D2.362 - Clinical and Immunological Characteristics of Non-Infectious Complications in Common Variable Immunodeficiency: A Single-Center Retrospective Evaluation in Adult Patients with CVID

Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency characterized not only by recurrent infections but also by non-infectious complications, which are major contributors to morbidity and mortality. This study aimed to evaluate the association between non-infectious complications and immunological markers in adult patients with CVID.

This study was designed as a single-center, retrospective analysis. Medical records of adult patients diagnosed with CVID were reviewed, and clinical characteristics together with laboratory parameters were evaluated. Patients were stratified based on malignancy, bronchiectasis, and immune dysregulation, the latter comprising autoimmunity, lymphoproliferation, and granulomatous disease. For each non-infectious complication, serum immunoglobulin levels (IgG, IgA, IgM, and IgE), lymphocyte subsets (CD3, CD4, CD8, CD19, and NK cells), and the CD4/CD8 ratio were compared.

A total of 78 adult patients with CVID were included in the analysis. Immune dysregulation was associated with significantly lower serum IgA levels, with median values of 14.5 mg/dL in patients with immune dysregulation compared to 28.6 mg/dL in those without (p = 0.05). Patients with an accompanying malignancy demonstrated significantly reduced lymphocyte subset percentages, including CD3 (87% vs. 79%; p = 0.028) and CD19 (2.95% vs. 7.6%; p = 0.008), compared with patients without malignancy. Similarly, the presence of lymphoproliferation (LPH) was associated with marked decreases in immunoglobulin levels. Patients with LPH exhibited significantly lower median IgA levels (10 vs. 30 mg/dL; p = 0.023) as well as substantially reduced IgE levels (0.9 vs. 4.77 IU/mL; p = 0.002). In contrast, no significant associations were identified between immunological parameters and the presence of autoimmunity, granulomatous disease, or bronchiectasis.

The findings of the present study suggest that immune dysregulation and lymphoproliferative disease in CVID tend to be accompanied by more pronounced hypogammaglobulinemia. In patients with malignancy, lower proportions of both T- and B-cell subsets were observed, which may reflect a more profound immune alteration in this subgroup. While these findings are consistent with previous observations implicating immune dysfunction in the development of malignancy in CVID, causal inferences cannot be drawn from the retrospective design of the study. The absence of significant associations with autoimmunity may be attributable to the heterogeneous nature of autoimmune manifestations in CVID and limited subgroup sizes. Overall, these findings suggest that routinely assessed laboratory parameters may support the clinical evaluation of non-infectious complications, while underscoring the need for larger prospective studies to clarify their prognostic relevance.