Implications of baseline IgG4-to-IgG ratios for autoimmune manifestations in common variable immunodeficiency

Aims: This study investigated whether baseline serum IgG4-to-IgG ratios are associated with the presence of autoimmune manifestations in patients diagnosed with common variable immunodeficiency (CVID). Methods: A retrospective cohort analysis was performed using clinical data from 85 patients with CVID evaluated between January 2013 and November 2023. The study included patients aged 18 years and over with a confirmed diagnosis of CVID. Patients with incomplete or insufficient clinical information were excluded. Serum IgG4-to-IgG ratios measured at initial assessment were compared between individuals with autoimmune manifestations and those without. Results: Of the 85 patients, 36 (42.4%) had at least one autoimmune condition. Autoimmune cytopenias constituted the most frequent autoimmune presentation (17.6%). The median IgG4-to-IgG ratio in CVID with autoimmune disease was 0.018 (interquartile range, 0.014–0.043), which was significantly lower than that observed in the group without autoimmunity (p=0.03). Building on this finding, ROC analysis identified a threshold IgG4-to-IgG ratio of 0.04 for differentiating autoimmune from non autoimmune cases (AUC 0.709; 95% CI 0.60–0.82; p=0.002; sensitivity 72%; specificity 60%). Finally, logistic regression analysis demonstrated that a reduced IgG4-to-IgG ratio was significantly associated with the development of autoimmune disease (odds ratio, 1.682; 95% confidence interval, 1.129–2.489; p=0.037). Conclusion: Lower baseline IgG4-to-IgG ratios were associated with autoimmune manifestations in CVID. This parameter may serve as a practical adjunctive biomarker for the early identification and monitoring of autoimmune complications in this heterogeneous disorder.