Beta-thalassaemia Subjects Research Articles

COVID-19: beta-thalassemia subjects immunised?

The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent PRE-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta-chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research.

Safety Study for Beta Thalassemia Subjects on PTG-300

Safety Study for Beta Thalassemia Subjects on PTG-300

Relative proteome quantification of alpha, beta, gamma and delta globin chains in early eluting peaks of Bio-Rad variant II® CE-HPLC of hemoglobin from healthy and beta-thalassemia subjects in Malaysia

This is the first report of QQQ-mass spectrometric identification and quantification of the Hb subunits, alpha, beta, delta and gamma globin peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the Bio-Rad cation-exchange chromatography of haemoglobin. The objectives were to assess the relationship of the quantity of the free alpha, beta, delta and gamma globin chains with the phenotypic diversity of beta-thalassaemias (β-thal). The results demonstrate that the pools of free globin chains in red blood cells were correlating with the severity of the disease in patients with different phenotypes of β-thal. The mechanism and the regulation of synthesis of free globin chains pool in a normal individual and in patients with different β-thal phenotypes could arise from several mechanisms which will require further investigation. The role of the free globin pool in patients with β-thal for development of novel therapeutic approaches based on these potential targets requires further investigation. Pertinent biomarkers improves the diagnosis of the β-thal, especially in low-income countries where they are most common and allows more effective therapeutic intervention leading to more successful therapeutic outcome.

XmnI polymorphism frequency in heterozygote beta thalassemia subjects and its relation to Fetal hemoglobin levels

(7) Additionally, the IVS-I110 (25.64%) and IVS-I-6 (5.12%) were found as were other unidentified mutations (8.9%). There was no statistical difference between the presence of the XmnI polymorphism and beta thalassemia mutations (p = 0.99). In conclusion, the XmnI polymorphism influences Hb F concentrations in patients with the beta-thalassemia trait. The presence of the polymorphic site showed no difference between heterozygous beta-thalassemia carriers and control subjects. The average levels of Hb F in individuals with heterozygous beta-thalassemia and with the XmnI polymorphism were higher than normal, showing the influence of this site on the gene expression of γ-globin.

Discriminant analysis of iron deficiency anaemia and heterozygous thalassaemia traits: a 3-dimensional selection of red cell indices

The two main causes of microcytic and hypochromic anaemia are iron deficiency and thalassaemia traits. Discriminant analysis based on a simple combination of classical red cell indices have been used to differentiate between iron deficiency anaemia and thalassaemia with varying degree of accuracy. Two new indices are now available from modern cell counters: red cell distribution width (RDW) and haemoglobin concentration distribution (HDW). Our discriminant analysis suggests that RBC, MCHC and RDW contribute significantly to the differentiation between iron deficiency anaemia and thalassaemia in both healthy donors and hospital-patient groups. In the discriminating process, previous workers have overlooked the heterogeneity of anaemia between anaemic groups as well as biological differences in MCV and MCH among the alpha and beta thalassaemia subjects. This study took into account of these biases and proved, for the first time, that differentiation between iron deficiency and thalassaemia by discriminant analysis was clinically reliable and not significantly biased by the severity of anaemia. The diagnostic accuracy of discriminant analysis was confirmed retrospectively by the reallocation algorithm using the jack-knife principle and prospectively by testing the discriminant functions on independent new samples. Selection of the red cell indices contributing to the discrimination of microcytic hypochromic anaemia was based on biological and statistical considerations. The clear separation of red cell index data of iron deficiency anaemia and thalassaemia traits was shown 3-dimensionally by surface plots.

Heterocellular hereditary persistence of fetal haemoglobin affects the haematological parameters of beta-thalassaemia trait.

To assess and define the effects of heterocellular hereditary persistence of fetal haemoglobin (HPFH) on the haematological phenotype of heterozygous beta-thalassaemia, we have studied a large kindred that included a total of 204 subjects with 60 beta-thalassaemia carriers, of whom 35 were also heterozygous, and five homozygous, for heterocellular HPFH. The study was possible because of the homogeneity of the beta-thalassaemia mutation and the ability to genotype the heterocellular HPFH allele. Heterocellular HPFH had a significant effect on the mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and haemoglobin (Hb) A2 values in the beta-thalassaemia carriers and accounted for 29%, 30% and 24% of their respective variances. beta-thalassaemia subjects with heterocellular HPFH had higher MCV and MCH values, concomitant with lower levels of Hb A2, and a reduced ineffective erythropoiesis. We conclude that co-inheritance of heterocellular HPFH leads to a primary increase in gamma-chain synthesis in beta-thalassaemia trait and can be another confounding factor in the use of red cell indices and Hb A2 levels in population screening for beta-thalassaemia.

Organization of the zeta-alpha genes in Chinese.

