Severe adult malaria is associated with specific PfEMP1 adhesion types and high parasite biomass

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 23, 2016, Pages E3270-E3279

  Bernabeu, Maria ^a   Danziger, Samuel A ^a   Avril, Marion ^a   Vaz, Marina ^b   Babar, Prasad H ^c   Brazier, Andrew J ^a   Herricks, Thurston ^c   Maki, Jennifer N ^c   Pereira, Ligia ^c   Mascarenhas, Anjali ^c   Gomes, Edwin ^b   Chery, Laura ^c   Aitchison, John D ^a   Rathod, Pradipsinh K ^c   Smith, Joseph D ^a  

^a SEATTLE BIOMEDICAL RESEARCH INSTITUTE   (United States)

^b GOA MEDICAL COLLEGE   (India)

^c UNIVERSITY OF WASHINGTON   (United States)

Author keywords

EPCR; Malaria; PfEMP1; Plasmodium falciparum; Var

Indexed keywords

ENDOTHELIAL PROTEIN C RECEPTOR; ERYTHROCYTE MEMBRANE PROTEIN 1; CELL SURFACE RECEPTOR; ERYTHROCYTE MEMBRANE PROTEIN 1, PLASMODIUM FALCIPARUM; LEUKOCYTE ANTIGEN; PROCR PROTEIN, HUMAN; PROTEIN C; PROTOZOAL PROTEIN;

ADULT; ARTICLE; BINDING AFFINITY; BRAIN MALARIA; DISEASE ASSOCIATION; DISEASE SEVERITY; ENDOTHELIUM CELL; FEMALE; HOSPITALIZATION; HUMAN; HUMAN CELL; INDIA; MACHINE LEARNING; MAJOR CLINICAL STUDY; MALARIA; MALE; MICROBIAL BIOMASS; NONHUMAN; PARASITE LOAD; PARASITE VIRULENCE; PLASMODIUM FALCIPARUM; PRIORITY JOURNAL; BIOMASS; CHEMISTRY; GENETICS; MALARIA FALCIPARUM; METABOLISM; MIDDLE AGED; PARASITOLOGY; PATHOGENICITY; PROTEIN DOMAIN; VIRULENCE; YOUNG ADULT;

ADULT; ANTIGENS, CD; BIOMASS; FEMALE; HUMANS; MACHINE LEARNING; MALARIA, FALCIPARUM; MALE; MIDDLE AGED; PLASMODIUM FALCIPARUM; PROTEIN C; PROTEIN DOMAINS; PROTOZOAN PROTEINS; RECEPTORS, CELL SURFACE; VIRULENCE; YOUNG ADULT;

EID: 84973343099     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1524294113     Document Type: Article

References (64)

