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

Research output: Contribution to journalArticleResearchpeer-review

3 Downloads (Pure)

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

Fingerprint

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.
@article{756b23e1b49d448e9d4d62d62f3970e5,
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",
month = "9",
day = "18",
doi = "10.1186/s12936-019-2962-0",
language = "English",
volume = "18",
pages = "1--11",
journal = "Malaria Journal",
issn = "1475-2875",
publisher = "BioMed Central",
number = "1",

}

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

IS - 1

M1 - 312

ER -