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Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

Ray S, Patel SK, Venkatesh A, Bhave A, Kumar V, Singh V, Chatterjee G, Shah VG, Sharma S, Renu D, Nafis N, Gandhe P, Gogtay N, Thatte U, Sehgal K, Verma S, Karak A, Khanra D, Talukdar A, Kochar SK, S B V, Kochar DK, Rojh D, Varma SG, Gandhi MN, Srikanth R, Patankar S, Srivastava S - Sci Rep (2016)

Bottom Line: In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure.Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection.Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

ABSTRACT
In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the experimental strategy used for comparative analysis of serum proteome alterations in NSVM and SVM patients.(Drawn by the authors: S.R., S.K.P. and A.V).
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f1: Schematic representation of the experimental strategy used for comparative analysis of serum proteome alterations in NSVM and SVM patients.(Drawn by the authors: S.R., S.K.P. and A.V).

Mentions: In this study serum samples from non-severe (uncomplicated) vivax malaria (NSVM) and severe vivax malaria (SVM) patients along with healthy community controls (HC) and two other febrile infectious diseases, dengue fever (DF) and leptospirosis (LEP) from three different endemic regions of India were investigated. 2D-differential in gel electrophoresis (2D-DIGE) and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics in combination with electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) and Q-Exactive mass spectrometry platforms were used in the discovery phase of the study and selected targets were validated by enzyme-linked immunosorbent assay (ELISA) (Fig. 1). Quite a few differentially abundant proteins such as Haptoglobin (HP), Superoxide dismutase (SOD), Ceruloplasmin (CP), Titin (TTN), Nebulin (NEB), and Vitronectin (VTN) were found to be highly relevant in context of pathophysiology of severe malaria. Subsequent, bioinformatic analysis indicated that the identified differentially abundant proteins are associated with different vital physiological pathways including cytokine signaling, acute phase response, lipid metabolism, oxidative stress and anti-oxidative pathways, cytoskeletal regulation and complement cascades. Comprehensive quantitative proteomics and clinicopathological analysis of patients with different severity levels of the infection may enhance our understanding regarding pathogenesis of SVM and help to facilitate the clinical diagnosis of different severe malaria-associated symptoms in future.


Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

Ray S, Patel SK, Venkatesh A, Bhave A, Kumar V, Singh V, Chatterjee G, Shah VG, Sharma S, Renu D, Nafis N, Gandhe P, Gogtay N, Thatte U, Sehgal K, Verma S, Karak A, Khanra D, Talukdar A, Kochar SK, S B V, Kochar DK, Rojh D, Varma SG, Gandhi MN, Srikanth R, Patankar S, Srivastava S - Sci Rep (2016)

Schematic representation of the experimental strategy used for comparative analysis of serum proteome alterations in NSVM and SVM patients.(Drawn by the authors: S.R., S.K.P. and A.V).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835765&req=5

f1: Schematic representation of the experimental strategy used for comparative analysis of serum proteome alterations in NSVM and SVM patients.(Drawn by the authors: S.R., S.K.P. and A.V).
Mentions: In this study serum samples from non-severe (uncomplicated) vivax malaria (NSVM) and severe vivax malaria (SVM) patients along with healthy community controls (HC) and two other febrile infectious diseases, dengue fever (DF) and leptospirosis (LEP) from three different endemic regions of India were investigated. 2D-differential in gel electrophoresis (2D-DIGE) and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics in combination with electrospray ionization quadrupole time-of-flight (ESI-Q-TOF) and Q-Exactive mass spectrometry platforms were used in the discovery phase of the study and selected targets were validated by enzyme-linked immunosorbent assay (ELISA) (Fig. 1). Quite a few differentially abundant proteins such as Haptoglobin (HP), Superoxide dismutase (SOD), Ceruloplasmin (CP), Titin (TTN), Nebulin (NEB), and Vitronectin (VTN) were found to be highly relevant in context of pathophysiology of severe malaria. Subsequent, bioinformatic analysis indicated that the identified differentially abundant proteins are associated with different vital physiological pathways including cytokine signaling, acute phase response, lipid metabolism, oxidative stress and anti-oxidative pathways, cytoskeletal regulation and complement cascades. Comprehensive quantitative proteomics and clinicopathological analysis of patients with different severity levels of the infection may enhance our understanding regarding pathogenesis of SVM and help to facilitate the clinical diagnosis of different severe malaria-associated symptoms in future.

Bottom Line: In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure.Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection.Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.

ABSTRACT
In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

No MeSH data available.


Related in: MedlinePlus