Abstract The study’s goal is to appraise the immunological inflammatory marker Trefoil Factor 3, which interacts with thalassemia pathogenesis particularly following splenectomy, and may offer new therapy options for the illness and its repercussions. This is a case-control study design that included 60 patients identified as β-thalassemia major as participators in this study, in addition to 30 seemingly healthy subjects with age and sex close to the patients group who served as a control group. The participants were distributed into four groups: control group, splenectomized patients, non-splenectomized patients, and total patients. Suitable statistical techniques were employed to investigate the results. The study’s findings demonstrated that there was a significance increase in the serum levels of TFF3 when comparing between (splenectomized, non-splenectomized and total patients) with healthy group (322.16±51.241, p-value=0.01, 317.20±42.449, p-value=0.01, 320±46.6, p-value=0.01), vs (309.38±21.94), respectively. Moreover, a comparison between splenectomized and non-splenectomized showed a significantly decrease in TFF3 (322.16±51.241) vs (317.20±42.449), (p-value=0.043).The presented study also revealed significant positive correlation between TFF3 level with ferritin, iron, total iron binding capacity, transferrin saturation, transferrin, fasting serum glucose, insulin and homeostasis model assessment-insulin resistance. Furthermore, unsaturated iron binding capacity and homeostasis model assessment-beta found a significant negative correlation with TFF3 level. High serum levels of TFF3 in beta thalassemia patients, especially in splenectomies patients, are downregulated by inflammatory cytokines, which are primarily regarded as traditional inflammatory cytokines and are related to insulin resistance. Hence, TFF3 level can serve as a potential predictive for the early detection of beta thalassemia in the development and progression of complications.
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