scholarly journals Red blood cell tension controlsPlasmodium falciparuminvasion and protects against severe malaria in the Dantu blood group

2018 ◽  
Author(s):  
Silvia N. Kariuki ◽  
Alejandro Marin-Menendez ◽  
Viola Introini ◽  
Benjamin J. Ravenhill ◽  
Yen-Chun Lin ◽  
...  
Keyword(s):  
Protective Effect ◽  
Severe Malaria ◽  
Blood Group ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Surface Protein ◽  
Major Effect ◽  
Similar Degree ◽  
Parasite Invasion ◽  
Degree Of Protection

Malaria has had a major effect on the human genome, with many protective polymorphisms such as sickle cell trait having been selected to high frequencies in malaria endemic regions1, 2. Recently, we showed that a novel blood group variant, Dantu, provides 74% protection against all forms of severe malaria in homozygous individuals3-5. This is a similar degree of protection to sickle cell trait and considerably greater than the most advanced malaria vaccine, but until now the mechanism of protection has been unknown. In the current study, we demonstrate a significant impact of Dantu on the ability ofPlasmodium falciparummerozoites to invade RBCs. The Dantu variant was associated with extensive changes to the RBC surface protein repertoire, but unexpectedly the malaria protective effect did not correlate with specific RBC-parasite receptor-ligand interactions. By following invasion using video microscopy, we found a strong link between RBC tension and parasite invasion and, even in non-Dantu RBCs, identified a tension threshold above which RBC invasion did not occur. Dantu RBCs had higher average tension, meaning that a higher proportion of Dantu RBCs could not be invaded. These findings not only provide an explanation for the protective effect of Dantu against severe malaria, but also provide fresh insights into the essential process ofP. falciparumparasite invasion, and how invasion efficiency varies across the heterogenous populations of RBCs that are present both within and between individuals.

Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria

Acta Tropica ◽  
2012 ◽  
Vol 123 (2) ◽  
pp. 72-77 ◽  
Author(s):  
O.K. Amodu ◽  
S.A. Olaniyan ◽  
A.A. Adeyemo ◽  
M. Troye-Blomberg ◽  
P.E. Olumese ◽  
...  
Keyword(s):  
Blood Group ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Clinical Severity ◽  
Abo Blood Group ◽  
Southwest Nigeria

scholarly journals Sickle-trait hemoglobin reduces adhesion to both CD36 and EPCR by Plasmodium falciparum-infected erythrocytes

2021 ◽  
Vol 17 (6) ◽  
pp. e1009659
Author(s):  
Jens E. V. Petersen ◽  
Joseph W. Saelens ◽  
Elizabeth Freedman ◽  
Louise Turner ◽  
Thomas Lavstsen ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Severe Malaria ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Surface Expression ◽  
Endothelial Protein C Receptor ◽  
And Function ◽  
Adhesion Assays

Sickle-trait hemoglobin protects against severe Plasmodium falciparum malaria. Severe malaria is governed in part by the expression of the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) that are encoded by var genes, specifically those variants that bind Endothelial Protein C Receptor (EPCR). In this study, we investigate the effect of sickle-trait on parasite var gene expression and function in vitro and in field-collected parasites. We mapped var gene reads generated from RNA sequencing in parasite cultures in normal and sickle-cell trait blood throughout the asexual lifecycle. We investigated sickle-trait effect on PfEMP1 interactions with host receptors CD36 and EPCR using static adhesion assays and flow cytometry. Var expression in vivo was compared by assembling var domains sequenced from total RNA in parasites infecting Malian children with HbAA and HbAS. Sickle-trait did not alter the abundance or type of var gene transcripts in vitro, nor the abundance of overall transcripts or of var functional domains in vivo. In adhesion assays using recombinant host receptors, sickle-trait reduced adhesion by 73–86% to CD36 and 83% to EPCR. Similarly, sickle-trait reduced the surface expression of EPCR-binding PfEMP1. In conclusion, Sickle-cell trait does not directly affect var gene transcription but does reduce the surface expression and function of PfEMP1. This provides a direct mechanism for protection against severe malaria conferred by sickle-trait hemoglobin. Trial Registration: ClinicalTrials.gov Identifier: NCT02645604.

