Levels of human proteins in plasma associated with acute paediatric malaria
Abstract 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-11-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12936-018-2576-y |
| _version_ | 1828750096686120960 |
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| author | Philippa Reuterswärd Sofia Bergström Judy Orikiiriza Elisabeth Lindquist Sven Bergström Helene Andersson Svahn Burcu Ayoglu Mathias Uhlén Mats Wahlgren Johan Normark Ulf Ribacke Peter Nilsson |
| author_facet | Philippa Reuterswärd Sofia Bergström Judy Orikiiriza Elisabeth Lindquist Sven Bergström Helene Andersson Svahn Burcu Ayoglu Mathias Uhlén Mats Wahlgren Johan Normark Ulf Ribacke Peter Nilsson |
| author_sort | Philippa Reuterswärd |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T20:32:58Z |
| format | Article |
| id | doaj.art-e44f0d73c2b547fba6a3c1fa972c6182 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-10T20:32:58Z |
| publishDate | 2018-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-e44f0d73c2b547fba6a3c1fa972c61822022-12-22T01:34:38ZengBMCMalaria Journal1475-28752018-11-0117111910.1186/s12936-018-2576-yLevels of human proteins in plasma associated with acute paediatric malariaPhilippa Reuterswärd0Sofia Bergström1Judy Orikiiriza2Elisabeth Lindquist3Sven Bergström4Helene Andersson Svahn5Burcu Ayoglu6Mathias Uhlén7Mats Wahlgren8Johan Normark9Ulf Ribacke10Peter Nilsson11Department of Protein Science, SciLifeLab, KTH Royal Institute of TechnologyDepartment of Protein Science, SciLifeLab, KTH Royal Institute of TechnologyInfectious Diseases Institute, College of Health Sciences, Makerere UniversityDepartment of Molecular Biology, Umeå UniversityDepartment of Molecular Biology, Umeå UniversityDepartment of Protein Science, SciLifeLab, KTH Royal Institute of TechnologyDepartment of Protein Science, SciLifeLab, KTH Royal Institute of TechnologyDepartment of Protein Science, SciLifeLab, KTH Royal Institute of TechnologyDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Molecular Biology, Umeå UniversityDepartment of Microbiology, Tumor and Cell Biology, Karolinska InstitutetDepartment of Protein Science, SciLifeLab, KTH Royal Institute of TechnologyAbstract 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.http://link.springer.com/article/10.1186/s12936-018-2576-yAffinity proteomicsHuman plasma profilingMalariaPlasmodium falciparum, suspension bead arraysSequestrationCytoadhesion |
| spellingShingle | Philippa Reuterswärd Sofia Bergström Judy Orikiiriza Elisabeth Lindquist Sven Bergström Helene Andersson Svahn Burcu Ayoglu Mathias Uhlén Mats Wahlgren Johan Normark Ulf Ribacke Peter Nilsson Levels of human proteins in plasma associated with acute paediatric malaria Malaria Journal Affinity proteomics Human plasma profiling Malaria Plasmodium falciparum, suspension bead arrays Sequestration Cytoadhesion |
| title | Levels of human proteins in plasma associated with acute paediatric malaria |
| title_full | Levels of human proteins in plasma associated with acute paediatric malaria |
| title_fullStr | Levels of human proteins in plasma associated with acute paediatric malaria |
| title_full_unstemmed | Levels of human proteins in plasma associated with acute paediatric malaria |
| title_short | Levels of human proteins in plasma associated with acute paediatric malaria |
| title_sort | levels of human proteins in plasma associated with acute paediatric malaria |
| topic | Affinity proteomics Human plasma profiling Malaria Plasmodium falciparum, suspension bead arrays Sequestration Cytoadhesion |
| url | http://link.springer.com/article/10.1186/s12936-018-2576-y |
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