Clinical and immunological heterogeneity in common variable immunodeficiency: a cluster analysis of a single-center cohort

Abstract

Common variable immunodeficiency (CVID) presents with diverse clinical and immunological manifestations. This study aimed to investigate the relationships between clinical phenotypes and immunological profiles in an adult CVID cohort. We retrospectively evaluated demographic and clinical features, infectious/non-infectious complications, immunological parameters, and flow cytometric findings in 32 adult patients (aged ≥ 18 years; 14 female, 18 male) diagnosed with CVID. Based on clinical phenotypes and organ system involvement, three clusters were identified: Cluster 1 (n = 10, 31.2%) was characterized by dominant infectious phenotype; Cluster 2 (n = 8, 25.0%) featured infectious manifestations but lacked lymphoproliferation; allergic conditions were relatively more common; and Cluster 3 (n = 14, 43.8%) was distinguished by dominant autoimmune features and lymphoproliferation. The most frequently observed cluster in our patient cohort was Cluster 3. The most significant predictors in the clustering analysis were lymphoproliferation, autoimmunity, and infection. The percentage of CD4+CD45RO+ cells was significantly higher in patients without infections, whereas the percentage of CD8+CD45RO+ cells was higher in those with infections (p = 0.007 and 0.003, respectively). Among patients with autoimmunity, CD8+CD45RO+ percentages were lower and CD21lowCD38low B cell populations were higher compared to those without autoimmunity (p = 0.005 and p = 0.047, respectively). This study highlights infection, autoimmunity, and lymphoproliferation as prominent phenotypic features in CVID and reveals distinct immune cell profiles among these phenotypes. These findings may provide valuable guidance for improving diagnostic processes and patient management in CVID.