ReviewAbnormality of erythrocyte membrane n-3 long chain polyunsaturated fatty acids in sickle cell haemoglobin C (HbSC) disease is not as remarkable as in sickle cell anaemia (HbSS)
Introduction
Although less common on a global scale than homozygous (HbSS) sickle cell disease (SCD), the compound heterozygous sickle cell-haemoglobin C (HbSC) is one of the most prevalent sickling disorders. It results from the inheritance of one gene for sickled haemoglobin (HbS) from one parent, and the gene for HbC from the other. HbS has valine in the 6th amino acid position of the beta globin chain, instead of glutamic acid as found in normal adult haemoglobin (HbA). HbC has lysine in the same position 6 occupied by valine in HbS [1]. In people with genotype HbSC, approximately 50% of the total haemoglobin in circulation is HbS [2], [3]. The rest is predominantly HbC, with small proportions of fetal haemoglobin (HbF) and HbA2. Whereas homozygous inheritance of either HbS or HbC causes erythrocyte abnormalities and clinical illness, the condition of HbCC individuals is very mild in comparison to HbSS disease. In the compound heterozygous (HbSC) state, the two variant haemoglobins interact to produce abnormalities of red blood cells, and disease generally less severe than HbSS [4], [5].
HbSC and HbSS diseases and their clinical features have considerable similarity. However, HbSC disease is characterised by a lower overall mortality [4], [5] and a prevalence of cholelithiasis, leg ulcers, hepatomegaly, and cardiomegaly [6], [7]. The reasons for these differences are not fully understood. Nevertheless, differences in erythrocytes in half-life, degree of dehydration, adhesiveness, aggregability and percent of serine phosphoglycerides (SPG) in the outer leaflet of lipid membrane have been implicated. These factors are central to the pathogenesis of blood vessel occlusion and destruction of erythrocytes, which are fundamental pathological processes in the sickle cell disorders [3], [8], [9], [10], [11]. Abnormalities of phospholipid molecular species [12], and fatty acid composition of erythrocytes [13] and platelets and mononuclear cells [14] have been reported in HbSS patients. There are no compressive published reports on blood fatty acid status of HbSC. Since n-3 long chain polyunsaturated fatty acids (LCPUFA) have beneficial effects on trans-membrane ion flux, cell hydration, rheology, and deformability [15], [16], [17], [18], we have investigated if HbSS and HbSC patients have contrasting membrane fatty acid composition consistent with the widely recognised difference in clinical severity between the two disease entities.
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Subjects
Adult African/Caribbean HbSS (age 19–65 years, ) and HbSC (age 26–45 years, ) patients, and racially matched healthy controls (age 20–52, ) were enrolled from St. Thomas’ Hospital, Medical School, London, UK. All the patients were in steady state—defined as the absence of sickle cell crisis or acute illness from 1 month before, and up to 2 weeks after blood sampling for the study. HbSS or HbSC individuals with HbF up to 10%, any other medical diagnosis in addition to SCD, pregnancy
Haemoglobin levels and leukocyte counts
The HbSC group had higher haemoglobin (11.5 vs. 9.0 g/dl, ) and lower leukocyte count (7.0×109/l vs. 10.3×109/l, ) compared with the HbSS patients.
Erythrocyte fatty acids
Fatty acid composition of erythrocyte choline, ethanolamine and serine PS of the HbSC and HbSS patients and healthy HbAA controls is given in Table 1.
Choline phosphoglycerides (CPG). The HbSC patients had higher linoleic (LA, ) docosahexaenoic (DHA, ) and lower arachidonic (AA, ), docosatetraenoic (DTA, 22:4n-6, ),
Discussion
The results show that both HbSS and HbSC patients have abnormal plasma and erythrocyte membrane fatty acid composition. The abnormality is characterised by an increase in the n-6 long-chain polyunsaturated fatty acids (LCPFA), particularly AA, and a concomitant decrease in the n-3 LCPFA, specifically EPA and docosahexaenoic (DHA). As it is evident from the tables, the study also reveals that the abnormality is less pronounced in the HbSC than in the HbSS patients.
The differences in erythrocyte
Acknowledgments
The Mother and Child Foundation, Sir Halley Stewart Trust, and Thomas H. Smouse Memorial Fellowship Award from the American Oil Chemists’ Society supported this study.
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