Clinical and immunological factors associated with gastrointestinal involvement in common variable immunodeficiency: a real-world study.

BACKGROUND

Gastrointestinal (GI) involvement is a common and clinically significant manifestation of common variable immunodeficiency (CVID); however, its relationship with immunological parameters remains incompletely understood.

OBJECTIVE

This study aimed to evaluate the association between GI involvement and immunological markers, particularly serum immunoglobulin levels and B-cell subsets, and to assess their discriminative performance.

METHODS

In this single-center retrospective study, 109 adult patients with CVID were included and categorized based on GI involvement. Clinical, endoscopic, histopathological, and immunological data were analyzed. Multivariable logistic regression analysis was performed to identify factors independently associated with GI involvement. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate discriminative performance.

RESULTS

GI involvement was present in 58.7% of patients. Patients with GI involvement had significantly lower serum IgA and IgM levels, as well as reduced percentages of CD19⁺CD27⁺IgD⁻ switched memory B cells. In multivariable analysis, low IgM levels (OR = 0.161, 95% CI: 0.041-0.633, p = 0.009) and decreased switched memory B-cell percentage (OR = 0.918, 95% CI: 0.855-0.986, p = 0.019) were independently associated with GI involvement. ROC analysis demonstrated good discriminative ability for serum IgM (AUC = 0.799, 95% CI: 0.708-0.889) and moderate discriminative performance for switched memory B cells (AUC = 0.695, 95% CI: 0.589-0.802). Endoscopic abnormalities were detected in 87.7% of evaluated patients, with inflammatory bowel disease-like patterns being the most common histopathological finding.

CONCLUSION

GI involvement is common in CVID and is independently associated with reduced IgM levels and decreased switched memory B cells, suggesting a potential role of impaired B-cell maturation in its pathophysiology. These findings may help identify patients at higher risk and support the clinical utility of immunophenotyping. Prospective multicenter studies are needed to validate these findings and to establish clinically relevant cutoff values.