Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria

Michael Duffy; Rintis Noviyanti; Takafumi Tsuboi; ZP Feng; Leily Trianty; Boni Sebayang; E Takashima; F Sumardy; Daniel Lampah; L Turner; Thomas Lavstsen; Freya J.I. Fowkes; Peter Siba; Stephen Rogerson; Thor Theander; Jutta Marfurt; Ric Price; Nicholas Anstey; Graham Brown; AT Papenfuss

doi:10.1186/s12936-016-1296-4

Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria

Michael Duffy, Rintis Noviyanti, Takafumi Tsuboi, ZP Feng, Leily Trianty, Boni Sebayang, E Takashima, F Sumardy, Daniel Lampah, L Turner, Thomas Lavstsen, Freya J.I. Fowkes, Peter Siba, Stephen Rogerson, Thor Theander, Jutta Marfurt, Ric Price, Nicholas Anstey, Graham Brown, AT Papenfuss

Global and Tropical Health

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Abstract

Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria.

Methods: Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.

Results: Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria.

Conclusion: These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.

Original language	English
Article number	258
Pages (from-to)	1-12
Number of pages	12
Journal	Malaria Journal
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s12936-016-1296-4
Publication status	Published - 2016

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Duffy, M., Noviyanti, R., Tsuboi, T., Feng, ZP., Trianty, L., Sebayang, B., Takashima, E., Sumardy, F., Lampah, D., Turner, L., Lavstsen, T., Fowkes, F. J. I., Siba, P., Rogerson, S., Theander, T., Marfurt, J., Price, R., Anstey, N., Brown, G., & Papenfuss, AT. (2016). Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria. Malaria Journal, 15(1), 1-12. [258]. https://doi.org/10.1186/s12936-016-1296-4

@article{d67d3d6bc44a413b8f535c641520f988,

title = "Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria",

abstract = "Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria. Methods: Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.Results: Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria. Conclusion: These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia. ",

author = "Michael Duffy and Rintis Noviyanti and Takafumi Tsuboi and ZP Feng and Leily Trianty and Boni Sebayang and E Takashima and F Sumardy and Daniel Lampah and L Turner and Thomas Lavstsen and Fowkes, {Freya J.I.} and Peter Siba and Stephen Rogerson and Thor Theander and Jutta Marfurt and Ric Price and Nicholas Anstey and Graham Brown and AT Papenfuss",

note = "National Health and Medical Research Council of Australia [Grant 1007954, Grant 513782] , National Health and Medical Research Council of Australia (Program Grant 1037304 awarded to RNP and NMA)",

year = "2016",

doi = "10.1186/s12936-016-1296-4",

language = "English",

volume = "15",

pages = "1--12",

journal = "Malaria Journal",

issn = "1475-2875",

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Duffy, M, Noviyanti, R, Tsuboi, T, Feng, ZP, Trianty, L, Sebayang, B, Takashima, E, Sumardy, F, Lampah, D, Turner, L, Lavstsen, T, Fowkes, FJI, Siba, P, Rogerson, S, Theander, T, Marfurt, J, Price, R , Anstey, N, Brown, G & Papenfuss, AT 2016, 'Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria', Malaria Journal, vol. 15, no. 1, 258, pp. 1-12. https://doi.org/10.1186/s12936-016-1296-4

TY - JOUR

T1 - Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria

AU - Duffy, Michael

AU - Noviyanti, Rintis

AU - Tsuboi, Takafumi

AU - Feng, ZP

AU - Trianty, Leily

AU - Sebayang, Boni

AU - Takashima, E

AU - Sumardy, F

AU - Lampah, Daniel

AU - Turner, L

AU - Lavstsen, Thomas

AU - Fowkes, Freya J.I.

AU - Siba, Peter

AU - Rogerson, Stephen

AU - Theander, Thor

AU - Marfurt, Jutta

AU - Price, Ric

AU - Anstey, Nicholas

AU - Brown, Graham

AU - Papenfuss, AT

N1 - National Health and Medical Research Council of Australia [Grant 1007954, Grant 513782] , National Health and Medical Research Council of Australia (Program Grant 1037304 awarded to RNP and NMA)

PY - 2016

Y1 - 2016

N2 - Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria. Methods: Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.Results: Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria. Conclusion: These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.

AB - Background: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria. Methods: Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured.Results: Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria. Conclusion: These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.

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U2 - 10.1186/s12936-016-1296-4

DO - 10.1186/s12936-016-1296-4

M3 - Article

C2 - 27149991

SN - 1475-2875

VL - 15

SP - 1

EP - 12

JO - Malaria Journal

JF - Malaria Journal

IS - 1

M1 - 258

ER -

Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria

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