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Levels of human proteins in plasma associated with acute paediatric malaria
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0003-0344-8049
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
Makerere Univ, Coll Hlth Sci, Infect Dis Inst, Kampala, Uganda..
Umeå Univ, Dept Mol Biol, Umeå, Sweden..
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2018 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 17, article id 426Article in journal (Refereed) Published
Abstract [en]

Background: The intimate interaction between the pathophysiology of the human host and the biology of the Plasmodium falciparum parasite results in a wide spectrum of disease outcomes in malaria. Development of severe disease is associated with a progressively augmented imbalance in pro- and anti-inflammatory responses to high parasite loads and sequestration of parasitized erythrocytes. Although these phenomena collectively constitute common denominators for the wide variety of discrete severe malaria manifestations, the mechanistic rationales behind discrepancies in outcome are poorly understood. Exploration of the human pathophysiological response by variations in protein profiles in plasma presents an excellent opportunity to increase the understanding. This is ultimately required for better prediction, prevention and treatment of malaria, which is essential for ongoing elimination and eradication efforts. Results: An affinity proteomics approach was used to analyse 541 paediatric plasma samples collected from community controls and patients with mild or severe malaria in Rwanda. Protein profiles were generated with an antibody-based suspension bead array containing 255 antibodies targetting 115 human proteins. Here, 57 proteins were identified with significantly altered levels (adjusted p-values<0.001) in patients with malaria compared to controls. From these, the 27 most significant proteins (adjusted p-values<10(-14)) were selected for a stringent analysis approach. Here, 24 proteins showed elevated levels in malaria patients and included proteins involved in acute inflammatory response as well as cell adhesion. The remaining three proteins, also implicated in immune regulation and cellular adhesivity, displayed lower abundance in malaria patients. In addition, 37 proteins (adjusted p-values<0.05) were identified with increased levels in patients with severe compared to mild malaria. This set includes, proteins involved in tissue remodelling and erythrocyte membrane proteins. Collectively, this approach has been successfully used to identify proteins both with known and unknown association with different stages of malaria. Conclusion: In this study, a high-throughput affinity proteomics approach was used to find protein profiles in plasma linked to P. falciparum infection and malaria disease progression. The proteins presented herein are mainly involved in inflammatory response, cellular adhesion and as constituents of erythrocyte membrane. These findings have a great potential to provide increased conceptual understanding of host-parasite interaction and malaria pathogenesis.

Place, publisher, year, edition, pages
BMC , 2018. Vol. 17, article id 426
Keywords [en]
Affinity proteomics, Human plasma profiling, Malaria, Plasmodium falciparum, suspension bead arrays, Sequestration, Cytoadhesion
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-239769DOI: 10.1186/s12936-018-2576-yISI: 000450509700002PubMedID: 30442134Scopus ID: 2-s2.0-85056636195OAI: oai:DiVA.org:kth-239769DiVA, id: diva2:1277087
Note

QC 20190109

Available from: 2019-01-09 Created: 2019-01-09 Last updated: 2019-01-09Bibliographically approved

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Reuterswärd, PhilippaBergström, SofiaSvahn Andersson, HeleneAyoglu, BurcuUhlén, MathiasNilsson, Peter

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