• Surinder Safaya, Mohammed Alfarhan, Ahmed Sulaiman, Abdulla Alsulaiman, and Amein Al-Ali.
• Mohammed Bin Abdulrahman Al-Omran Scientific Chair for Hematological Diseases Prevalent in the Al-Ahsa Area, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia. Electronic address: ssafaya@kfu.edu.sa.
• Cytokine. 2019 Nov 1; 123: 154744.

BackgroundSickle cell anemia (SCA), a disorder with an important inflammatory component, where vasoocclusion is major contributor to the disease pathophysiology. Pro-inflammatory cytokines play an important regulatory role in the process of inflammation. We investigated the expression TL1A/DR3/DcR3 cytokine signaling pathway in peripheral blood mononuclear cells (PBMC) and their corresponding plasma levels in SCA subjects who presented with acute painful episodes.Materials And MethodsPBMC were isolated from the blood of SCA subjects and normal healthy controls. RNA isolated from PBMC was used for real time gene expression of TL1A/DR3/DcR3. Gene expression was compared in subgroups within SCA subjects with co-inherited fetal hemoglobin (HbF) or alpha-globin gene deletions. Plasma prepared from blood was used for determination of TL1A/DR3/DcR3 proteins by ELISA assays.ResultsIn the PBMC of SCA subjects, expression of TL1A and DcR3 is elevated, while DR3 expression is lowered in comparison to normal control PBMC. In SCA subjects with HbF > 10%, TL1A/DcR3 expression is lower, while HbF < 10% is associated with increased TL1A/DcR3 expression. Moreover, subjects with HbF > 10% appear to have significantly fewer pain episodes in comparison to those with HbF < 10%. Deletion of alpha-globin genes appears to have no significant effect on TL1A/DR3/DcR3 expression. Circulating levels of TL1A, DR3 and DcR3 in plasma were significantly elevated in SCA subjects.ConclusionsElevated TL1A and DcR3 expression in PBMC of SCA subjects during painful vasoocclusive crisis, suggest an altered TL1A expression may contribute to the pathophysiology of vasoocclusive crisis in SCA. HbF > 10% appears to moderate TL1A elevation, while HbF < 10% exacerbates TL1A/DcR3 responses. Furthermore, subjects with HbF > 10% have significantly lower pain episodes reported as compared to subjects with HbF < 10%.Copyright © 2019 Elsevier Ltd. All rights reserved.

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