Common Variable Immunodeficiency (CVID) and associates with specific clinical and immunophenotypic characteristics. To investigate the association between splenomegaly, infections, and immunophenotype in CVID patients. A cohort of 32 CVID patients (13 with splenomegaly) was enrolled. Infectious workup encompassed a detailed medical history and data derived from routine diagnostic assessments including specific virological analysis of blood and stool samples, and QuantiFERON assay for tuberculosis. Immunophenotype was assessed by multiparametric flow cytometry. Statistical analyses were performed using Prism and Jamovi software. CMV viraemia was detected in 40% of splenomegalic CVID (sCVID) and was absent in non-sCVID patients. Of all infectious agents, CMV was the only one associated with splenomegaly (p=0. 009). The inclusion of CMV replication as a causative factor for splenomegaly in CVID is in line with the knowledge that splenomegaly is a hallmark of acute CMV infection and could help explain in the present CVID cohort 75% of otherwise unexplained splenomegalies. Flow cytometric analysis in sCVID vs. non-sCVID confirmed decreases in NK cell numbers and activation, in circulating inflammatory precursors (LinCD16), and increased T cell activation as defined by HLA-DR/CD69/CD38 expression. Splenomegaly in CVID patients may associate also with CMV replication. The combined identification in CMV sCVID of NK cell, inflammatory precursor and T cell imbalances suggests a possible combined cellular defect at precursor level in a subset of sCVID patients. When integrated into everyday clinical management, CMV viraemia could become a useful additional parameter for patient characterization and stratification.

Semantics

Original Article