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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Th1/Th2 cytokine imbalance with novel IL-17F elevation in Iraqi transfusion-dependent beta-thalassemia: a
Suzan Sabbar Mutlag1, Ghaith A Al-Tameemi2, Mohammed Abdul-Mounther Othman3
1Department of Pediatrics, College of Medicine, University of Al-Qadisiyah, Diwaniyah, Iraq.
Background:
Beta-thalassemia (β-Thal) is an inherited hemoglobin disorder caused by defective β-globin synthesis, resulting in ineffective erythropoiesis, chronic hemolytic anemia, and altered iron metabolism; it is highly prevalent in Iraq, a country with a complex and not fully characterized immunological profile. Inflammatory cytokine dysregulation in transfusion-dependent patients further compromises hematopoiesis, drives progressive iron overload, and perpetuates immune activation. This study aims to compare the gene expression and protein levels of seven cytokines - IL-1β, IL-4, IL-5, IL-12, IL-13, IL-17F, and TNF-α - between patients with beta-thalassemia and healthy controls.
Methods:
This case study included 344 patients with beta-thalassemia and 440 healthy patients of the same age and gender that were collected from Maysan (Al-Amarah) and Najaf, Iraq. The mRNA expression levels were assessed using quantitative real time polymerase chain reaction (qPCR) and included GAPDH as the internal reference gene for all assessments done. The levels of cytokines present in the serum were determined using ELISA method. The statistical tests that were included are: independent samples t-test, Pearson correlation, receiver operating characteristic (ROC) curve, and binary logistic regression.
Results:
For all of the patients that showed the presence of IL-1β, there was a significant elevation in the mRNA and serum protein levels of IL-12, IL-17F, and TNF-α. The results showed a decrease in the presence of IL-4, IL-5, and IL-13. For all patients, TNF- α showed the greatest ability to diagnose a case of beta-thalassemia (AUC = 0.961). There was a significant positive correlation with serum ferritin, the number of blood transfusions, and splenomegaly.
Conclusions:
Pro-inflammatory cytokines TNF-α and IL-1β demonstrated the strongest positive correlations with serum ferritin (r = 0.798 and r = 0.714, respectively), transfusion frequency, and splenomegaly. Conversely, Th2 cytokines IL-4 and IL-13 showed significant inverse correlations with ferritin and positive correlations with hemoglobin, reflecting progressive Th2 suppression with increasing disease burden.