Binding of human serum proteins to P. falciparum-infected erythrocytes and its association with malaria clinical presentation

Abstract BackgroundThe pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2‑macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here.MethodsChildren 1-12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients.ResultsClinical data from 108 children classified as UM (n=54) and SM cases (n=54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n=14) and SM (n=20) children were analysed. Most of the field isolates bound non‑immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum.ConclusionsThe results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.

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Binding of human serum proteins to Plasmodium falciparum-infected erythrocytes and its association with malaria clinical presentation

10.21203/rs.3.rs-48813/v3 ◽

2020 ◽

Author(s):

Mary Lopez-Perez ◽

William van der Puije ◽

Filip C. Castberg ◽

Michael F. Ofori ◽

Lars Hviid

Keyword(s):

Human Serum ◽

Severe Malaria ◽

Clinical Presentation ◽

Serum Proteins ◽

Clinical Malaria ◽

Rosette Formation ◽

Parasite Protein ◽

Serum Factors ◽

Field Isolates ◽

Malaria Severity

Abstract Background The pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2‑macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here.Methods Children 1-12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients.Results Clinical data from 108 children classified as UM (n=54) and SM cases (n=54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n=14) and SM (n=20) children were analysed. Most of the field isolates bound non‑immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum. Conclusions The results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.

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Binding of human serum proteins to Plasmodium falciparum-infected erythrocytes and its association with malaria clinical presentation

Malaria Journal ◽

10.1186/s12936-020-03438-8 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Mary Lopez-Perez ◽

William van der Puije ◽

Filip C. Castberg ◽

Michael F. Ofori ◽

Lars Hviid

Keyword(s):

Plasmodium Falciparum ◽

Human Serum ◽

Severe Malaria ◽

Clinical Presentation ◽

Serum Proteins ◽

Rosette Formation ◽

Parasite Protein ◽

Serum Factors ◽

Field Isolates ◽

Malaria Severity

Abstract Background The pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2-macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here. Methods Children 1–12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients. Results Clinical data from 108 children classified as UM (n = 54) and SM cases (n = 54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n = 14) and SM (n = 20) children were analysed. Most of the field isolates bound non-immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum. Conclusions The results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.

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Binding of Human Serum Proteins to P. Falciparum Infected Erythrocytes and Its Association With Malaria Clinical Presentation

10.21203/rs.3.rs-48813/v1 ◽

2020 ◽

Author(s):

Mary Lopez-Perez ◽

William van der Puije ◽

Filip C. Castberg ◽

Michael F. Ofori ◽

Lars Hviid

Keyword(s):

Human Serum ◽

Severe Malaria ◽

Falciparum Malaria ◽

Clinical Presentation ◽

Serum Proteins ◽

Rosette Formation ◽

Parasite Protein ◽

Serum Factors ◽

Field Isolates ◽

Malaria Severity

Abstract Background The pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α 2 ‑macroglobulin (α 2 M), to increase the avidity of PfEMP1-mediated binding to host receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here. Methods Children between 1-12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α 2 M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α 2 M was also evaluated. Experimental results were related to the clinical presentation of the patients. Results Clinical data from 108 children classified as UM (n=54) and SM cases (n=54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from 34 children were analysed. Most of the field isolates bound non‑immune IgM (33/34), whereas the α 2 M-binding was less common (23/34) and mostly low. Binding of both non-immune IgM and α 2 M was higher in IEs from children with SM than from UM. In combination, IgM and α 2 M supported rosette formation at levels similar to that observed in the presence of 10% human serum. Conclusions The results support the hypothesis that binding of non-immune IgM and/or α 2 M to IEs facilitates rosette formation and contributes to P. falciparum malaria severity.