ANTI-hrs associated with the RHD-RHCE HAPLOTYPE DAR-ceAR in a patient with Sickle Cell Trait

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4066-4066
Author(s):  
Sidneia Sanches Costa ◽  
A. K Chiba ◽  
F. O Martin ◽  
Dante M Langhi ◽  
C. S Chiattone ◽  
...  
Keyword(s):  
Blood Group ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Black Population ◽  
Test Tube ◽  
Blood Group System ◽  
Title 1 ◽  
Group A ◽  
Rare Phenotype ◽  
Clinically Significant

Abstract Introduction: The RH blood group system is the most polymorphic and immunogenic among blood groups and some rare Rh phenotypes are found exclusively in the black population. The RH 18 phenotype (Hr-negative) that is one of these phenotypes is characterized by a high incidence antigen. The production of anti-RH 18 imposes to use equivalent rare antigen-negative red blood cells (RBCs), or deleted-Rh RBCs (Rhnull or D- -) for transfusion. Case Report: A 24-year-old female patient with two previous abortions and one ectopic pregnancy and miscarriage had to be transfused with a RBC unit. She was typed as blood group A, Dccee phenotype with weak D, positive RBC antibody screening, auto-control negative and TAD negative. The antibody was anti-e (title 1/64) determined by testing serum against a commercial RBC panel (Fresenius-Kabi) by IgG indirect antiglobulin test tube (PEG-IAT), and nontreated (LissCoombs) and papain-treated RBCs on a gel matrix (DiaMed, Latino America). After adsorption of serum on Rhe-negative RBC (DccEE), the retrieving antibody was an anti-e-like antibody reacting with all normal Rhe-positive RBCs. Molecular and serologic Rh typing was also performed on blood samples obtained from five relatives of the patient and her husband. Results: Patient and relatives cDNA sequence of gene RHD and RHCE transcripts were analyzed for RHCE exons 4 to 5 and exon 6; for RHD exons 4 to 5, 6 and 7. Sequencing of cDNA from the patient, her father and her sister showed in RHD the presence of the DAR allele point mutation 602 C>G in exon 4; 667 T>G and 744 C>T in exon 5; 957 G>A and 1025 T>C in exon 7; while on gene RHCE we found the ceAR allele carrying 712 A>G, 733 C>G e 787 A>G in exon 5. Hemoglobin tests revealed that the patient, her father and sister had a sickle cell trait (patient HbA1=55%; HbA2=2,8%; HbS=41%; HbF=1,2%; father HbA1=58,5%; HbA2=1,4%; HbS=37,7%; HbF=2,4%; sister HbA1=57,4%; HbA2=2,5%; HbS=38,6%; HbF=1,5%). Discussion: The family study showed that the haplotype DAR-ceAR was inherited from her father. Individuals carrying the ceAR allele may produce anti-hrs antibody that is defined as a Rhe-like which does not react with rare Rhe positive variant RBCs. The antibody may be clinically significant and represents a great risk for those patients who are not transfused with a similar rare phenotype variant. Serologically, DAR has shown weaker reactions with anti-D, it is characterized by complete loss of at least 9 of 37 RhD epitopes, and may produce anti-D. Both mutated alleles show a replacement of RHD exons by RHCE counterparts.

scholarly journals INFLUENCE OF SICKLE CELL GENE ON THE ALLELIC DIVERSITY AT THE MSP-1 LOCUS OF PLASMODIUM FALCIPARUM IN ADULT PATIENTS WITH SEVERE MALARIA

