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Immunophenotyping markers and cell adhesion molecules in sickle cell anaemia patients in Saudi Arabia

Al-Najjar, Salwa Abdulrahman (2013) Immunophenotyping markers and cell adhesion molecules in sickle cell anaemia patients in Saudi Arabia. Doctoral thesis (PhD), Manchester Metropolitan University.

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Abstract

Sickle cell anaemia (SCA) is an autosomal recessive inherited haemoglobinopathy, characterized by chronic haemolysis and inflammation, frequent infections and recurrent vaso-occlusive crisis (VOC). The hallmark of VOC is severe acute pain due to ischaemic tissue injury. The resultant end organ damage contributes to the significant morbidity and mortality observed in this disease. Genetic and environmental interactions result in a variable phenotype. This study investigates the most common complications in SCA, including VOC and infections. Specifically, phagocytic activity of neutrophils and monocytes in the pathogenesis of SCA, and the most frequent bacterial infection. Furthermore, the study investigates changes in leukocytes subsets and the relationship between cell adhesion molecules expression and disease manifestations in patients during steady state and acute VOC. The results indicate that staphylococcus aureus is the most common organism isolated in SCA related infections, followed by Escherichia coli and Pseudomonas aeruginosa. There was no significant difference in phagocytic activity between both patient groups and control subjects. Lymphocyte subsets showed high percentages of total T lymphocytes, T helper and suppressor lymphocytes, B lymphocytes as well as NK cells in patients with SCA during steady state, while B lymphocytes and NK cells were significantly higher during acute VOC crisis, in comparison to control group. One of most important and novel findings of the present study in Saudi Arabia was the presence of high levels immunophenotypic expression of L-selectin on neutrophils, monocytes and lymphocytes during acute VOC in comparison to normal control subjects. Accordingly, as markers for leukocytes activation, L- selectin can be used as a predictor for VOC, which of value in the early diagnosis and intervention of these painful episodes. In addition another anoval finding, is the high levels of both soluble E- selectin (sE- selectin), soluble P- selectin (sP- selectin) markers were demonstrated in the serum of patients with SCA during both steady state and acute VOC. Levels of selectins were significantly higher in acute VOC. These findings suggest that patients with SCA have intact phagocytic activity and increased expression of adhesion molecules; L- selectin, E-selectin and P-selectin, which play an important role in the pathogensis of VOC. While sickle cell disease is a well-recognized state of chronic inflammation, the role of specific adhesion molecules should be further elucidated. Studies are needed to investigate the potential role of selectin antagonists, for prevention and reversal of acute vascular occlusions in SCA patients.

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