Poster Presentation First Malaria World Congress 2018

Red blood cell complement regulatory proteins are lost during both vivax and falciparum malarial anaemia and are not associated with protective complement-fixing antibodies (#365)

Damian Oyong 1 2 , Enny Kenangalem 3 4 , Fiona Amante 5 , Fabian Rivera 5 , Christian Engwerda 5 6 , James McCarthy 5 6 , Rini Poespoprodjo 3 4 7 , James Beeson 8 9 10 , Nick Anstey 2 , Ric Price 2 11 , Michelle Boyle 2 8
  1. Charles Darwin University, Darwin, NT, Australia
  2. Menzies School of Health Research, Tiwi, NT, Australia
  3. Mimika District Health Authority, Timika, Papua, Indonesia
  4. Papuan Health and Community Development Foundation, Timika, Papua, Indonesia
  5. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
  6. School of Medicine, University of Queensland, Brisbane, QLD, Australia
  7. Department of Paediatrics, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Central Java, Indonesia
  8. Burnet Institute, Melbourne, Victoria, Australia
  9. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  10. Department of Microbiology and Central Clinical School, Monash University, Melbourne, VIC, Australia
  11. Centre for Tropical Medicine and Global Health, Department of Clinical Medicine, University of Oxford, Headington, Oxford, UK

Background

Anaemia is an important comorbidity of malaria, however, the mechanisms driving anaemia are unclear. Complement activation and loss of complement regulatory proteins (CRPs) on red blood cells (RBCs) has been identified to contribute to anaemia in Plasmodium falciparum infection, but its role in P. vivax is unknown. In contrast, antibodies that fix complement are major components in protective immunity against Plasmodium infection. We defined loss of CRPs in both P. falciparum and P. vivax anaemia, and determined if CRP loss was linked to complement-fixing antibodies.

Methods

RBCs from patients with P. falciparum (n=79) and P. vivax (n=42) malaria were collected from Papua, Indonesia, and from volunteers undergoing controlled human P. falciparum malaria infection (CHMI). Anaemia was categorised according to WHO criteria. Cytofluorometry was used to distinguish parasitised RBCs and to measure CRPs expression (CR1, CD55F, and CD59) on RBCs.  Complement activation (C3a and C5a) and parasite-specific complement-fixing antibodies was measured by ELISA.

Results

Expression of CR1 and CD55 were reduced in severe anaemia in both P. falciparum and P. vivax malaria. Reduction was restricted to uninfected RBCs, with infected RBC having higher levels of CRPs regardless of anaemia. CR1 and CD55 were also reduced in uninfected RBCs from volunteers during CHMI. There was no association between complement-fixing and CRPs RBC expression.

Conclusion

Our findings demonstrate the importance of reduced RBC CRPs expression in both P. falciparum and P. vivax malarial anaemia, and show that CRP loss is not linked to complement-fixing antibodies which have important role in malaria protection. Reduced CRPs was restricted to uninfected RBCs, likely contributing to the known vulnerability to destruction of the large uninfected RBC pool in malaria, and suggesting that parasites are relatively protected from complement-mediated destruction during infection. These findings provide clinically important insights into the pathogenesis of malaria anaemia.