Inflammatory Cytokine Dysregulation and Interleukin Gene Polymorphisms in Iraqi Pediatric Sickle Cell Anemia: Implications for Genetic Risk Stratification and Targeted Therapy.

BACKGROUND

Sickle cell anemia (SCA) involves inflammation that worsens disease symptoms and complications. The inflammatory profiles and genetic determinants among the pediatric Iraqi population are not well described. The current study aimed to analyze pediatric SCA in Iraq for cytokine dysregulation and interleukin gene polymorphism.

PROCEDURE: A case-control study was performed involving 216 pediatric SCA patients and 330 healthy controls. Serum levels of six interleukins (IL-1β, IL-2, IL-4, IL-8, IL-10, and IL-17) were quantified using the ELISA technique; the gene polymorphisms for the interleukin (IL-1β -511 C/T, IL-2 -330 T/G, IL-4 -590 C/T, IL-8 -251 A/T, IL-10 -1082 G/A, IL-17 -197 G/A).

RESULTS

Both the IL-10 -1082 G/A and IL-17 -197 G/A polymorphisms were independently and significantly associated with SCA disease status. Carriers of the IL-10 -1082 A allele (AA genotype: OR = 2.11, 95% CI: 1.58-2.82, p<0.001) and the IL-17 -197 A allele (AA genotype: OR = 2.02, 95% CI: 1.49-2.74, p<0.001) were significantly more frequent among SCA patients compared to healthy controls. There was a marked increase in the gene-dose effect on the production of the described cytokines. There was a noteworthy association of IL-17 levels with the frequency of vaso-occlusive crises (r = 0.623, p <0.001). The diagnostic value of IL-8 (AUC = 0.958) and IL-17 (AUC = 0.946) was excellent according to the ROC curve.

CONCLUSIONS

There is evidence of significant inflammatory dysregulation and genetic associations in pediatric patients with SCA in Iraq. There is a clear justification for developing anti-inflammatory therapies, and further evidence to support the role of cytokines as biomarkers of Sickle cell anemia (SCA).