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Comparative study on biological factors influencing the development of alloimmunization in sickle cell disease patients in Ile-Ife, Nigeria
Author(s)
Aboderin, Florence Ifechukwude
Date Issued
2024
Type
Thesis
Abstract
Sickle cell disease (SCD) is a chronic haemolytic anaemia that remains a healthcare
challenge in Africa. Sickle haemoglobinopathies occur due to a mutation resulting in
the formation of an abnormal haemoglobin (Hb-S). In a reduced oxygen state
(deoxygenation), HbS polymerises, and the red cells become rigid and deformed,
assuming a sickle crescent shape. Blood transfusion remains the most common form
of therapy despite the risks. Patients with SCD have high levels of alloimmunization,
which may result in delayed haemolytic transfusion reactions. Research has
demonstrated an association between alloimmunization and SCD patients who have
received multiple blood transfusions. This study, therefore, aimed to investigate the
biological factors, including inflammatory, oxidative stress markers and the red cell
phenotype of SCD, in order to understand the mechanisms involved in the high rate
of alloimmunization. This study also assessed the dietary intake and nutrient adequacy
among young adults with SCD in Ile-Ife. To further establish that adequate nutrition
improves red blood cells and overall health outcomes.
We determined the dietary intake level, nutritional status, and demographic
characteristics among 50 young adults between 18 - 48 years and 50 age-matched
non-SCD as controls. Dietary data were obtained by 24-hour dietary recall. A food
frequency questionnaire was supplied to all participants, and body mass index (BMI)
results show that only about 23.7% of the participants met the required daily calorie
intake. In comparison, 76.3% of the participants did not meet the normal calorie
needed. Carbohydrates and proteins are major micronutrients that measured the
normal requirement by 93.8% and 54.6%, respectively. Minerals salts and vitamins
showed inadequate intake, especially retinol, beta carotene, folate, and vitamin D.
Fibre intake was insufficient, about 80.4%. The relationship between oxidative stress and inflammatory profiles was investigated in sickle cell patients who took blood
transfusions of two or more units. Results showed biochemical parameters such as
SOD, AST, ALT, Creatinine and Urea, with inflammatory markers such as CRP and
TNF being significantly increased (P = 0.003) in the test group compared to the control
group. Additionally, the results demonstrated a significant positive correlation (P< 0.05
r=) between CRP and IL-6, TNF and Catalase. However, there was a negative
correlation between AST, IL-β, SOD, Creatinine and Urea (P < 0.05 r=).
Haematological parameters, inflammatory markers and the incidence of
alloimmunization in both test and controls were determined. Red cell antibody typing
was determined by saline and anti-human globin (AHG) methods and was interpreted
using the ID panel profile. CRP, TNF, IL-1, IL-6, IL -1β were analysed using enzymelinked
immunosorbent assay (ELISA) technique. Full blood count (FBC) was
processed on an auto-analyser. The test group consisted of patients with SCD
confirmed with haemoglobin electrophoresis who had been transfused with at
least two pints of blood, while those in the control group were not SCD patients but
received the same units of blood. Results showed elevated alloimmunization in SCD
and significantly increased platelet counts compared to the control group. In addition,
the test group displayed evidence of inflammation with significantly increased levels
(P = 0.0001) of C-reactive protein and the pro-inflammatory cytokine TNF. This was
supported by a higher neutrophil count, which can also indicate elevated inflammation.
