Our study confirms that VECs are significant targets of HC in the context of SCD and identifies its earlier unsuspected action on another major component of SCD pathophysiology, that is, the 'inflammation pathway'.
An adult patient affected by b 0 -thalassemia major underwent allogeneic bone marrow transplant (BMT) from a matched related donor. Forty days after transplant, allogeneic engraftment failure and autologous b 0 -thalassemic bone marrow recovery were documented. Red blood cell transfusions were required until 118 days post-transplant. Thereafter, the haemoglobin (Hb) levels stabilized over 11.8 gr/dl throughout the ongoing 34-month follow-up, abolishing the need for transfusion support. The Hb electrophoresis showed 100% Hb Fetal (HbF). This unexplained case suggests full HbF production may occur in an adult patient with b 0 -thalassemia major.Homozygous b-thalassemia is a severe disorder caused by inheritance of two b-thalassemia alleles. The gene mutations produce absent or insufficient synthesis of b-globin chains leading to excess a-globin chain accumulation and precipitation in early erythroid cells [1]. Concurrent genetic factors (hereditary persistence of fetal hemoglobin(HbF), a-gene mutations, and db-thalassemia determinants) are known to modify the globin chain imbalance [1,2].To date, the only cure for thalassemia major is stem cell transplantation [3]. Here, we report an atypical case of sustained and full HbF production after graft failure in an adult b 0 -thalassemic patient.On September 2005, an 18-year-old patient affected by b 0 -thalassemia major was referred to our center for bone marrow transplant (BMT) from an HLA identical sibling. The thalassemia Major diagnosis was evident by 2 years of age when the blood transfusion therapy was started and regularly administered every 2-3 weeks. After splenectomy, performed when the patient was 6 years old, the transfusion requirement was reduced to one red blood cell unit every 2-3 months. Such behavior was maintained during the following years without any transfusion-free period. The iron-chelation therapy was never administered.At the time of presentation to our Institution, the patient presented typical thalassemic facies and hepatomegaly (over 4 cm below the ribs). The complete blood counts showed: low Hb level (9.7 g/dl), low red blood cell count (3.59 3 10 12 /l), a mean corpuscular volume of 82 fl, a mild increase of reticulocyte count (4.07%), increased white cell count (3.901 3 10 12 /l), abundant circulating nucleated red cells (80% of total nucleated cells), and an elevated platelet count (803 3 10 9 /l). The bone marrow exhibited marked hypercellularity. The Hb profile showed predominantly HbF (73.6%), and the genetic analysis detected a double mutation in the b-globin locus: the homozygous mutation IVS-I-1 of the b-globin gene and the homozygous mutation for T variant at position 2158 upstream of the Gg-globin gene. High-performance liquid chromatography (HPLC) analyses detected the lack of b-chain synthesis (b 0%) and 2.47% of the a/non a imbalance.Chronic hepatitis C was documented by a HCV-RNA test. Liver biopsy showed mild fibrosis (1/6 degree) and marked iron overload ([3/4] histological score). The liver iron concentration was marked ...
Human mannose- binding lectin (MBL) plays an important role in innate immunity. MBL deficiency is associated with mutations in the promoter region and in exon 1 of the MBL2 gene. Such deficiency has been correlated with elevated incidence of infections in infancy and in immunocompromised adults. We determined the distribution profile of the MBL2 gene variants in the general population of Benin (West Africa) and in a vulnerable subset of children with sickle cell disease (SCD) (SS homozygotes). Five hundred forty-two healthy individuals (274 newborns, 268 adults) and 128 patients with SCD (35 newborns, 93 children) were screened for the common variant alleles in the MBL2 secretor haplotype region (exon 1 and promoter). The p.G57E variant allele was the most frequent allele compared to p.G54D (27.5% vs. 1.6%, respectively). The p.R52C allele was not found in this population. There was no difference in allele or genotype frequencies between healthy newborns and newborns with SCD. Alleles associated with MBL deficiency were more frequent in adults than in newborns (69.8% vs. 57.3%, respectively; p=0.002). This enrichment was exclusively due to an elevated proportion of heterozygotes for the p.G57E allele (47.0% vs. 35.3%,respectively; p=0.004), supporting a potential selective advantage of this genotype. Our results, compared to those reported in other African countries, support the implication of the MBL2 gene in various major infections in Africa, such as meningitis and tuberculosis in HIV- positive patients.
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