IGHG4: innovative diagnostic biomarkers for iron overload in β-thalassemia patients.

Objectives: This study aims to investigate the serotransferrin (TF), complement C1s subcomponent (C1S), immunoglobulin heavy constant gamma 4 (IGHG4), hemoglobin subunit alpha (HBA1), and clusterin (CLU) contents in β-thalassemia patients, and explores their physiological role as potential non-invasive bioindicators for disease diagnosis and iron overload.

Methods: A total of 62 children with β-thalassemia were recruited and categorized by genotype, along with 17 healthy pediatric volunteers for analysis. The circulating ferritin content was evaluated, and plasma levels of TF, C1S, IGHG4, HBA1, and CLU were assessed using ELISA. The primary outcome of this study was the correlation between the five protein marker levels and iron overload. Continuous variables were analyzed using the Student's t-test or the Mann-Whitney U test. A binary logistic regression model identified independent predictors of iron overload in patients with β-thalassemia. Receiver operating characteristics (ROC) were employed to evaluate the model's performance.

Results: The IGHG4 protein content was significantly lower in β-thalassemia patients compared to healthy controls. The IGHG4 protein content was reduced in the β⁺/β⁰ and β⁰/β⁰ patient populations compared to controls, with no significant difference observed between the β⁺/β⁰ group and healthy controls. A strong inverse relationship was identified between the IGHG4 protein content and SF concentration (r = -0.322, p = 0.004). Finally, plasma IGHG4 levels demonstrated adequate diagnostic capability, as indicated by our ROC curve analysis.

Conclusion: In conclusion, decreased IGHG4 protein levels are significantly associated with the degree of iron overload in β-thalassemia patients and may serve as a possible biomarker for evaluating iron overload.