Furthermore, the pattern of antibodies detected in SCD was anti-Kell, JKa and Fya,
which was different from the control, which displayed anti-M and similarity with Kell
antibodies. There was, however, no significant correlation between inflammatory
markers and alloimmunization. In conclusion, this study shows that undernutrition and inadequate nutrients, if not
corrected, could result in high alloimmunization rates in SCD patients. High levels of
oxidative stress and inflammation also contribute to multidimensional factors liable for
elevated alloimmunization. In the management of SCD, it is imperative that nutritional
monitoring be encouraged alongside medical care to ensure adequate levels of macro
and micronutrients needed for maximum supply for body upkeep.
challenge in Africa. Sickle haemoglobinopathies occur due to a mutation resulting in
the formation of an abnormal haemoglobin (Hb-S). In a reduced oxygen state
(deoxygenation), HbS polymerises, and the red cells become rigid and deformed,
assuming a sickle crescent shape. Blood transfusion remains the most common form
of therapy despite the risks. Patients with SCD have high levels of alloimmunization,
which may result in delayed haemolytic transfusion reactions. Research has
demonstrated an association between alloimmunization and SCD patients who have
received multiple blood transfusions. This study, therefore, aimed to investigate the
biological factors, including inflammatory, oxidative stress markers and the red cell
phenotype of SCD, in order to understand the mechanisms involved in the high rate
of alloimmunization. This study also assessed the dietary intake and nutrient adequacy
among young adults with SCD in Ile-Ife. To further establish that adequate nutrition
improves red blood cells and overall health outcomes.
We determined the dietary intake level, nutritional status, and demographic
characteristics among 50 young adults between 18 - 48 years and 50 age-matched
non-SCD as controls. Dietary data were obtained by 24-hour dietary recall. A food
frequency questionnaire was supplied to all participants, and body mass index (BMI)
results show that only about 23.7% of the participants met the required daily calorie
intake. In comparison, 76.3% of the participants did not meet the normal calorie
needed. Carbohydrates and proteins are major micronutrients that measured the
normal requirement by 93.8% and 54.6%, respectively. Minerals salts and vitamins
showed inadequate intake, especially retinol, beta carotene, folate, and vitamin D.
Fibre intake was insufficient, about 80.4%. The relationship between oxidative stress and inflammatory profiles was investigated in sickle cell patients who took blood
transfusions of two or more units. Results showed biochemical parameters such as
SOD, AST, ALT, Creatinine and Urea, with inflammatory markers such as CRP and
TNF being significantly increased (P = 0.003) in the test group compared to the control
group. Additionally, the results demonstrated a significant positive correlation (P< 0.05
r=) between CRP and IL-6, TNF and Catalase. However, there was a negative
correlation between AST, IL-β, SOD, Creatinine and Urea (P < 0.05 r=).
Haematological parameters, inflammatory markers and the incidence of
alloimmunization in both test and controls were determined. Red cell antibody typing
was determined by saline and anti-human globin (AHG) methods and was interpreted
using the ID panel profile. CRP, TNF, IL-1, IL-6, IL -1β were analysed using enzymelinked
immunosorbent assay (ELISA) technique. Full blood count (FBC) was
processed on an auto-analyser. The test group consisted of patients with SCD
confirmed with haemoglobin electrophoresis who had been transfused with at
least two pints of blood, while those in the control group were not SCD patients but
received the same units of blood. Results showed elevated alloimmunization in SCD
and significantly increased platelet counts compared to the control group. In addition,
the test group displayed evidence of inflammation with significantly increased levels
(P = 0.0001) of C-reactive protein and the pro-inflammatory cytokine TNF. This was
supported by a higher neutrophil count, which can also indicate elevated inflammation.
Furthermore, the pattern of antibodies detected in SCD was anti-Kell, JKa and Fya,
which was different from the control, which displayed anti-M and similarity with Kell
antibodies. There was, however, no significant correlation between inflammatory
markers and alloimmunization. In conclusion, this study shows that undernutrition and inadequate nutrients, if not
corrected, could result in high alloimmunization rates in SCD patients. High levels of
oxidative stress and inflammation also contribute to multidimensional factors liable for
elevated alloimmunization. In the management of SCD, it is imperative that nutritional
monitoring be encouraged alongside medical care to ensure adequate levels of macro
and micronutrients needed for maximum supply for body upkeep.
Additional information
Thesis (DPhil (Biomedical Sciences))--Cape Peninsula University of Technology, 2024
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