1. World Health Organization (2015) WHO World Malaria Report 2015. Avaliable at www.who.int/malaria/publications/world-malaria-report-2015/report/en/. Accessed February 2016.
2. Anonymous (2014) Severe malaria. Trop Med Int Health 19(Suppl 1):7-131.
3. White NJ, et al. (2014) Malaria. Lancet 383(9918):723-735.
4. Dondorp AM, et al. (2008) The relationship between age and the manifestations of and mortality associated with severe malaria. Clin Infect Dis 47(2): 151-157.
5. Miller LH, Baruch DI, Marsh K, Doumbo OK (2002) The pathogenic basis of malaria. Nature 415(6872):673-679.
6. Dondorp AM, et al. (2008) Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria. J Infect Dis 197(1):79-84.
7. Yeo TW, et al. (2008) Angiopoietin-2 is associated with decreased endothelial nitric oxide and poor clinical outcome in severe falciparum malaria. Proc Natl Acad Sci USA 105(44):17097-17102.
8. Baruch DI, et al. (1995) Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82(1):77-87.
9. Smith JD, et al. (1995) Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82(1):101-110.
10. Su XZ, et al. (1995) The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82(1):89-100.
11. Lavstsen T, Salanti A, Jensen AT, Arnot DE, Theander TG (2003) Sub-grouping of Plasmodium falciparum 3D7 var genes based on sequence analysis of coding and noncoding regions. Malar J 2(1):27.
12. Smith JD, Subramanian G, Gamain B, Baruch DI, Miller LH (2000) Classification of adhesive domains in the Plasmodium falciparum erythrocyte membrane protein 1 family. Mol Biochem Parasitol 110(2):293-310.
13. Rask TS, Hansen DA, Theander TG, Gorm Pedersen A, Lavstsen T (2010) Plasmodium falciparum erythrocyte membrane protein 1 diversity in seven genomes-Divide and conquer. PLOS Comput Biol 6(9):e1000933.
14. Kyriacou HM, et al. (2006) Differential var gene transcription in Plasmodium falciparum isolates from patients with cerebral malaria compared to hyperparasitaemia. Mol Biochem Parasitol 150(2):211-218.
15. Lavstsen T, et al. (2012) Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children. Proc Natl Acad Sci USA 109(26):E1791-E1800.
16. Rottmann M, et al. (2006) Differential expression of var gene groups is associated with morbidity caused by Plasmodium falciparum infection in Tanzanian children. Infect Immun 74(7):3904-3911.
17. Warimwe GM, et al. (2009) Plasmodium falciparum var gene expression is modified by host immunity. Proc Natl Acad Sci USA 106(51):21801-21806.
18. Warimwe GM, et al. (2012) Prognostic indicators of life-threatening malaria are associated with distinct parasite variant antigen profiles. Sci Transl Med 4(129):129ra45.
19. Bertin GI, et al. (2013) Expression of the domain cassette 8 Plasmodium falciparum erythrocyte membrane protein 1 is associated with cerebral malaria in Benin. PLoS One 8(7):e68368.
20. Carlson J, et al. (1990) Human cerebral malaria: Association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet 336(8729):1457-1460.
21. Ghumra A, et al. (2012) Induction of strain-transcending antibodies against Group A PfEMP1 surface antigens from virulent malaria parasites. PLoS Pathog 8(4): e1002665.
22. Kaul DK, Roth EF, Jr, Nagel RL, Howard RJ, Handunnetti SM (1991) Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions. Blood 78(3):812-819.
23. Turner L, et al. (2013) Severe malaria is associated with parasite binding to endothelial protein C receptor. Nature 498(7455):502-505.
24. Mosnier LO, Zlokovic BV, Griffin JH (2007) The cytoprotective protein C pathway. Blood 109(8):3161-3172.
25. Gillrie MR, et al. (2015) Diverse functional outcomes of Plasmodium falciparum ligation of EPCR: Potential implications for malarial pathogenesis. Cell Microbiol 17(12): 1883-1899.
26. Lau CK, et al. (2015) Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria. Cell Host Microbe 17(1):118-129.
27. Petersen JE, et al. (2015) Protein C system defects inflicted by the malaria parasite protein PfEMP1 can be overcome by a soluble EPCR variant. Thromb Haemost 114(5): 1038-1048.
28. Sampath S, et al. (2015) Plasmodium falciparum adhesion domains linked to severe malaria differ in blockade of endothelial protein C receptor. Cell Microbiol 17(12): 1868-1882.
29. Seydel KB, et al. (2015) Brain swelling and death in children with cerebral malaria. N Engl J Med 372(12):1126-1137.
30. Moxon CA, et al. (2013) Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children. Blood 122(5):842-851.
31. Dondorp AM, et al. (2005) Estimation of the total parasite biomass in acute falciparum malaria from plasma PfHRP2. PLoS Med 2(8):e204.
32. Hendriksen IC, et al. (2012) Diagnosing severe falciparum malaria in parasitaemic African children: A prospective evaluation of plasma PfHRP2 measurement. PLoS Med 9(8):e1001297.
33. Fox LL, et al. (2013) Histidine-rich protein 2 plasma levels predict progression to cerebral malaria in Malawian children with Plasmodium falciparum infection. J Infect Dis 208(3):500-503.
