scholarly journals IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cyril Badaut ◽  
Pimnitah Visitdesotrakul ◽  
Aurélie Chabry ◽  
Pascal Bigey ◽  
Bernard Tornyigah ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Hospital Admission ◽  
Cerebral Malaria ◽  
Erythrocyte Membrane ◽  
Uncomplicated Malaria ◽  
Clinical Status ◽  
Severe Anemia ◽  
Specific Interactions ◽  
Time Of Admission

AbstractThe Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBLβ3 domain binding to EPCR and ICAM-1 receptors, respectively. This type of PfEMP1 proteins with dual binding specificity mediate specific interactions with brain micro-vessels endothelium leading to the development of cerebral malaria (CM). Using plasma collected from children at time of hospital admission and after 30 days, we study an acquisition of IgG response to PF3D7_1150400/PF11_0521 DC13 and DBLβ3_D4 recombinant constructs, and five peptides located within these constructs, specifically in DBLα1.7_D2 and DBLβ3_D4 domains. We found significant IgG responses against the entire DC13, PF11_0521_DBLβ3_D4 domain, and peptides. The responses varied against different peptides and depended on the clinical status of children. The response was stronger at day 30, and mostly did not differ between CM and uncomplicated malaria (UM) groups. Specifically, the DBLβ3 B3-34 peptide that contains essential residues involved in the interaction between PF11_0521 DBLβ3_D4 domain and ICAM-1 receptor demonstrated significant increase in reactivity to IgG1 and IgG3 antibodies at convalescence. Further, IgG reactivity in CM group at time of admission against functionally active (ICAM-1-binding) PF11_0521 DBLβ3_D4 domain was associated with protection against severe anemia. These results support development of vaccine based on the PF3D7_1150400/PF11_0521 structures to prevent CM.

Identifying targets of protective antibodies against severe malaria in Papua, Indonesia using locally expressed domains of Plasmodium falciparum Erythrocyte Membrane Protein 1.

2021 ◽  
Author(s):  
Janavi S Rambhatla ◽  
Gerry Q Tonkin-Hill ◽  
Eizo Takashima ◽  
Takafumi Tsuboi ◽  
Rintis Noviyanti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Severe Malaria ◽  
Erythrocyte Membrane ◽  
Uncomplicated Malaria ◽  
Igg Antibodies ◽  
Erythrocyte Membrane Protein ◽  
African Children ◽  
Genes Encoding ◽  
Malaria Severity

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a diverse family of multi-domain proteins expressed on the surface of malaria-infected erythrocytes, is an important target of protective immunity against malaria. Our group recently studied transcription of the var genes encoding PfEMP1 in individuals from Papua, Indonesia with severe or uncomplicated malaria. We cloned and expressed domains from 32 PfEMP1s including 22 that were upregulated in severe malaria and 10 that were upregulated in uncomplicated malaria, using a wheat germ cell-free expression system. We used Luminex technology to measure IgG antibodies to these 32 domains and control proteins in 63 individuals (11 children). At presentation to hospital, levels of antibodies to PfEMP1 domains were either higher in uncomplicated malaria or were not significantly different between groups. Using principal components analysis, antibodies to three of 32 domains were highly discriminatory between groups. These included two domains upregulated in severe malaria, a DBLβ13 domain and a CIDRα1.6 domain (which has been previously implicated in severe malaria pathogenesis), and a DBLδ domain that was upregulated in uncomplicated malaria. Antibody to control non-PfEMP1 antigens did not differ with disease severity. Antibodies to PfEMP1 domains differ with malaria severity. Lack of antibodies to locally expressed PfEMP1 types, including both domains previously associated with severe malaria and newly identified targets, may in part explain malaria severity in Papuan adults. Importance Severe Plasmodium falciparum malaria kills many African children, and lack of antibody immunity predisposes to severe disease. A critical antibody target is the P. falciparum erythrocyte membrane 1 (PfEMP1) family of multidomain proteins, which are expressed on the infected erythrocyte surface and mediate parasite sequestration in deep organs. We previously identified var genes encoding PfEMP1 that were differentially expressed between severe and uncomplicated malaria in Papua, Indonesia. Here, we have expressed domains from 32 of these PfEMP1s and measured IgG antibody responses to them in Papuan adults and children. Using Principal Component Analysis, IgG antibodies to three domains distinguished between severe and uncomplicated malaria and were higher in uncomplicated malaria. Domains included CIDRα1.6, implicated in severe malaria; a DBLβ13 domain; and a DBLδ domain of unknown function. Immunity to locally relevant PfEMP1 domains may protect from severe malaria. Targets of immunity show important overlap between Asian adults and African children.

scholarly journals Expression of the Domain Cassette 8 Plasmodium falciparum Erythrocyte Membrane Protein 1 Is Associated with Cerebral Malaria in Benin

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e68368 ◽  
Author(s):  
Gwladys I. Bertin ◽  
Thomas Lavstsen ◽  
François Guillonneau ◽  
Justin Doritchamou ◽  
Christian W. Wang ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Cerebral Malaria ◽  
Erythrocyte Membrane ◽  
Erythrocyte Membrane Protein ◽  
Falciparum Erythrocyte Membrane Protein

scholarly journals Deteksi Protein 270 kDa Plasmodium falciparum Isolat Malang pada Membran Eritrosit Penderita Malaria dengan Komplikasi

