Study of alpha hemoglobin stabilizing protein expression in patients with β thalassemia and sickle cell anemia and its impact on clinical severity

Mahmoud, Hanan M.; Shoeib, Ahmed A.; Ghany, Shereen Mohamed Abd El; Reda, Marwa M.; Ragab, Iman

doi:10.1016/j.bcmd.2015.07.016

Cited by 11 publications

(18 citation statements)

References 22 publications

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“…Different studies suggest that AHSP could be a genetic modifier of b-thal (Weiss et al, 2005). Although there are arguments for both sides, no correlation was found between AHSP expression and the haematological parameters in b-thal patients (Mahmoud et al, 2015) but the AHSP expression level was significantly correlated to MCV, % HbF, a-globin, b-globin and excess a-globin expression in HbE/b-thal patients (Lim et al, 2012).…”

Section: Discussionmentioning

confidence: 92%

“….) Although there are arguments for both sides, no correlation was found between AHSP expression and the haematological parameters in b-thal patients (Mahmoud et al, 2015) but the AHSP expression level was significantly correlated to MCV, % HbF, a-globin, b-globin and excess a-globin expression in HbE/b-thal patients (Lim et al, 2012). If HbF is significantly elevated, XmnI restriction site of the HBG2 gene (Bandyopadhyay et al, 2001;Nguyen et al, 2010) or KLF1 gene mutations (Borg et al, 2010;Liu et al, 2014), polymorphism in BCL11A gene or HBS1L-MYB intergenic region Uda et al, 2008;Wahlberg et al, 2009) should be investigated.…”

Section: Indicationmentioning

confidence: 99%

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Red blood cells free α‐haemoglobin pool: a biomarker to monitor the β‐thalassemia intermedia variability. The ALPHAPOOL study

et al. 2017

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The severity of β-thalassaemia (β-thal) intermedia is mainly correlated to the degree of imbalanced α/non α-globin chain synthesis. The phenotypic diversity of β-thal depends on this imbalance and reflects all possible combinations of α- and β-globin genotypes, levels of fetal haemoglobin (HbF) and co-inheritance of other modulating factors. This study aimed to demonstrate the validity of a new surrogate of α/non α-globin biosynthetic ratio by measuring the soluble α-Hb pool in lysed red blood cells. Our results confirm that the α-Hb pool measurement allows a good discrimination between β-thal intermedia patients, controls and α-thal patients (P < 0·003). Receiver operator characteristic analyses revealed an area under the curve of 0·978 for the α-Hb pool measurement at a threshold of 120 ng free α-Hb/mg of total Hb/ml of haemolysate (ppm) with a sensitivity and specificity of 86% and 100%, respectively, to discriminate between β-thal and not β-thal subjects. Significant correlations were observed between the α-Hb pool and biological parameters of β-thal, the most significant association being observed with red cell hexokinase activity. This study indicates that the α-Hb pool could be a new marker for assistance in diagnostic orientation of β-thal intermedia patients and may be clinically useful for monitoring the evolution of the disequilibrium of globin synthesis in response to treatments.

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Section: Discussionmentioning

confidence: 92%

Section: Indicationmentioning

confidence: 99%

Red blood cells free α‐haemoglobin pool: a biomarker to monitor the β‐thalassemia intermedia variability. The ALPHAPOOL study

et al. 2017

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“…Furthermore, the phenotype was aggravated upon testing with the intermediate Thalassemia genotype, corresponding to the loss of AHSP. 63 By using K562 cells, it was suggested that AHSP can be a candidate genetic modifier in thalassemia patients. 64 It was also reported that an individual in Southern Asia with an AHSP mutation homozygote (Val56>Gly), in the initial year of life shows a clinical syndrome similar to a Thalassemia patient.…”

Section: Element Factors Of Eklf Gata Gdf11 Gdf15 and Ahspmentioning

confidence: 99%

Genetic Background of β Thalassemia Modifier: Recent Update

Rujito

Sasongko

2018

J. Biomed. Transl. Res.

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Thalassemia has become major health problem among developing countries. Genetic background which contain enormous mutations and variations have lead in clinical problem differences.The genetic basis of thalassemia, beta specifically, is mutations of the gene encoding the β chain of the hemoglobin (Beta-Globin, HBB). However, today it is known that abnormalities in this gene do not necessarily determine the clinical appearance of β thalassemia patients.A set of genes has been found that can modify the primary β thalassemia disorder. Secondary modifier contains genes that have been associated with elevated levels of HbF and improvement ratio of α / β globin chain. The genes involved are HBA, HBG, BCL11A, HBS1L-MYB and other cofactor genes regulating erythropoiesis. Tertiary genetic modifier comes from other genes related to the disease severity including iron metabolism, redox activity, and clinical complications. The review aims to provide the latest updates regarding the known β Thalassemia modifier genes and some other genes involved in the changes of the clinical manifestations.

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“…Several studies have used assessments of mRNA levels in circulating reticulocytes based on real‐time reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) to assess AHSP gene expression 4–6 . Lai et al 4 .…”

Section: Introductionmentioning

confidence: 99%

“…They concluded that AHSP might act in a secondary compensatory mechanism in RBCs, counterbalancing the excess α‐globin chain in these patients. In 2015, Mahmoud et al 6 . compared AHSP expression between patients with β‐thal and sickle cell anaemia (SCA), another inherited haemoglobinopathy.…”

Section: Introductionmentioning

confidence: 99%

Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment

et al. 2021

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Summary Alpha haemoglobin‐stabilising protein (AHSP) is a key chaperone synthesised in red blood cell (RBC) precursors. Many studies have reported AHSP as a potential biomarker of various diseases. AHSP gene expression has been studied in detail, but little is known about AHSP protein levels in RBCs. We investigated the AHSP concentration of RBC lysates from control subjects (n = 10) and patients with sickle cell anaemia (SCA) with (n = 10) and without (n = 12) hydroxycarbamide (HC) treatment, to evaluate the clinical relevance of AHSP in SCA. We developed a sandwich enzyme‐linked immunosorbent assay method, with which we were able, for the first time, to determine the mean AHSP concentration in control RBC lysates (0·82 µg/ml). The AHSP concentration (2·23 µg/ml) was significantly higher in untreated patients with the SS genotype than in controls. The AHSP concentration decreased significantly on HC treatment (1·50 µg/ml) but remained significantly higher than that in controls. A strong positive correlation was observed between the AHSP concentration and the α‐haemoglobin pool with the three groups of subjects pooled into a single group. Our present findings indicate that AHSP concentration can be considered a candidate biomarker for monitoring HC responses in patients with SCA and suggest a role for AHSP in various RBC diseases.

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Study of alpha hemoglobin stabilizing protein expression in patients with β thalassemia and sickle cell anemia and its impact on clinical severity

Cited by 11 publications

References 22 publications

Red blood cells free α‐haemoglobin pool: a biomarker to monitor the β‐thalassemia intermedia variability. The ALPHAPOOL study

Red blood cells free α‐haemoglobin pool: a biomarker to monitor the β‐thalassemia intermedia variability. The ALPHAPOOL study

Genetic Background of β Thalassemia Modifier: Recent Update

Alpha haemoglobin‐stabilising protein concentration in the red blood cells of patients with sickle cell anaemia with and without hydroxycarbamide treatment

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