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INTERFERENCE BY SERUM PROTEINS WITH LH RADIOIMMUNOASSAY USING IMMUNOSORBENT

Acta Endocrinologica ◽

10.1530/acta.0.0720235 ◽

1973 ◽

Vol 72 (2) ◽

pp. 235-242 ◽

Cited By ~ 11

Author(s):

A. M. Reuter ◽

J. C. Hendrick ◽

J. Sulon ◽

P. Franchimont

Keyword(s):

Molecular Weight ◽

Human Serum ◽

High Molecular Weight ◽

Serum Proteins ◽

Void Volume ◽

High Molecular Weight Proteins ◽

Serum Fractionation ◽

Covalently Bound

ABSTRACT The percentage of LH* bound to antibodies that have been covalently bound to cellulose is diminished in the presence of LH-free human serum and sera from various species of animals. Serum fractionation studies on Sephadex G 200 show that the greatest interference comes from the proteins eluted in the void volume i. e. the high molecular weight proteins. Specifically, the gamma M globulins and the α2-macroglobulins appear to play an important role, as demonstrated by tests in which these proteins were neutralized by gamma M and α2-macroglobulin antisera.

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TESTOSTERONE BINDING BY HUMAN SERUM PROTEINS

Acta Endocrinologica ◽

10.1530/acta.0.067s105 ◽

1971 ◽

Vol 68 (1_Supplb) ◽

pp. S105 ◽

Cited By ~ 1

Author(s):

O. A. Lea ◽

K. F. Støa

Keyword(s):

Human Serum ◽

Serum Proteins ◽

Human Serum Proteins

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Faculty Opinions recommendation of Diagnosis, clinical presentation, and in-hospital mortality of severe malaria in HIV-coinfected children and adults in Mozambique.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717953479.793460562 ◽

2012 ◽

Author(s):

Susan Coffin

Keyword(s):

Hospital Mortality ◽

Severe Malaria ◽

Clinical Presentation

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Rapid Separation of Human Serum Proteins by Microchip Electrophoresis

CHINESE JOURNAL OF ANALYTICAL CHEMISTRY (CHINESE VERSION) ◽

10.3724/sp.j.1096.2012.11207 ◽

2013 ◽

Vol 40 (7) ◽

pp. 1118-1122

Author(s):

Zhong-Qi XU ◽

Hui-Qing LIU

Keyword(s):

Human Serum ◽

Serum Proteins ◽

Microchip Electrophoresis ◽

Rapid Separation ◽

Human Serum Proteins

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A Peptide Found in Human Serum, Derived from the C-Terminus of Albumin, Shows Antifungal Activity In Vitro and In Vivo

Microorganisms ◽

10.3390/microorganisms8101627 ◽

2020 ◽

Vol 8 (10) ◽

pp. 1627

Author(s):

Tecla Ciociola ◽

Pier Paolo Zanello ◽

Tiziana D’Adda ◽

Serena Galati ◽

Stefania Conti ◽

...

Keyword(s):

Antifungal Activity ◽

Human Serum ◽

Fungicidal Activity ◽

Galleria Mellonella ◽

Serum Proteins ◽

Morphological Alterations ◽

C Terminus ◽

Different Sources

The growing problem of antimicrobial resistance highlights the need for alternative strategies to combat infections. From this perspective, there is a considerable interest in natural molecules obtained from different sources, which are shown to be active against microorganisms, either alone or in association with conventional drugs. In this paper, peptides with the same sequence of fragments, found in human serum, derived from physiological proteins, were evaluated for their antifungal activity. A 13-residue peptide, representing the 597–609 fragment within the albumin C-terminus, was proved to exert a fungicidal activity in vitro against pathogenic yeasts and a therapeutic effect in vivo in the experimental model of candidal infection in Galleria mellonella. Studies by confocal microscopy and transmission and scanning electron microscopy demonstrated that the peptide penetrates and accumulates in Candida albicans cells, causing gross morphological alterations in cellular structure. These findings add albumin to the group of proteins, which already includes hemoglobin and antibodies, that could give rise to cryptic antimicrobial fragments, and could suggest their role in anti-infective homeostasis. The study of bioactive fragments from serum proteins could open interesting perspectives for the development of new antimicrobial molecules derived by natural sources.

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