Growth differentiation factor 15 in common variable immunodeficiency patients: Diagnostic value and prediction of autoimmunity risk

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Background: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by heterogeneous clinical phenotypes, frequently accompanied by autoimmune complications. Beyond recurrent infections, autoimmunity represents a major cause of morbidity and mortality. Early diagnosis and treatment of autoimmune manifestations are of vital importance. Objective: This study aimed to determine the diagnostic value of serum growth differentiation factor 15 (GDF15) levels in patients with CVID and to investigate its potential as a biomarker for predicting autoimmune complications. Methods: This prospective, cross-sectional study included 80 patients with a diagnosis of CVID who were followed up and 40 age- and sex-matched healthy controls. The patients with CVID were divided into two subgroups based on the presence of concomitant autoimmune disease (autoimmunity present, n = 42; absent, n = 38). GDF15 levels were measured by using the enzyme-linked immunosorbent assay (ELISA) method. The diagnostic performance of GDF15 was evaluated by receiver operating characteristic analysis, and its impact on the development of autoimmunity was assessed by using multivariate logistic regression analysis. Results: GDF15 levels were found to be significantly higher in the CVID group with autoimmune disease (median, 2205 pg/mL) compared with both the CVID group without autoimmunity (1526 pg/mL) and the healthy control group (1083 pg/mL) (p < 0.001). A negative correlation was observed between GDF15 levels and serum immunoglobulin G (IgG), IgM, and IgA levels (r = −0.38, p < 0.001; r = −0.299, p = 0.001; r = −0.236, p = 0.01, respectively). In the receiver operating characteristic analysis, the area under the curve value for GDF15 in the diagnosis of CVID was 0.769, and was 0.683 for predicting the presence of autoimmunity. Multivariate logistic regression analysis revealed that elevated GDF15 levels (>1564 pg/mL) independently increased the risk of developing autoimmunity in patients with CVID by 5.1-fold (odds ratio 5.164 [95% confidence interval, 1.386‐19.241]; p = 0.014). Conclusion: To our knowledge, this study was the first to demonstrate that GDF15 levels are elevated in patients with CVID and that this elevation is associated with autoimmune complications. GDF15 is a potential biomarker that can be used for determining the risk of autoimmunity and monitoring patients at high risk in the CVID.

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