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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

ELISA-based validation of differentially abundant proteins.(A) Determination of serum levels of 11 differentially abundant proteins (identified in the discovery phase of the study) in HC (n = 103), NSVM (n = 118), and SVM (n = 34) by ELISA. **indicates p < 0.001, *indicates 0.001 < p < 0.05 and NS indicates p > 0.05 based on a Mann-Whitney U test. (B) ROC curves depicting accuracy of different serum proteins for prediction of NSVM and SVM.
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f4: ELISA-based validation of differentially abundant proteins.(A) Determination of serum levels of 11 differentially abundant proteins (identified in the discovery phase of the study) in HC (n = 103), NSVM (n = 118), and SVM (n = 34) by ELISA. **indicates p < 0.001, *indicates 0.001 < p < 0.05 and NS indicates p > 0.05 based on a Mann-Whitney U test. (B) ROC curves depicting accuracy of different serum proteins for prediction of NSVM and SVM.

Mentions: Compared to HC, both NSVM and SVM patients were found to have lower serum levels of HP, Apo A-I, and retinol binding protein 4 (RBP4) (p < 0.05) (Fig. 4A; Table S7). HP and Apo A-I exhibited more than two times lower mean value in SVM patients compared to HC, whereas elevated levels of HP were observed in DF and LEP patients. Serum levels of SAA, Apo-E, HPX, Ceruloplasmin (CP), and Plasminogen (PLS) were found to be significantly higher in both NSVM and SVM patients, compared to HC (Fig. 4A; Table S7). Intriguingly, similar serum levels of Apo E, RBP4 and HPX were observed in DF and LEP patients compared to HC. Serum levels of SOD, VTN and TTN were found to be significantly higher only in SVM patients compared to HC. PLS exhibited slightly higher serum level in SVM compared to NSVM, but the difference in its serum abundance between the severe and non-severe stages was found to be statistically insignificant. Interestingly, SAA, TTN, SOD and CP exhibited differential abundance (>1.5-fold up-regulated) between SVM and NSVM, indicating their potentiality as the predictive markers for malaria severity. In receiver operating characteristic (ROC) curve analysis, SAA, HP, and Apo A-I were found to be efficient (area under the curve (AUC) >0.8) in discrimination of both NSVM and SVM patients from HC (Fig. 4B). However, the efficiency of these candidates was found to be comparatively lower for discrimination of DF or LEP from HC (Fig. S5). Importantly, SOD, VTN, HPX and TTN exhibited adequate prediction accuracy (AUC > 0.70) in discrimination of SVM from NSVM (Fig. 4B; Table S8).


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)

ELISA-based validation of differentially abundant proteins.(A) Determination of serum levels of 11 differentially abundant proteins (identified in the discovery phase of the study) in HC (n = 103), NSVM (n = 118), and SVM (n = 34) by ELISA. **indicates p < 0.001, *indicates 0.001 < p < 0.05 and NS indicates p > 0.05 based on a Mann-Whitney U test. (B) ROC curves depicting accuracy of different serum proteins for prediction of NSVM and SVM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: ELISA-based validation of differentially abundant proteins.(A) Determination of serum levels of 11 differentially abundant proteins (identified in the discovery phase of the study) in HC (n = 103), NSVM (n = 118), and SVM (n = 34) by ELISA. **indicates p < 0.001, *indicates 0.001 < p < 0.05 and NS indicates p > 0.05 based on a Mann-Whitney U test. (B) ROC curves depicting accuracy of different serum proteins for prediction of NSVM and SVM.
Mentions: Compared to HC, both NSVM and SVM patients were found to have lower serum levels of HP, Apo A-I, and retinol binding protein 4 (RBP4) (p < 0.05) (Fig. 4A; Table S7). HP and Apo A-I exhibited more than two times lower mean value in SVM patients compared to HC, whereas elevated levels of HP were observed in DF and LEP patients. Serum levels of SAA, Apo-E, HPX, Ceruloplasmin (CP), and Plasminogen (PLS) were found to be significantly higher in both NSVM and SVM patients, compared to HC (Fig. 4A; Table S7). Intriguingly, similar serum levels of Apo E, RBP4 and HPX were observed in DF and LEP patients compared to HC. Serum levels of SOD, VTN and TTN were found to be significantly higher only in SVM patients compared to HC. PLS exhibited slightly higher serum level in SVM compared to NSVM, but the difference in its serum abundance between the severe and non-severe stages was found to be statistically insignificant. Interestingly, SAA, TTN, SOD and CP exhibited differential abundance (>1.5-fold up-regulated) between SVM and NSVM, indicating their potentiality as the predictive markers for malaria severity. In receiver operating characteristic (ROC) curve analysis, SAA, HP, and Apo A-I were found to be efficient (area under the curve (AUC) >0.8) in discrimination of both NSVM and SVM patients from HC (Fig. 4B). However, the efficiency of these candidates was found to be comparatively lower for discrimination of DF or LEP from HC (Fig. S5). Importantly, SOD, VTN, HPX and TTN exhibited adequate prediction accuracy (AUC > 0.70) in discrimination of SVM from NSVM (Fig. 4B; Table S8).

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