IgM in human immunity to Plasmodium falciparum malaria

M. J. Boyle, J. A. Chan, I. Handayuni, L. Reiling, G. Feng, A. Hilton, L. Kurtovic, D. Oyong, K. A. Piera, B. E. Barber, T. William, D. P. Eisen, G. Minigo, C. Langer, D. R. Drew, F. de Labastida Rivera, F. H. Amante, T. N. Williams, S. Kinyanjui, K. Marsh & 8 others D. L. Doolan, C. Engwerda, F. J.I. Fowkes, M. J. Grigg, I. Mueller, J. S. McCarthy, N. M. Anstey, J. G. Beeson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Most studies on human immunity to malaria have focused on the roles of immunoglobulin G (IgG), whereas the roles of IgM remain undefined. Analyzing multiple human cohorts to assess the dynamics of malaria-specific IgM during experimentally induced and naturally acquired malaria, we identified IgM activity against blood-stage parasites. We found that merozoite-specific IgM appears rapidly in Plasmodium falciparum infection and is prominent during malaria in children and adults with lifetime exposure, together with IgG. Unexpectedly, IgM persisted for extended periods of time; we found no difference in decay of merozoite-specific IgM over time compared to that of IgG. IgM blocked merozoite invasion of red blood cells in a complement-dependent manner. IgM was also associated with significantly reduced risk of clinical malaria in a longitudinal cohort of children. These findings suggest that merozoite-specific IgM is an important functional and long-lived antibody response targeting blood-stage malaria parasites that contributes to malaria immunity.

Original languageEnglish
Article numbereaax4489
Pages (from-to)1-14
Number of pages14
JournalScience Advances
Volume5
Issue number9
DOIs
Publication statusPublished - Sep 2019

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parasites
immunity
blood
erythrocytes
infectious diseases
antibodies
complement
life (durability)
decay

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Boyle, M. J., Chan, J. A., Handayuni, I., Reiling, L., Feng, G., Hilton, A., ... Beeson, J. G. (2019). IgM in human immunity to Plasmodium falciparum malaria. Science Advances, 5(9), 1-14. [eaax4489]. https://doi.org/10.1126/sciadv.aax4489
Boyle, M. J. ; Chan, J. A. ; Handayuni, I. ; Reiling, L. ; Feng, G. ; Hilton, A. ; Kurtovic, L. ; Oyong, D. ; Piera, K. A. ; Barber, B. E. ; William, T. ; Eisen, D. P. ; Minigo, G. ; Langer, C. ; Drew, D. R. ; de Labastida Rivera, F. ; Amante, F. H. ; Williams, T. N. ; Kinyanjui, S. ; Marsh, K. ; Doolan, D. L. ; Engwerda, C. ; Fowkes, F. J.I. ; Grigg, M. J. ; Mueller, I. ; McCarthy, J. S. ; Anstey, N. M. ; Beeson, J. G. / IgM in human immunity to Plasmodium falciparum malaria. In: Science Advances. 2019 ; Vol. 5, No. 9. pp. 1-14.
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title = "IgM in human immunity to Plasmodium falciparum malaria",
abstract = "Most studies on human immunity to malaria have focused on the roles of immunoglobulin G (IgG), whereas the roles of IgM remain undefined. Analyzing multiple human cohorts to assess the dynamics of malaria-specific IgM during experimentally induced and naturally acquired malaria, we identified IgM activity against blood-stage parasites. We found that merozoite-specific IgM appears rapidly in Plasmodium falciparum infection and is prominent during malaria in children and adults with lifetime exposure, together with IgG. Unexpectedly, IgM persisted for extended periods of time; we found no difference in decay of merozoite-specific IgM over time compared to that of IgG. IgM blocked merozoite invasion of red blood cells in a complement-dependent manner. IgM was also associated with significantly reduced risk of clinical malaria in a longitudinal cohort of children. These findings suggest that merozoite-specific IgM is an important functional and long-lived antibody response targeting blood-stage malaria parasites that contributes to malaria immunity.",
author = "Boyle, {M. J.} and Chan, {J. A.} and I. Handayuni and L. Reiling and G. Feng and A. Hilton and L. Kurtovic and D. Oyong and Piera, {K. A.} and Barber, {B. E.} and T. William and Eisen, {D. P.} and G. Minigo and C. Langer and Drew, {D. R.} and {de Labastida Rivera}, F. and Amante, {F. H.} and Williams, {T. N.} and S. Kinyanjui and K. Marsh and Doolan, {D. L.} and C. Engwerda and Fowkes, {F. J.I.} and Grigg, {M. J.} and I. Mueller and McCarthy, {J. S.} and Anstey, {N. M.} and Beeson, {J. G.}",
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Boyle, MJ, Chan, JA, Handayuni, I, Reiling, L, Feng, G, Hilton, A, Kurtovic, L, Oyong, D, Piera, KA, Barber, BE, William, T, Eisen, DP, Minigo, G, Langer, C, Drew, DR, de Labastida Rivera, F, Amante, FH, Williams, TN, Kinyanjui, S, Marsh, K, Doolan, DL, Engwerda, C, Fowkes, FJI, Grigg, MJ, Mueller, I, McCarthy, JS, Anstey, NM & Beeson, JG 2019, 'IgM in human immunity to Plasmodium falciparum malaria', Science Advances, vol. 5, no. 9, eaax4489, pp. 1-14. https://doi.org/10.1126/sciadv.aax4489