2018 ◽  
Vol 6 (2) ◽  
pp. 331
Author(s):  
Dewi Indiastari ◽  
Sri Winarsih ◽  
Loeki Enggar Fitri
Keyword(s):  
Molecular Weight ◽  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Polyclonal Antibody ◽  
Uncomplicated Malaria ◽  
Infected Erythrocyte ◽  
Malaria Patient ◽  
Complicated Malaria ◽  
Falciparum Erythrocyte Membrane Protein

Erythrocyte which is infected by Plasmodium falciparum will have various changes on its architecture, affinity, and biomolecular. Beside that, the infected erythrocyte also forms a knob at its surface. This knob are contained with various parasite proteins, one of them is Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1). Our previous study had been identified a protein with molecular weight 270 kDa at P. falciparum infected erythrocyte from Malang isolate that was playing a role in cytoadherence process. The aim of this study was to detect the possibility of 270 kDa protein expression at complicated malaria falciparum patient erythrocyte membrane. The method that used was immunocytochemistry with polyclonal antibody to 270 kDa protein. The results showed that two (2) erythrocyte samples from healthy people as control had negative reaction, and so did with five (5) erythrocyte samples of uncomplicated malaria patient, but there was positive reaction that shown at two (2) samples of complicated malaria patient erythrocyte. It can be concluded from the results that 270 kDa membrane protein of P. falciparum infected erythrocyte in complicated malaria patient might be a PfEMP-1. This protein can be detected by immunocytochemistry method using polyclonal antibody and can be used for the candidate of complicated malaria diagnostic   Keywords: Plasmodium falciparum, 270 kDA protein, immunocytochemistry, polyclonal antibody  

scholarly journals Serum Levels of the Proinflammatory Cytokines Interleukin-1 Beta (IL-1β), IL-6, IL-8, IL-10, Tumor Necrosis Factor Alpha, and IL-12(p70) in Malian Children with Severe Plasmodium falciparum Malaria and Matched Uncomplicated Malaria or Healthy Controls

2004 ◽  
Vol 72 (10) ◽  
pp. 5630-5637 ◽  
Author(s):  
K. E. Lyke ◽  
R. Burges ◽  
Y. Cissoko ◽  
L. Sangare ◽  
M. Dao ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Uncomplicated Malaria ◽  
Tumor Necrosis ◽  
Severe Anemia ◽  
Healthy Controls ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Inflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparum malaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P = <0.001), IL-10 (1,099.3 versus 14.1; P = <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P = <0.001), and IL-12(p70) (48.9 versus 31.3; P = 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P = <0.001) and IL-10 (1,099.3 versus 133.9; P = <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P = <0.001) and IL-10 (1,405.6 versus 868.6; P = 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P = 0.03) and IL-10 (391.1 versus 1,160.9; P = 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P = 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparum malaria.

scholarly journals DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

2013 ◽  
Vol 42 (4) ◽  
pp. 2270-2281 ◽  
Author(s):  
Adam F. Sander ◽  
Thomas Lavstsen ◽  
Thomas S. Rask ◽  
Michael Lisby ◽  
Ali Salanti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Gene Families ◽  
Secondary Structures ◽  
Erythrocyte Membrane Protein ◽  
Sexual Stages ◽  
Dna Secondary Structures ◽  
Parasitic Pathogens ◽  
Falciparum Erythrocyte Membrane Protein

Abstract Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens.

scholarly journals Identification of Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) as the Rosetting Ligand of the Malaria Parasite P. falciparum

1998 ◽  
Vol 187 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Qijun Chen ◽  
Antonio Barragan ◽  
Victor Fernandez ◽  
Annika Sundström ◽  
Martha Schlichtherle ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Heparan Sulfate ◽  
Erythrocyte Membrane ◽  
Plasmodium Falciparum Malaria ◽  
Glutathione S Transferase ◽  
Binding Motifs ◽  
Erythrocyte Membrane Protein ◽  
Adhesive Interactions ◽  
Falciparum Erythrocyte Membrane Protein

Severe Plasmodium falciparum malaria is characterized by excessive sequestration of infected and uninfected erythrocytes in the microvasculature of the affected organ. Rosetting, the adhesion of P. falciparum–infected erythrocytes to uninfected erythrocytes is a virulent parasite phenotype associated with the occurrence of severe malaria. Here we report on the identification by single-cell reverse transcriptase PCR and cDNA cloning of the adhesive ligand P. falciparum erythrocyte membrane protein 1 (PfEMP1). Rosetting PfEMP1 contains clusters of glycosaminoglycan-binding motifs. A recombinant fusion protein (Duffy binding-like 1–glutathione S transferase; Duffy binding-like-1–GST) was found to adhere directly to normal erythrocytes, disrupt naturally formed rosettes, block rosette reformation, and bind to a heparin-Sepharose matrix. The adhesive interactions could be inhibited with heparan sulfate or enzymes that remove heparan sulfate from the cell surface whereas other enzymes or similar glycosaminoglycans of a like negative charge did not affect the binding. PfEMP1 is suggested to be the rosetting ligand and heparan sulfate, or a heparan sulfate–like molecule, the receptor both for PfEMP1 binding and naturally formed erythrocyte rosettes.

Sign in / Sign up

Export Citation Format

Share Document