Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection

Damian A. Oyong, Jessica R. Loughland, Arya Sheelanair, Dean Andrew, Fabian D.L. Rivera, Kim A. Piera, Timothy William, Matthew J. Grigg, Bridget E. Barber, Ashraful Haque, Christian R. Engwerda, James S. McCarthy, Nicholas M. Anstey, Michelle J. Boyle

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    Abstract

    Background: Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection. 

    Methods: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated. 

    Results: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM. 

    Conclusions: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.

    Original languageEnglish
    Article number312
    Pages (from-to)1-11
    Number of pages11
    JournalMalaria Journal
    Volume18
    Issue number1
    DOIs
    Publication statusPublished - 18 Sep 2019

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    Plasmodium falciparum
    Malaria
    Anemia
    Complement System Proteins
    Erythrocytes
    Infection
    Plasmodium vivax
    Reticulocytes
    Hemoglobins
    Malaysia
    Volunteers
    Parasitemia
    Blood Circulation
    Complement Activation
    Population

    Cite this

    Oyong, D. A., Loughland, J. R., Sheelanair, A., Andrew, D., Rivera, F. D. L., Piera, K. A., ... Boyle, M. J. (2019). Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection. Malaria Journal, 18(1), 1-11. [312]. https://doi.org/10.1186/s12936-019-2962-0
    Oyong, Damian A. ; Loughland, Jessica R. ; Sheelanair, Arya ; Andrew, Dean ; Rivera, Fabian D.L. ; Piera, Kim A. ; William, Timothy ; Grigg, Matthew J. ; Barber, Bridget E. ; Haque, Ashraful ; Engwerda, Christian R. ; McCarthy, James S. ; Anstey, Nicholas M. ; Boyle, Michelle J. / Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection. In: Malaria Journal. 2019 ; Vol. 18, No. 1. pp. 1-11.
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    title = "Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection",
    abstract = "Background: Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection. Methods: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-na{\"i}ve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated. Results: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM. Conclusions: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.",
    keywords = "Anaemia, Complement, Complement regulatory proteins, falciparum, Malaria, vivax",
    author = "Oyong, {Damian A.} and Loughland, {Jessica R.} and Arya Sheelanair and Dean Andrew and Rivera, {Fabian D.L.} and Piera, {Kim A.} and Timothy William and Grigg, {Matthew J.} and Barber, {Bridget E.} and Ashraful Haque and Engwerda, {Christian R.} and McCarthy, {James S.} and Anstey, {Nicholas M.} and Boyle, {Michelle J.}",
    year = "2019",
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    language = "English",
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    Oyong, DA, Loughland, JR, Sheelanair, A, Andrew, D, Rivera, FDL, Piera, KA, William, T, Grigg, MJ, Barber, BE, Haque, A, Engwerda, CR, McCarthy, JS, Anstey, NM & Boyle, MJ 2019, 'Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection', Malaria Journal, vol. 18, no. 1, 312, pp. 1-11. https://doi.org/10.1186/s12936-019-2962-0

    Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection. / Oyong, Damian A.; Loughland, Jessica R.; Sheelanair, Arya; Andrew, Dean; Rivera, Fabian D.L.; Piera, Kim A.; William, Timothy; Grigg, Matthew J.; Barber, Bridget E.; Haque, Ashraful; Engwerda, Christian R.; McCarthy, James S.; Anstey, Nicholas M.; Boyle, Michelle J.

    In: Malaria Journal, Vol. 18, No. 1, 312, 18.09.2019, p. 1-11.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Loss of complement regulatory proteins on red blood cells in mild malarial anaemia and in Plasmodium falciparum induced blood-stage infection

    AU - Oyong, Damian A.

    AU - Loughland, Jessica R.

    AU - Sheelanair, Arya

    AU - Andrew, Dean

    AU - Rivera, Fabian D.L.

    AU - Piera, Kim A.

    AU - William, Timothy

    AU - Grigg, Matthew J.

    AU - Barber, Bridget E.

    AU - Haque, Ashraful

    AU - Engwerda, Christian R.

    AU - McCarthy, James S.

    AU - Anstey, Nicholas M.

    AU - Boyle, Michelle J.

    PY - 2019/9/18

    Y1 - 2019/9/18

    N2 - Background: Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection. Methods: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated. Results: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM. Conclusions: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.

    AB - Background: Anaemia is a major consequence of malaria, caused by the removal of both infected and uninfected red blood cells (RBCs) from the circulation. Complement activation and reduced expression of complement regulatory proteins (CRPs) on RBCs are an important pathogenic mechanism in severe malarial anaemia in both Plasmodium falciparum and Plasmodium vivax infection. However, little is known about loss of CRPs on RBCs during mild malarial anaemia and in low-density infection. Methods: The expression of CRP CR1, CD55, CD59, and the phagocytic regulator CD47, on uninfected normocytes and reticulocytes were assessed in individuals from two study populations: (1) P. falciparum and P. vivax-infected patients from a low transmission setting in Sabah, Malaysia; and, (2) malaria-naïve volunteers undergoing P. falciparum induced blood-stage malaria (IBSM). For clinical infections, individuals were categorized into anaemia severity categories based on haemoglobin levels. For IBSM, associations between CRPs and haemoglobin level were investigated. Results: CRP expression on RBC was lower in Malaysian individuals with P. falciparum and P. vivax mild malarial anaemia compared to healthy controls. CRP expression was also reduced on RBCs from volunteers during IBSM. Reduction occurred on normocytes and reticulocytes. However, there was no significant association between reduced CRPs and haemoglobin during IBSM. Conclusions: Removal of CRPs occurs on both RBCs and reticulocytes during Plasmodium infection even in mild malarial anaemia and at low levels of parasitaemia.

    KW - Anaemia

    KW - Complement

    KW - Complement regulatory proteins

    KW - falciparum

    KW - Malaria

    KW - vivax

    UR - http://www.scopus.com/inward/record.url?scp=85072384473&partnerID=8YFLogxK

    U2 - 10.1186/s12936-019-2962-0

    DO - 10.1186/s12936-019-2962-0

    M3 - Article

    VL - 18

    SP - 1

    EP - 11

    JO - Malaria Journal

    JF - Malaria Journal

    SN - 1475-2875

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