CVID-Associated Enteropathy: Clinical, Biochemical, and Genetic Insights from a Single-Center Cohort
Jelena Ljubicic, Ivan Rankovic, Uros Karic, Rada Miskovic, Branka Bonaci-Nikolic, Ana Petkovic, Maja StojanovicIntroduction
Enteropathy represents one of the most frequent noninfectious clinical manifestations of common variable immunodeficiency (CVID), with underlying pathophysiological mechanisms that remain insufficiently understood. Patients with CVID-associated enteropathy (CVID-E) have a significantly higher frequency of liver involvement and malignancies, both contributing to disease-related complications and increased mortality. The aim of this study was to comprehensively characterize the clinical, biochemical, and genetic features of patients with CVID-E.
Material and Methods
Between January 2020 and December 2025, 57 patients with CVID were followed at the Clinic of Allergy and Immunology, University Clinical Center of Serbia. During routine follow-up, 28 (49.1%) patients reported symptoms suggestive of an enteropathic phenotype, including chronic diarrhea, abdominal pain, loss of appetite, and unintended weight loss. Only patients who underwent a complete diagnostic work-up, including radiologic, microbiological, and laboratory investigations, were included in our study.
Results
Gluten-sensitive–like enteropathy was the most common endoscopic and histopathological finding (52.9%), followed by inflammatory bowel disease-like colopathy (23.5%) and nodular lymphoid hyperplasia (17.6%). Patients with CVID-E exhibited elevated fecal calprotectin levels (median 185 µg/g; interquartile range [IQR] 103–1,000 µg/g). When compared with non-enteropathic CVID patients, those with CVID-E had significantly lower serum IgA levels (median 0.01 vs. 0.025 g/L, p < 0.05), albumin (average 41 vs. 46 g/L, p = 0.03), and HDL (median 0.7 vs. 1.09 mmol/L, p = 0.02) and higher levels of alkaline phosphatase (median 102 vs. 79I U/L, p = 0.03). Following CVID diagnosis, 21.34% of patients developed malignancies, of which 50% were localized in the gastrointestinal tract. In three patients, variants with potential relevance to CVID-E were identified in IRF2BP2, IFNGR1, and PIK3CG genes.
Conclusion
CVID-E represents a clinically significant phenotype marked by characteristic biochemical alterations, increased malignancy risk, and potential genetic predisposition. Therefore, comprehensive radiologic, histopathological, and microbiological evaluation and genetic testing are essential to ensure early complication detection and enable prompt, intensive management.