Clinical relevance of high-mobility group box protein 1 (HMGB1) in sickle cell disease : An Egyptian study / Aya Mohamed Adel Arafat ; Supervised Shahira Amin Zayed , Shahira Kamal Anis Botros , Mohamed Ahmed Fateen

Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Although the molecular origin of the Sickle cell disease (SCD) is clear, the medical treatment for the specific complications is not yet available (Zhang et al., 2016). During tissue injury, High mobility group box 1 (HMGB1) is passively released from necrotic cells and actively secreted by inflammatory cells. Extracellular HMGB1 acts as an amplifier of Toll-Like Receptor (TLR)-dependent inflammation rather than a primary trigger of inflammation (Bianchi et., 2017). Objectives: This study aimed at studying HMGB1 quantitative trait locus reference sequence 2249825 (rs2249825) and its serum level in SCD patients and healthy subjects to explore its possible role in the pathogenesis of vaso-occlusive crises (VOCs). Methods: HMGB1 rs2249825 was assayed in peripheral blood samples using real-time polymerase chain reaction (PCR). While the serum level was assayed using a two-site enzyme-linked immunosorbent technique (ELISA). Results: Both the SCD patients and the control group had comparable HMGB1 rs2249825 genotype frequencies (P-value >0.05). SCD patients at their steady-state showed a statistically significantly higher serum HMGB1 levels than the healthy control, a median of 0.6 with a range of 0.1- 85 nanogram/ milliliter (ng/ml) versus a median of 0.3 and a range of 0.1-3 ng/ml (P-value <0.001). Statistically significant skewed high serum HMGB1 in the VOC samples in contrast to the steady-state sample was observed in the SCD patients with a median 3.2 ng/ml and a range of 0.3-76.4 ng/ml versus a median of 0.2 and a range 0.2-7.4 ng/ml (P-value <0.0001)

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