34. Seydel KB, et al. (2012) Plasma concentrations of parasite histidine-rich protein 2 distinguish between retinopathy-positive and retinopathy-negative cerebral malaria in Malawian children. J Infect Dis 206(3):309-318.
35. Hendriksen IC, et al. (2013) Defining falciparum-malaria-attributable severe febrile illness in moderate-to-high transmission settings on the basis of plasma PfHRP2 concentration. J Infect Dis 207(2):351-361.
36. Gonçalves BP, et al. (2014) Parasite burden and severity of malaria in Tanzanian children. N Engl J Med 370(19):1799-1808.
37. World Health Organization (2000) Severe falciparum malaria. World Health Organization, communicable diseases cluster. Trans R Soc Trop Med Hyg 94(Suppl 1):S1-S90.
38. Smith JD, Rowe JA, Higgins MK, Lavstsen T (2013) Malaria's deadly grip: Cytoadhesion of Plasmodium falciparum-infected erythrocytes. Cell Microbiol 15(12):1976-1983.
39. Liaw A, Wiener M (2002) Classification and regression by randomForest. R News 2(3): 18-22.
40. Huynh-Thu VA, Saeys Y, Wehenkel L, Geurts P (2012) Statistical interpretation of machine learning-based feature importance scores for biomarker discovery. Bioinformatics 28(13):1766-1774.
41. Finney OC, et al. (2014) Predicting antidisease immunity using proteome arrays and sera from children naturally exposed to malaria. Mol Cell Proteomics 13(10): 2646-2660.
42. Rowe JA, Claessens A, Corrigan RA, Arman M (2009) Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: Molecular mechanisms and therapeutic implications. Expert Rev Mol Med 11:e16.
43. Subudhi AK, et al. (2015) Plasmodium falciparum complicated malaria: Modulation and connectivity between exportome and variant surface antigen gene families. Mol Biochem Parasitol 201(1):31-46.
44. Cham GK, et al. (2009) Sequential, ordered acquisition of antibodies to Plasmodium falciparum erythrocyte membrane protein 1 domains. J Immunol 183(5):3356-3363.
45. Bachmann A, et al. (2011) Highly co-ordinated var gene expression and switching in clinical Plasmodium falciparum isolates from non-immune malaria patients. Cell Microbiol 13(9):1397-1409.
46. Abdi AI, et al. (2014) Plasmodium falciparum antigenic variation: Relationships between widespread endothelial activation, parasite PfEMP1 expression and severe malaria. BMC Infect Dis 14(1):170.
47. Dorovini-Zis K, et al. (2011) The neuropathology of fatal cerebral malaria in Malawian children. Am J Pathol 178(5):2146-2158.
48. Milner DA, Jr, et al. (2014) The systemic pathology of cerebral malaria in African children. Front Cell Infect Microbiol 4:104.
49. MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA (1985) Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol 119(3):385-401.
50. Spitz S (1946) The pathology of acute falciparum malaria. Mil Surg 99(5):555-572.
51. Brown H, et al. (1999) Evidence of blood-brain barrier dysfunction in human cerebral malaria. Neuropathol Appl Neurobiol 25(4):331-340.
52. Brown H, et al. (2001) Blood-brain barrier function in cerebral malaria in Malawian children. Am J Trop Med Hyg 64(3-4):207-213.
53. Avril M, Brazier AJ, Melcher M, Sampath S, Smith JD (2013) DC8 and DC13 var genes associated with severe malaria bind avidly to diverse endothelial cells. PLoS Pathog 9(6):e1003430.
54. Stevenson L, et al. (2015) α 2-Macroglobulin can crosslink multiple Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) molecules and may facilitate adhesion of parasitized erythrocytes. PLoS Pathog 11(7):e1005022.
55. Jeppesen A, et al. (2015) Multiple Plasmodium falciparum erythrocyte membrane protein 1 variants per genome can bind IgM via its Fc fragment Fcμ. Infect Immun 83(10):3972-3981.
56. Niang M, et al. (2014) STEVOR is a Plasmodium falciparum erythrocyte binding protein that mediates merozoite invasion and rosetting. Cell Host Microbe 16(1):81-93.
57. Goel S, et al. (2015) RIFINs are adhesins implicated in severe Plasmodium falciparum malaria. Nat Med 21(4):314-317.
58. Avril M, et al. (2012) A restricted subset of var genes mediates adherence of Plasmodium falciparum-infected erythrocytes to brain endothelial cells. Proc Natl Acad Sci USA 109(26):E1782-E1790.
59. Grubinger T, Zeileis A, Pfeiffer K-P (2014) evtree: Evolutionary learning of globally optimal classification and regression trees in R. Journal of Statistical Software, 61(1): 1-29.
60. Wyner AD (1978) A definition of conditional mutual information for arbitrary ensembles. Inf Control 38(1):51-59.
61. Fisher R (1921) On the «probable error» of a coefficient of correlation deduced from a small sample. Metron 1(Pt 4):1-32.
62. Bengtsson A, et al. (2013) A novel domain cassette identifies Plasmodium falciparum PfEMP1 proteins binding ICAM-1 and is a target of cross-reactive, adhesion-inhibitory antibodies. J Immunol 190(1):240-249.
63. Howell DPG, et al. (2008) Mapping a common interaction site used by Plasmodium falciparum Duffy binding-like domains to bind diverse host receptors. Mol Microbiol 67(1):78-87.
64. Oleinikov AV, et al. (2009) High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies. PLoS Pathog 5(4):e1000386.