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

Michael F Duffy; Rintis Noviyanti; Takafumi Tsuboi; Zhi-Ping Feng; Leily Trianty; Boni F Sebayang; Eizo Takashima; Fransisca Sumardy; Daniel A Lampah; Louise Turner; Thomas Lavstsen; Freya J I Fowkes; Peter Siba; Stephen J Rogerson; Thor G Theander; Jutta Marfurt; Ric N Price; Nicholas M Anstey; Graham V Brown; Anthony T Papenfuss

doi:10.1186/s12936-016-1296-4

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

Michael F Duffy, Rintis Noviyanti, Takafumi Tsuboi, Zhi-Ping Feng, Leily Trianty, Boni F Sebayang, Eizo Takashima, Fransisca Sumardy, Daniel A Lampah, Louise Turner, Thomas Lavstsen, Freya J I Fowkes, Peter Siba, Stephen J Rogerson, Thor G Theander, Jutta Marfurt, Ric N Price, Nicholas M Anstey, Graham V Brown, Anthony T Papenfuss

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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
Journal	Malaria Journal
Volume	15
Number of pages	12
ISSN	1475-2875
DOIs	https://doi.org/10.1186/s12936-016-1296-4
Publication status	Published - 5 May 2016

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Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malariaFinal published version, 1.05 MBLicence: CC BY

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

Duffy, MF, Noviyanti, R, Tsuboi, T, Feng, Z-P, Trianty, L, Sebayang, BF, Takashima, E, Sumardy, F, Lampah, DA, Turner, L , Lavstsen, T, Fowkes, FJI, Siba, P, Rogerson, SJ, Theander, TG, Marfurt, J, Price, RN, Anstey, NM, Brown, GV & Papenfuss, AT 2016, 'Differences in PfEMP1s recognized by antibodies from patients with uncomplicated or severe malaria', Malaria Journal, vol. 15, 258. https://doi.org/10.1186/s12936-016-1296-4

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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 = "Duffy, {Michael F} and Rintis Noviyanti and Takafumi Tsuboi and Zhi-Ping Feng and Leily Trianty and Sebayang, {Boni F} and Eizo Takashima and Fransisca Sumardy and Lampah, {Daniel A} and Louise Turner and Thomas Lavstsen and Fowkes, {Freya J I} and Peter Siba and Rogerson, {Stephen J} and Theander, {Thor G} and Jutta Marfurt and Price, {Ric N} and Anstey, {Nicholas M} and Brown, {Graham V} and Papenfuss, {Anthony T}",

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

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

AU - Duffy, Michael F

AU - Noviyanti, Rintis

AU - Tsuboi, Takafumi

AU - Feng, Zhi-Ping

AU - Trianty, Leily

AU - Sebayang, Boni F

AU - Takashima, Eizo

AU - Sumardy, Fransisca

AU - Lampah, Daniel A

AU - Turner, Louise

AU - Lavstsen, Thomas

AU - Fowkes, Freya J I

AU - Siba, Peter

AU - Rogerson, Stephen J

AU - Theander, Thor G

AU - Marfurt, Jutta

AU - Price, Ric N

AU - Anstey, Nicholas M

AU - Brown, Graham V

AU - Papenfuss, Anthony T

PY - 2016/5/5

Y1 - 2016/5/5

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.

U2 - 10.1186/s12936-016-1296-4

DO - 10.1186/s12936-016-1296-4

M3 - Journal article

C2 - 27149991

SN - 1475-2875

VL - 15

JO - Malaria Journal

JF - Malaria Journal

M1 - 258

ER -

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

Abstract

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