Abstract
Serum free light chains (sFLCs) have recently been introduced as a diagnostic biomarker in common variable immunodeficiency (CVID) patients. Most patients with CVID have undetectable or lower levels of sFLCs compared to people with other types of immune system deficiencies with hypogammaglobulinemia, except for patients with agammaglobulinemia (AGG). Decreased production of kappa (κ) and lambda (λ) light chains over immunoglobulins (Ig) suggests a malfunction in early B cell development or plasma cell dysfunction may cause CVID. In this cross-sectional study, immunoturbidimetry was used to measure sFLCs in 70 immunodeficiency patients, including 39 patients with CVID, 31 patients with other immunodeficiencies with hypogammaglobulinemia such as combined immunodeficiency (CID), AGG, and other primary immunodeficiencies (PIDs), and 20 healthy controls. The levels of both κ and λ chains were significantly higher in patients with CID than patients with CVID and AGG patients (p < 0.05). The median (Q1–Q3) κ level in patients with other primary immunodeficiency disorders (PIDs) was significantly higher than that observed in patients with AGG and CVID (p < 0.01). Similarly, the median (Q1–Q3) λ level was higher in patients with other PIDs compared with those with AGG and CVID (p < 0.05).ROC analysis of κ and λ disclosed an area under the curve (AUC) for κ was 0.98 (95% CI: 0.96–0.99, p < 0.0001) and for λ was 0.95 (95% CI: 0.89–0.99, p < 0.0001) in patients with CVID. The sFLCs test can help distinguish between CVID and other immunodeficiency patients with hypogammaglobulinemia and the diagnosis of hypogammaglobulinemia. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-41057-6.