D1.434 - Phenotyping Common Variable Immunodeficiency by Immune Dysregulation at Diagnosis: A Descriptive Comparison of Baseline Clinical and Laboratory Findings

Common variable immunodeficiency (CVID) is a heterogeneous antibody deficiency associated with infectious and noninfectious complications. Infection history guides clinical assessment, but its relationship with routine immunological markers and immune dysregulation at diagnosis remains unclear.  To evaluate clinical and immunological characteristics between CVID patients with and without immune dysregulation at diagnosis. Immunological markers independently associated with immune dysregulation were further evaluated.

In this single-centre retrospective cohort, 85 adults fulfilling the 2019 European Society for Immunodeficiencies (ESID) criteria for CVID were classified at diagnosis as immune-dysregulation–dominant (CVIDid) infection-only (CVIDio). Infection burden, serum immunoglobulins, and lymphocyte subsets were compared. Logistic regression evaluated associations with CVIDid.

At diagnosis, immune dysregulation was identified in 34 of 85 patients (40%). Median infection frequency was 0 episodes (IQR 0–4) in the CVIDid group and 5 episodes (IQR 4–7) in the group (p < 0.001). CVIDid cases showed greater alterations in switched memory B-cell percentages, CD4⁺ T-cell counts, and serum IgA. In multivariable analysis, reduced switched memory B-cell and CD4⁺ T-cell percentages, together with lower serum IgA levels, were independently associated with immune dysregulation. (OR: 0.59, 95% CI: 0.36–0.94; p = 0.035, OR: 0.86, 95% CI 0.77–0.96; p = 0.009, OR 0.26, 95% CI 0.08–0.82; p = 0.022).

Immune-dysregulation phenotypes were associated with fewer recent infections and more pronounced abnormalities in simple, widely available immunological markers. Combining infection burden with these parameters may help guide awareness and closer clinical monitoring of selected CVID profiles.