Analysis of alpha and zeta genes in 101 healthy normals and hospitalized patients with non-haematological diseases revealed a 3% incidence of alpha thalassaemia in the local Chinese population of Hong Kong. Triple alpha genes were found in only one person while triple zeta genes were more prevalent, occurring in 13 subjects. Studies of 28 unselected patients with Hb H disease indicated a predominance of the rightward alpha gene deletion. The extent of alpha gene deletion in homozygous alpha thalassaemia 1 was at least 18.1 kb, beginning from the BamH I site 3' to the zeta 1 gene and includes the psi alpha, alpha 2 and alpha 1 genes. Nineteen of the 20 chromosomes bearing the alpha thalassaemia 1 deletion had identical zeta-intergenic hypervariable region suggesting a common origin of this mutation. The co-inheritance of alpha thalassaemia in beta thalassaemia subjects was 8%, but did not ameliorate the clinical features of those with homozygous beta thalassaemia.

Folic acid deficiency in beta-thalassaemia heterozygotes.

Plasma and red cell folate mean contents have been found to be significantly lower in 41 symptom-free beta-thalassaemia heterozygotes than in 21 controls. Such decreases must be considered as effects of an increased folate utilization caused by the enhanced total, both effective and ineffective, erythropoiesis. Since no close correlation has been found between packed cell volume and plasma or red blood cell folate levels, it seems that in 'healthy' beta-thalassaemia subjects, the degree of anaemia is not influenced by folate body reserves. However, the frequent finding of reduced red cell folate contents suggests that further folate imbalance might lead to clinically significant degrees of folate deficiency.

Quantitation of human gamma globin genes and gamma globin mRNA with purified gamma globin complementary DNA.

Complementary DNA (cDNA) specific for gamma-globin nucleotide sequences has been prepared by hybridizing total cDNA made from cord blood messenger RNA (mRNA) as template to an excess of normal adult human globin mRNA and recovering the single-stranded cDNA from hydroxylapatite. The specificity of the gamma cDNA for gamma mRNA sequences is strongly supported by the hybridization of this cDNA at low Cot values (Co, concentration of RNA and t, time in seconds) to RNA samples containing large amounts of functional gamma globin mRNA and the lack of hybridization to RNA samples containing little, if any, gamma-globin mRNA. The absence of cross-hybridization of gamma cDNA with alpha, beta, and delta mRNAs is demonstrated by the complete hybridization of the gamma cDNA to mRNA samples completely lacking either alpha or beta and delta mRNA. An estimate of the number of gamma-globin genes in human cellular DNA was obtained by hybridization of purified gamma cDNA to DNA from spleen and white blood cells of normal and beta-thalassemia subjects and measurement of the percent of gamma cDNA hybridized at saturation. The results indicate that there are between one and two gamma-globin genes per total haploid gene DNA equivalent obtained from both normal and beta-thalassemia subjects. These values are consistent with genetic evidence for the presence of multiple gamma gene loci in human cells. The finding that the number of gamma-globin genes in beta-thalassemia DNA is similar to that in nonthalassemia DNA indicates that a deletion of gamma-globin genes cannot account for either the inadequate gamma-globin synthesis or indirectly for the decreased or absent beta-globin synthesis in beta-thalassemia cells.

Relative numbers of human globin genes assayed with purified alpha and beta complementary human DNA.

Purified alpha and beta globin complementary DNAs (cDNAs) have been separated from total radioactively labeled human globin cDNA using mRNA purified from liver of a hydrops fetalis (alpha thalassemia). The beta cDNA hybridizes to the hydrops fetalis mRNA while the alpha cDNA remains single-stranded. the purified alpha and beta cDNAs were assayed for their purity by their hybridization to mRNA prepared from reticulocytes of nonthalassemia, alpha thalassemia, and beta thalassemia subjects. The results indicate that the separated cDNAs are selective in hybridization to alpha or beta globin mRNAs, respectively. The previously reported deficiency of globin mRNA in thalassemia cells has been confirmed with these purified cDNAs. The purified alpha and beta cDNAs were hybridized to cellular DNA to non-thalassemia, beta+ thalassemia, and hydrops fetalis (alpha thalassemia) DNA. The alpha cDNA hybridized to hydrops fetalis liver DNA to a much lower extent that beta cDNA, confirming the previously reported deletion of alpha globin genes in hydrops fetalis. By contrast, both the alpha and beta DNA probes hybridized to the same extent to spleen DNA from non-thalassemia and from beta+ thalassemia patients. Between two and five globin genes in non-thalassemia and beta+ thalassemia DNA hybridize to beta cDNA and one to five to alpha cDNA. These studies indicate that in beta+ thalassemia, there is no detectable deletion in beta globin genes. The genetic defect in beta+ thalassemia appears to be due to either repression of transcription of beta globin genes or abnormal processing of beta globin mRNA.