2015 ◽  
Vol 7 ◽  
pp. e2015050 ◽  
Author(s):  
Dilip Kumar Patel ◽  
Ranjeet Singh Mashon ◽  
Prasanta Purohit ◽  
Siris Patel ◽  
Satyabrata Meher ◽  
...  
Keyword(s):  
Severe Malaria ◽  
Falciparum Malaria ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Allelic Diversity ◽  
Adult Patients ◽  
Medical Sciences ◽  
Hemoglobin Variants ◽  
Biology Laboratory ◽  
Severe Falciparum Malaria

Although several studies have supported that sickle cell trait (HbAS) protects against falciparum malaria, the exact mechanism by which sickle gene confers protection is unclear. Further, there is no information on the influence of sickle gene on parasitic diversity of P. falciparum population in severe symptomatic malaria.  This study was undertaken to assess the effect of the sickle gene on the parasite densities and diversities in hospitalized adult patients with severe falciparum malaria. The study was carried out in 166 adult hospitalized subjects with severe falciparum malaria at Sickle Cell Clinic and Molecular Biology Laboratory, Veer Surendra Sai Institute of Medical Sciences and Research, Burla, Odisha, India . They were divided into three groups on the basis of hemoglobin variants HbAA (n=104), HbAS (n=30) and HbSS (n=32). The msp-1 loci was genotyped using a PCR based methodology. The parasite densities were significantly high in HbAA compared to HbAS and HbSS. The multiplicity of infection (MOI) and multiclonicity for msp-1 were significantly low in HbSS and HbAS compared to HbAA. The prevalence of K1 (p<0 .0001) and MAD20 (p=0.0003) alleles were significantly high in HbAA. The RO33 allele was detected at a higher frequency in HbSS and HbAS, compared to K1 and MAD20. Sickle gene was found to reduce both the parasite densities and diversity of P. falciparum in adults with severe malaria.

Sickle cell trait and the eye

1977 ◽  
Vol 137 (3) ◽  
pp. 281a-281
Author(s):  
P. E. Mickelson
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait

Microsurgery in the Sickle Cell Trait Population: Is It Actually Safe?

2020 ◽  
pp. 1-2
Author(s):  
Michael Alperovich ◽  
Eric Park ◽  
Michael Alperovich ◽  
Omar Allam ◽  
Paul Abraham
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Free Flap ◽  
Near Infrared ◽  
Sickle Cell Trait ◽  
Cell Disease ◽  
Flap Transfer ◽  
Free Flap Transfer ◽  
Patient Reported ◽  
Deep Inferior Epigastric Perforator

Although sickle cell disease has long been viewed as a contraindication to free flap transfer, little data exist evaluating complications of microsurgical procedures in the sickle cell trait patient. Reported is the case of a 55-year-old woman with sickle cell trait who underwent a deep inferior epigastric perforator (DIEP) microvascular free flap following mastectomy. The flap developed signs of venous congestion on postoperative day two but was found to have patent arterial and venous anastomoses upon exploration in the operating room. On near-infrared indocyanine green angiography, poor vascular flow was noted despite patent anastomoses and strong cutaneous arterial Doppler signals. Intrinsic microvascular compromise or sickling remains a risk in the sickle cell trait population as it does for the sickle cell disease population. Just like in sickle cell disease patients, special care should be taken to optimize anticoagulation and minimize ischemia-induced sickling for patients with sickle cell trait undergoing microsurgery.

scholarly journals COVID-19 as a trigger for splenic infarction in a patient with sickle cell trait: a case report

2021 ◽  
pp. 100047
Author(s):  
Álvaro Alejandre-de-Oña ◽  
Jaime Alonso-Muñoz ◽  
Pablo Demelo-Rodríguez ◽  
Jorge del-Toro-Cervera ◽  
Francisco Galeano-Valle
Keyword(s):  
Case Report ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Splenic Infarction

scholarly journals Metabolism of Heterogenic Hemoglobins

Blood ◽  
1963 ◽  
Vol 22 (3) ◽  
pp. 334-341 ◽  
Author(s):  
RICHARD D. LEVERE ◽  
HERBERT C. LICHTMAN ◽  
Joan Levine
Keyword(s):  
Pulmonary Tuberculosis ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Hemoglobin S ◽  
Active Pulmonary Tuberculosis ◽  
Hemoglobin A ◽  
Abnormal Hemoglobin