IgM in human immunity to Plasmodium falciparum malaria. / Boyle, M. J.; Chan, J. A.; Handayuni, I.; Reiling, L.; Feng, G.; Hilton, A.; Kurtovic, L.; Oyong, D.; Piera, K. A.; Barber, B. E.; William, T.; Eisen, D. P.; Minigo, G.; Langer, C.; Drew, D. R.; de Labastida Rivera, F.; Amante, F. H.; Williams, T. N.; Kinyanjui, S.; Marsh, K.; Doolan, D. L.; Engwerda, C.; Fowkes, F. J.I.; Grigg, M. J.; Mueller, I.; McCarthy, J. S.; Anstey, N. M.; Beeson, J. G.

In: Science Advances, Vol. 5, No. 9, eaax4489, 09.2019, p. 1-14.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - IgM in human immunity to Plasmodium falciparum malaria

AU - Boyle, M. J.

AU - Chan, J. A.

AU - Handayuni, I.

AU - Reiling, L.

AU - Feng, G.

AU - Hilton, A.

AU - Kurtovic, L.

AU - Oyong, D.

AU - Piera, K. A.

AU - Barber, B. E.

AU - William, T.

AU - Eisen, D. P.

AU - Minigo, G.

AU - Langer, C.

AU - Drew, D. R.

AU - de Labastida Rivera, F.

AU - Amante, F. H.

AU - Williams, T. N.

AU - Kinyanjui, S.

AU - Marsh, K.

AU - Doolan, D. L.

AU - Engwerda, C.

AU - Fowkes, F. J.I.

AU - Grigg, M. J.

AU - Mueller, I.

AU - McCarthy, J. S.

AU - Anstey, N. M.

AU - Beeson, J. G.

PY - 2019/9

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N2 - Most studies on human immunity to malaria have focused on the roles of immunoglobulin G (IgG), whereas the roles of IgM remain undefined. Analyzing multiple human cohorts to assess the dynamics of malaria-specific IgM during experimentally induced and naturally acquired malaria, we identified IgM activity against blood-stage parasites. We found that merozoite-specific IgM appears rapidly in Plasmodium falciparum infection and is prominent during malaria in children and adults with lifetime exposure, together with IgG. Unexpectedly, IgM persisted for extended periods of time; we found no difference in decay of merozoite-specific IgM over time compared to that of IgG. IgM blocked merozoite invasion of red blood cells in a complement-dependent manner. IgM was also associated with significantly reduced risk of clinical malaria in a longitudinal cohort of children. These findings suggest that merozoite-specific IgM is an important functional and long-lived antibody response targeting blood-stage malaria parasites that contributes to malaria immunity.

AB - Most studies on human immunity to malaria have focused on the roles of immunoglobulin G (IgG), whereas the roles of IgM remain undefined. Analyzing multiple human cohorts to assess the dynamics of malaria-specific IgM during experimentally induced and naturally acquired malaria, we identified IgM activity against blood-stage parasites. We found that merozoite-specific IgM appears rapidly in Plasmodium falciparum infection and is prominent during malaria in children and adults with lifetime exposure, together with IgG. Unexpectedly, IgM persisted for extended periods of time; we found no difference in decay of merozoite-specific IgM over time compared to that of IgG. IgM blocked merozoite invasion of red blood cells in a complement-dependent manner. IgM was also associated with significantly reduced risk of clinical malaria in a longitudinal cohort of children. These findings suggest that merozoite-specific IgM is an important functional and long-lived antibody response targeting blood-stage malaria parasites that contributes to malaria immunity.

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DO - 10.1126/sciadv.aax4489

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Boyle MJ, Chan JA, Handayuni I, Reiling L, Feng G, Hilton A et al. IgM in human immunity to Plasmodium falciparum malaria. Science Advances. 2019 Sep;5(9):1-14. eaax4489. https://doi.org/10.1126/sciadv.aax4489