Cytokine Dependent Hematopoietic Cell Linker (CLNK) is Highly Elevated in Blood Transfusion Dependent Beta-Thalassemia Major Patients - 13/01/21

Doi : 10.1016/j.tracli.2021.01.003

Hussein Kadhem Al-Hakeim ^a,^⁎ , Hawraa Hussein Al-Mayali ^b, Shatha Rouf Moustafa ^c, Michael Maes ^d,^e,^f
^a Professor in Medical Chemistry, Department of Chemistry, College of Science, University of Kufa, Iraq
^b MSc in Biochemistry, Department of Chemistry, College of Science, University of Kufa, Iraq
^c Clinical Analysis Department, College of Pharmacy, Hawler Medical University, Havalan City, Erbil, Iraq
^d Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
^e Department of Psychiatry, Medical University Plovdiv, Plovdiv, Bulgaria
^f IMPACT Research Center, Deakin University, Geelong, Australia

^⁎Corresponding author. Professor in Medical Chemistry, Department of Chemistry, College of Science, University of Kufa -Iraq. Tel.: ++9647811345471.Professor in Medical Chemistry, Department of Chemistry, College of Science, University of Kufa -Iraq. Tel.: ++9647811345471

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Abstract

Background

Transfusion-dependent β-thalassemia (TDT) is a severe form of thalassemia caused by mutations in the β-globin gene, resulting in partial or complete deficiency of β-globin chains. This deficiency results in oxidative stress, dyserythropoiesis, and chronic anemia. Cytokine-dependent hematopoietic cell linker (CLNK) belongs to adaptor proteins that have the capacity to interact with multiple signaling proteins and function in the organization of the molecular components required for signal transduction.

Objectives

This is the first study which measured serum CLNK in TDT patients and examines the correlation between CLNK and iron overload biomarkers.

Patients and methods

Sixty children with TDT and 30 normal children (aged 3-12 years old) participated in the present study. The patients were on blood transfusion as a part of their treatment regimen. Serum C-reactive protein was negative in all samples.

Results

The results showed significantly higher (p<0.001) serum CLNK levels in TDT patients as compared with controls. The TDT diagnosis explained 19.4% of the variance in CLNK levels.

The increased levels of CLNK were significantly associated with indicants of iron overload, namely increased ferritin levels.

Conclusions

Increased CLNK levels in TDT may be explained by reciprocal effects between immune signaling and immature erythrocytes, which release soluble receptors and signaling molecules, including CLNK, in the blood.

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Keywords : CLNK, Cytokines, Inflammation, Thalassemia, Ferritin, Iron overload