Search results for: reticulocyte

Authors: Aditi Mittal, Nishit Gupta, Tina Dadu, Anil Handoo

Abstract:

Introduction: Hematopoietic stem cell transplantation (HSCT) is a curative treatment done for hematologic malignancies and other clinical conditions. Its main objective is to reconstitute the hematopoietic system of the recipient by administering an infusion of donor hematopoietic stem cells. Transplant engraftment is the first sign of bone marrow recovery. The main objective of this study is to assess immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) as early indicators of post-hematopoietic stem cell transplant engraftment. Methods: Patients of all age groups and both genders undergoing both autologous and allogeneic transplants were included in the study. All the CBC samples were run on Mindray CAL-8000 (BC-6800 plus; Shenzhen, China) analyser and assessed for IPF and IRF. Neutrophil engraftment was defined as the first of three consecutive days with an ANC >0.5 x 109/L and platelet engraftment with a count >20 x 109/L. The cut-off values for IRF were calculated as 13.5% with a CV of 5% and for IPF was 19% with a CV of 12%. Results: The study sample comprised 200 patients, of whom 116 had undergone autologous HSCT, and 84 had undergone allogeneic HSCT. We observed that IRF anticipated the neutrophil recovery by an average of 5 days prior to IPF. Though there was no significant variation in IPF and IRF for the prediction of platelet recovery, IRF was preceded by 1 or 2 days to IPF in 25% of cases. Conclusions: Both IPF and IRF can be used as reliable parameters as predictors for post-transplant engraftment; however, IRF seems to be more reliable than IPF as a simple, inexpensive, and widely available tool for predicting marrow recovery several days before engraftment.

Keywords: transplantation, stem cells, reticulocyte, engraftment

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Authors: Ahmed M. Hjazi, Bader M. Hjazi

Abstract:

Protein 4.1 is a crucial component of complex interactions between the cytoskeleton and other junctional complex proteins. When the gene encoding this protein is altered, resulting in reduced expression, or when the protein is absent, the red cell undergoes a significant structural change. This research aims to achieve a deeper comprehension of the biochemical effects of red cell protein deficiency. A Tandem Mass Spectrometry Analysis (TMT-MS/MS) of patient cells lacking protein 4.1 compared to three healthy controls was achieved by the Proteomics Institute of the University of Bristol. The SDS-PAGE and Western blotting were utilized on the original patient sample and controls to partially confirm TMT MS/MS data analysis of the protein-4.1-deficient cells. Compared to healthy controls, protein levels in samples lacking protein 4.1 had a significantly higher concentration of proteins that probably originated from reticulocytes. This could occur if the patient has an elevated reticulocyte count. The increase in chaperone and reticulocyte-associated proteins was most notable in this study. This may result from elevated quantities of reticulocytes in patients with hereditary elliptocytosis.

Keywords: hereditary elliptocytosis, protein 4.1, red cells, tandem mass spectrometry data.

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Authors: Anthara Vivek, Manisha Shukla, Mahesh Narayan, Prakash Narayan

Abstract:

Sickle cell disease disproportionately affects sub-Saharan Africa and certain tribal populaces in India and has consequently drawn little intertest from Pharma. In sickle cell patients, adhesion of erythrocytes or reticulocytes to one another and the vessel wall results in painful ischemic episodes with few, if any, effective treatments for vaso-occlusive crises. Identification of disease-associated adhesion markers on erythrocytes or reticulocytes might inform the use of more effective therapies against vaso-occlusive crises. Increased expression of one or more of bcam, itga4, cd44, cd47, rap1a, vcam1, or icam4 has been reported in sickle cell subjects. Using the miRNet ontology knowledgebase, peripheral blood interactomes were generated by seeding various combinations of the afore-referenced mRNA. These interactomes yielded an array of miR targets. As examples, targeting hsa-miR-155-5p can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 erythrocyte/reticulocyte adhesion interactome whereas targeting hsa-miRs-103a-3p or 107 can potentially neutralize adhesion in cells overexpressing icam4-cd47-bcam-itga4-cd36. AM3380 (MIRacle™) is an off-the shelf hsa-miR-155-5p agomiR that can potentially neutralize the rap1a-bcam-cd44-itga4-vcam1 signaling axis. Phlebotomy coupled with transcriptomics represents a potentially feasible and effective precision medicine strategy to mitigate vaso-occlusive crises in sickle cell patients.

