ABSTRACT
Sickle cell anaemia (SCA) is a chronic inflammatory condition associated with elevated inflammatory markers and marked leukocytosis. Previous studies have shown that sickle cell anaemia is clinically characterized by significant morbidity and mortality due to the Vaso-occlusive events, impaired leukocyte functions as well as increased susceptibility to infections.
Some mechanisms of leukocyte activation and functions and influence of the protein expressed by the TGF-ß1 gene on leukocyte functions were investigated in sickle cell anaemia subjects in their steady and crisis states. Ninety (90) participants comprising 24 HbAA, 22 HbAS, 23 steady state HbSS and 21 vaso-occlusive crisis state HbSS subjects respectively who were age and sex-matched were recruited for this study and classified into six groups viz haemoglobin AA subjects as Control group, haemoglobin AS Carrier subjects, haemoglobin SS subjects at Steady state, haemoglobin SS subjects in Vaso-occlusive crisis state, haemoglobin SS subjects on drugs/medications, and the haemoglobin SS subjects on drugs/medications and blood transfusion groups. The study was divided into four phases comprising the preliminary haematological analysis phase (I), leukocyte function assay phase (II), serum proinflammatory
cytokine and adhesion molecules assay phase (III), and the pro-inflammatory cytokines protein
expression of the Transforming growth factor-beta 1 gene (TGF-β1) assay phase (IV).
Haematological analysis, haemoglobin electrophoresis, foetal haemoglobin estimation, leukocyte functions assays, pro-inflammatory biomarkers, and adhesion molecules were assessed in line with the various phases. PCR restriction fragment length polymorphism technique was used to assess the pro-inflammatory cytokines protein expression of the
Transforming growth factor-beta 1 gene. The total leukocyte count of the SCA group was significantly elevated compared to the control and AS groups, while the monocyte count significantly increased in the SCA groups than the other groups (p<0.005, respectively).
However, the SCA groups had lower lymphocyte counts than the other groups (p<0.005, respectively). The platelet count of the SCA during crisis and on-drugs group was significantly elevated than the HbAS and control groups (p<0.005, respectively). There was also an elevated HbF concentration in the SCA groups compared to the HbAS and control groups (p<0.005, respectively). Leukocyte viability was significantly increased in the SCA groups than the other groups, while oxidative respiratory burst and phagocytic activities were significantly reduced in all the SCA groups when compared with the control and HbAS groups (p<0.005, respectively). Serum levels of the platelet factor 4, interleuken 8 and L-Selectin of the SCA groups were also significantly decreased when compared to the HbAS and control groups. Impaired polymorphonuclear cell response, reduced leukocyte phagocytic and oxidative respiratory burst activities coupled with dysregulated pro-inflammatory cytokines and leukocyte chemotactic factors are therefore possible mechanisms of altered leukocyte functions and infection susceptibility in sickle cell anaemia subjects.
