scholarly journals Sickle Cell Trait Modulates the Proteome and Phosphoproteome of Plasmodium falciparum-Infected Erythrocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Margaux Chauvet ◽  
Cerina Chhuon ◽  
Joanna Lipecka ◽  
Sébastien Dechavanne ◽  
Célia Dechavanne ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Erythrocyte Membrane ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Protein Complexes ◽  
Human Populations ◽  
Red Cell Membrane ◽  
High Prevalence ◽  
Erythrocyte Surface ◽  
Human Proteins

The high prevalence of sickle cell disease in some human populations likely results from the protection afforded against severe Plasmodium falciparum malaria and death by heterozygous carriage of HbS. P. falciparum remodels the erythrocyte membrane and skeleton, displaying parasite proteins at the erythrocyte surface that interact with key human proteins in the Ankyrin R and 4.1R complexes. Oxidative stress generated by HbS, as well as by parasite invasion, disrupts the kinase/phosphatase balance, potentially interfering with the molecular interactions between human and parasite proteins. HbS is known to be associated with abnormal membrane display of parasite antigens. Studying the proteome and the phosphoproteome of red cell membrane extracts from P. falciparum infected and non-infected erythrocytes, we show here that HbS heterozygous carriage, combined with infection, modulates the phosphorylation of erythrocyte membrane transporters and skeletal proteins as well as of parasite proteins. Our results highlight modifications of Ser-/Thr- and/or Tyr- phosphorylation in key human proteins, such as ankyrin, β-adducin, β-spectrin and Band 3, and key parasite proteins, such as RESA or MESA. Altered phosphorylation patterns could disturb the interactions within membrane protein complexes, affect nutrient uptake and the infected erythrocyte cytoadherence phenomenon, thus lessening the severity of malaria symptoms.

Cell-mediated immune responses to Plasmodium falciparum purified soluble antigens in sickle-cell trait subjects

1990 ◽  
Vol 25 (1-3) ◽  
pp. 243-249 ◽  
Author(s):  
R.A. Bayoumi ◽  
Y.A. Abu-Zeid ◽  
N.H. Abdulhadi ◽  
B.O. Saeed ◽  
T.G. Theander ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immune Responses ◽  
Sickle Cell ◽  
Sickle Cell Trait

scholarly journals Malaria continues to select for sickle cell trait in Central Africa

2015 ◽  
Vol 112 (22) ◽  
pp. 7051-7054 ◽  
Author(s):  
Eric Elguero ◽  
Lucrèce M. Délicat-Loembet ◽  
Virginie Rougeron ◽  
Céline Arnathau ◽  
Benjamin Roche ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Genetic Disorder ◽  
Central Africa ◽  
The United States ◽  
Malaria Prevalence ◽  
Current Data ◽  
World Health ◽  
Human Populations ◽  
Health Organization

Sickle cell disease (SCD) is a genetic disorder that poses a serious health threat in tropical Africa, which the World Health Organization has declared a public health priority. Its persistence in human populations has been attributed to the resistance it provides to Plasmodium falciparum malaria in its heterozygous state, called sickle cell trait (SCT). Because of migration, SCT is becoming common outside tropical countries: It is now the most important genetic disorder in France, affecting one birth for every 2,400, and one of the most common in the United States. We assess the strength of the association between SCT and malaria, using current data for both SCT and malaria infections. A total of 3,959 blood samples from 195 villages distributed over the entire Republic of Gabon were analyzed. Hemoglobin variants were identified by using HPLCy (HPLC). Infections by three species of Plasmodium were detected by PCR followed by sequencing of a 201-bp fragment of cytochrome b. An increase of 10% in P. falciparum malaria prevalence is associated with an increase by 4.3% of SCT carriers. An increase of 10 y of age is associated with an increase by 5.5% of SCT carriers. Sex is not associated with SCT. These strong associations show that malaria remains a selective factor in current human populations, despite the progress of medicine and the actions undertaken to fight this disease. Our results provide evidence that evolution is still present in humans, although this is sometimes questioned by scientific, political, or religious personalities.

scholarly journals Evidence for both innate and acquired mechanisms of protection from Plasmodium falciparum in children with sickle cell trait