Abstract The relative rates of incorporation of Fe59 into heterogenic hemoglobins was studied in four patients with sickle cell trait. Three of the patients were free of superimposed disease, while one had active pulmonary tuberculosis. In all subjects there was a significantly greater incorporation of radioiron, per milligram of hemoglobin, into hemoglobin S than into hemoglobin A. The data indicate that in sickle cell trait the rates of synthesis of the heterogenic hemoglobins are not proportional to their circulating concentrations. Two interpretations appear possible. Since the size of the intra-marrow pool of hemoglobin S was not known, it is possible that there exists a smaller preformed pool of the abnormal hemoglobin, with the isotope making its appearance first in hemoglobin S. However, it is also possible that hemoglobin S is synthesized at a rate which is greater than that reflected by its circulating concentration. This implies that the relative concentrations of hemoglobin S and hemoglobin A vary from erythrocyte to erythrocyte, and that those cells with the greatest proportion of hemoglobin S are selectively destroyed.

scholarly journals Allelic diversity of merozoite surface protein genes (msp1 and msp2) and clinical manifestations of Plasmodium falciparum malaria cases in Aceh, Indonesia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Kurnia Fitri Jamil ◽  
Nandha Rizki Pratama ◽  
Sylvia Sance Marantina ◽  
Harapan Harapan ◽  
Muhammad Riza Kurniawan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Liver Function ◽  
Severe Malaria ◽  
Clinical Manifestation ◽  
Allelic Diversity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Malaria Control Programme ◽  
Co Morbidity ◽  
Aceh Province

Abstract Background The malaria control programme in Indonesia has successfully brought down malaria incidence in many parts in Indonesia, including Aceh Province. Clinical manifestation of reported malaria cases in Aceh varied widely from asymptomatic, mild uncomplicated to severe and fatal complications. The present study aims to explore the allelic diversity of merozoite surface protein 1 gene (msp1) and msp2 among the Plasmodium falciparum isolates in Aceh Province and to determine their potential correlation with the severity of malaria clinical manifestation. Methods Screening of over 500 malaria cases admitted to the hospitals in 11 districts hospital within Aceh Province during 2013–2015, identified 90 cases of P. falciparum mono-infection without any co-morbidity. The subjects were clinically phenotyped and parasite DNA was extracted and polymerase chain reaction (PCR) amplified for the msp1 and msp2 allelic subfamilies. Results Analysis of clinical manifestation revealed that fever-chill is the most frequent symptom. Based on WHO criteria showed 19 cases were classified as severe and 71 as mild malaria. Analysis of msp1 gene revealed the presence of K1 allele subfamily in 34 subjects, MAD20 in 42 subjects, RO33 in 1 subject, and mixed allelic of K1 + MAD20 in 5 subjects, K1 + RO33 in 4 subjects, and MAD20 + RO33 in 4 subjects. Analysis of msp2 gene revealed 34 subjects carried the FC27 allelic subfamily, 37 subjects carried the 3D7 and 19 subjects carried the mixed FC27 + 3D7. Analysis of multiplicity of infection revealed that msp1 alleles is slightly higher than msp2 with the mean of MOI were 2.69 and 2.27, respectively. Statistical analysis to determine the association between each clinical manifestation and msp1 and msp2 alleles revealed that liver function abnormal value was associated with the msp2 mixed alleles (odds ratio (OR):0.13; 95%CI: 0.03–0.53). Mixed msp1 of K1 + RO33 was associated with severe malaria (OR: 28.50; 95%CI: 1.59–1532.30). Conclusion This study found a strong association between severe malaria in Aceh with subjects carrying the msp1 mixed alleles of K1 and RO33. The liver function abnormal value associated with the msp2 mixed allelic subfamilies. Further study in different geographic areas is recommended.

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