Keywords: adhesion, interactome, precision, medicine

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Authors: Matthew Cameron, Stephen Yang, Latifa Al Kharusi, Adam Gosselin, Anissa Chirico, Pouya Gholipour Baradari

Abstract:

Background: Iron supplementation has been evaluated in several randomized controlled trials (RCTs) for the potential to increase baseline hemoglobin and decrease the incidence of red blood cell (RBC) transfusion during cardiac surgery. This study's main objective was to evaluate the evidence for iron administration in cardiac surgery patients for its effect on the incidence of perioperative RBC transfusion. Methods: This systematic review protocol was registered with PROSPERO (CRD42020161927) on Dec. 19th, 2019, and was prepared as per the PRISMA guidelines. MEDLINE, EMBASE, CENTRAL, Web of Science databases, and Google Scholar were searched for RCTs evaluating perioperative iron administration in adult patients undergoing cardiac surgery. Each abstract was independently reviewed by two reviewers using predefined eligibility criteria. The primary outcome was perioperative RBC transfusion, with secondary outcomes of the number of RBC units transfused, change in ferritin level, reticulocyte count, hemoglobin, and adverse events, after iron administration. The risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool, and the primary and secondary outcomes were analyzed with a random-effects model. Results: Out of 1556 citations reviewed, five studies (n = 554 patients) met the inclusion criteria. The use of iron demonstrated no difference in transfusion incidence (RR 0.86; 95% CI 0.65 to 1.13). There was a low heterogeneity between studies (I²=0%). The trial sequential analysis suggested an optimal information size of 1132 participants, which the accrued information size did not reach. Conclusion: The current literature does not support the routine use of iron supplementation before cardiac surgery; however, insufficient data is available to draw a definite conclusion. A critical knowledge gap has been identified, and more robust RCTs are required on this topic.

Keywords: cardiac surgery, iron, iron supplementation, perioperative medicine, meta-analysis, systematic review, randomized controlled trial

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Authors: Arsyam Mawardi, Sony Suhandono, Azzania Fibriani, Fifi Fitriyah Masduki

Abstract:

Malaria is an infectious disease caused by Plasmodium sp. This disease has a high prevalence in Indonesia, especially in Jayapura. The vaccine that is currently being developed has not been effective in overcoming malaria. This is due to the high polymorphism in the Plasmodium genome especially in areas that encode Plasmodium surface proteins. Merozoite Surface Protein 1 (MSP1) Plasmodium falciparum is a surface protein that plays a role in the invasion process in human erythrocytes through the interaction of Glycophorin A protein receptors and sialic acid in erythrocytes with Reticulocyte Binding Proteins (RBP) and Duffy Adhesion Protein (DAP) ligands in merozoites. MSP1 can be targeted to be a specific antigen and predicted epitope area which will be used for the development of diagnostic and malaria vaccine therapy. MSP1 consists of 17 blocks, each block is dimorphic, and has been marked as the K1 and MAD20 alleles. Exceptions only in block 2, because it has 3 alleles, among others K1, MAD20 and RO33. These polymorphisms cause allelic variations and implicate the severity of patients infected P. falciparum. In addition, polymorphism of MSP1 in Jayapura isolates has not been reported so it is interesting to be further identified and projected as a specific antigen. Therefore, in this study, we analyzed the allele polymorphism as well as detected the MSP1 epitope antigen candidate on block 2 P. falciparum. Clinical samples of selected malaria patients followed the consecutive sampling method, examining malaria parasites with blood preparations on glass objects observed through a microscope. Plasmodium DNA was isolated from the blood of malarial positive patients. The block 2 MSP1 gene was amplified using PCR method and cloned using the pGEM-T easy vector then transformed to TOP'10 E.coli. Positive colonies selection was performed with blue-white screening. The existence of target DNA was confirmed by PCR colonies and DNA sequencing methods. Furthermore, DNA sequence analysis was done through alignment and formation of a phylogenetic tree using MEGA 6 software and insilico analysis using IEDB software to predict epitope candidate for P. falciparum. A total of 15 patient samples have been isolated from Plasmodium DNA. PCR amplification results show the target gene size about ± 1049 bp. The results of MSP1 nucleotide alignment analysis reveal that block 2 MSP1 genes derived from the sample of malarial patients were distributed in four different allele family groups, K1 (7), MAD20 (1), RO33 (0) and MSP1_Jayapura (10) alleles. The most commonly appears of the detected allele is MSP1_Jayapura single allele. There was no significant association between sex variables, age, the density of parasitemia and alel variation (Mann Whitney, U > 0.05), while symptomatic signs have a significant difference as a trigger of detectable allele variation (U < 0.05). In this research, insilico study shows that there is a new epitope antigen candidate from the MSP1_Jayapura allele and it is predicted to be recognized by B cells with 17 amino acid lengths in the amino acid sequence 187 to 203.

Keywords: epitope candidate, insilico analysis, MSP1 P. falciparum, polymorphism

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