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3808-3814 ◽  
Author(s):  
Lauren Gong ◽  
Catherine Maiteki-Sebuguzi ◽  
Philip J. Rosenthal ◽  
Alan E. Hubbard ◽  
Chris J. Drakeley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Relative Density ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Plasmodium Falciparum Malaria ◽  
Force Of Infection ◽  
Symptomatic Malaria ◽  
Molecular Force ◽  
High Parasite Density ◽  
Within Subjects

AbstractSickle cell trait (HbAS) is known to be protective against Plasmodium falciparum malaria, but it is unclear when during the course of infection this protection occurs and whether protection is innate or acquired. To address these questions, a cohort of 601 children 1-10 years of age were enrolled in Kampala, Uganda, and followed for 18 months for symptomatic malaria and asymptomatic parasitemia. Genotyping was used to detect and follow individual parasite clones longitudinally within subjects. Children with HbAS were protected against the establishment of parasitemia, as assessed by the molecular force of infection at older but not younger ages (at 2 years of age: incidence rate ratio [IRR] = 1.16; 95% confidence interval [95% CI], 0.62-2.19; P = .6; at 9 years of age: IRR = 0.50; 95% CI, 0.28-0.87; P = .01), suggesting an acquired mechanism of protection. Once parasitemic, children with HbAS were less likely to progress to symptomatic malaria, with protection again being the most pronounced at older ages (at 2 years of age: relative risk [RR] = 0.92; 95% CI, 0.77-1.10; P = .3; at 9 years of age: RR = 0.68; 95% CI, 0.51-0.91; P = .008). Conversely, the youngest children were best protected against high parasite density (at 2 years of age: relative density = 0.24; 95% CI, 0.10-0.54; P = .001; at 9 years of age: relative density = 0.59; 95% CI, 0.30-1.19; P = .14), suggesting an innate mechanism of protection against this end point.

scholarly journals Prevalence of sickle cell trait and its association to renal dysfunction among blood donors at university of medical sciences teaching hospital, Ondo, Nigeria

2021 ◽  
Vol 21 (3) ◽  
pp. 1237-1242
Author(s):  
Akinwumi Ayodeji Akinbodewa ◽  
Adeyemi Ogunleye ◽  
Oluseyi Ademola Adejumo
Keyword(s):  
Renal Function ◽  
Sickle Cell ◽  
Blood Donors ◽  
Sickle Cell Trait ◽  
P Value ◽  
Healthy Donors ◽  
Significant Difference ◽  
High Prevalence ◽  
The Mean ◽  
Estimated Glomerular Filtration Rates

Introduction: Prospective blood donors are routinely screened for blood borne infections but medical illnesses and haemo- globin genotype are overlooked despite a high prevalence of haemoglobin AS among Nigerian donors. Objective: To determine the prevalence of haemoglobin AS and its association to renal function, if any. Method: Apparently healthy donors were studied between February and December 2018. Their haemoglobin genotype and, estimated glomerular filtration rates were determined. Results: There were 96 males (94.1%) and 6 (5.9%) females with mean age of 26.7±4.5 years (range 19-44 years) and mean eGFR of 103.97±19.00ml/min/1.73m2. Eighty one (79.4%) and 21 (20.6%) subjects had haemoglobin AA and AS geno- types respectively. The mean eGFR for subjects with haemoglobin AA and AS were 105.2±18.6ml/min/1.73m2 and 99.9 ± 21.2ml/min/1.73m2 respectively (p value = 0.270). Eighty one (79.4%), 20 (19.6%) and 1 (1.0%) subjects had renal function at >90ml/min/1.73m2, 60-89ml/min/1.73m2 and 30-59ml/min/m2 respectively. There was no significant difference in the mean eGFR between subjects with haemoglobin AA and AS (mean difference 5.3, p = 0.265, 95%CI = -4.07 to 14.60). Conclusion: The prevalence of sickle cell trait among Nigerian blood donors is high. There is no significant difference in the renal function status of blood donors with SCT and normal haemoglobin genotype. Keywords: Haemoglobin genotype; sickle cell trait; renal function; blood donor; Nigeria.

Sign in / Sign up

Export Citation Format

Share Document