Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity

S, Ray; Kumar, Vipin; Bhave, A.G.; Singh, Vaidhvi; Gogtay, Nithya J; Thatte, Urmila M; Talukdar, Arunansu; Kochar, Sanjay Kumar; Patankar, Swati; Srivastava, Sanjeeva

doi:10.1016/j.jprot.2015.04.032

Cited by 18 publications

(26 citation statements)

References 47 publications

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“…In recent years, plasma/serum proteomics studies have contributed substantially to elucidate the complex pathogenesis of malaria and other infectious diseases 17,18 . Intriguingly, several studies from our and other research groups have defined promising panels of plasma and serum markers in falciparum [19][20][21][22][23][24] and vivax 19,25,26 malaria. A considerable amount of further research is required to understand the complex pathophysiology of severe malaria [27][28][29] .…”

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confidence: 99%

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity

Kumar

Aggarwal

et al. 2020

Commun Biol

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Management of severe malaria remains a critical global challenge. In this study, using a multiplexed quantitative proteomics pipeline we systematically investigated the plasma proteome alterations in non-severe and severe malaria patients. We identified a few parasite proteins in severe malaria patients, which could be promising from a diagnostic perspective. Further, from host proteome analysis we observed substantial modulations in many crucial physiological pathways, including lipid metabolism, cytokine signaling, complement, and coagulation cascades in severe malaria. We propose that severe manifestations of malaria are possibly underpinned by modulations of the host physiology and defense machinery, which is evidently reflected in the plasma proteome alterations. Importantly, we identified multiple blood markers that can effectively define different complications of severe falciparum malaria, including cerebral syndromes and severe anemia. The ability of our identified blood markers to distinguish different severe complications of malaria may aid in developing new clinical tests for monitoring malaria severity.

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confidence: 99%

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity

Kumar

Aggarwal

et al. 2020

Commun Biol

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“…Previous studies using proteomics techniques, Western blots, and ELISA have shown that haptoglobin is highly downregulated in severe malaria as compared to non‐severe and community controls . Here, we have performed the highly quantitative MRM assay to validate the results of haptoglobin and show the downregulation of this acute‐phase protein in malaria patients.…”

Section: Discussionmentioning

confidence: 81%

“…Previous proteomics studies from our lab showed that levels of haptoglobin were highly dysregulated in severe malaria cases as compared to non‐severe malaria. Hence, haptoglobin was used for the MRM studies, and three unique peptides were screened.…”

Section: Methodsmentioning

confidence: 81%

A Proteogenomic Analysis of Haptoglobin in Malaria

Awasthi

Tyagi

Kumar

et al. 2017

Proteomics Clinical Apps

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“…Our data shows that the degree of intravascular hemolysis in the SMA group is not different to that of other malaria positive groups. In acute-onset life-threatening childhood SMA rapid PCV decrease 58 is predominantly driven by increased clearance of uninfected erythrocytes by the reticulo-endothelial system 49 as intravascular hemolysis of infected erythrocytes due to schizogony cannot explain by itself this dramatic change. In line with our previous SMA study 49 , we suggest that, in the cohorts with baseline low plasma HP and Hb, particularly the SMA group, clearance of non-infected erythrocytes is driven by the reticulo-endothelial system in the spleen through an as yet unknown CD8(+) T-cell-dependent mechanism 49 .…”

Section: Discussionmentioning

confidence: 99%

Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis

Abah

Burté

Marquet

et al. 2018

Sci Rep

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Severe Malarial Anemia (SMA), a life-threatening childhood Plasmodium falciparum malaria syndrome requiring urgent blood transfusion, exhibits inflammatory and hemolytic pathology. Differentiating between hypo-haptoglobinemia due to hemolysis or that of genetic origin is key to understand SMA pathogenesis. We hypothesized that while malaria-induced hypo-haptoglobinemia should reverse at recovery, that of genetic etiology should not. We carried-out a case-control study of children living under hyper-endemic holoendemic malaria burden in the sub-Saharan metropolis of Ibadan, Nigeria. We show that hypo-haptoglobinemia is a risk factor for childhood SMA and not solely due to intravascular hemolysis from underlying schizogony. In children presenting with SMA, hypo-haptoglobinemia remains through convalescence to recovery suggesting a genetic cause. We identified a haptoglobin gene variant, rs12162087 (g.-1203G > A, frequency = 0.67), to be associated with plasma haptoglobin levels (p = 8.5 × 10−6). The Homo-Var:(AA) is associated with high plasma haptoglobin while the reference Homo-Ref:(GG) is associated with hypo-haptoglobinemia (p = 2.3 × 10−6). The variant is associated with SMA, with the most support for a risk effect for Homo-Ref genotype. Our insights on regulatory haptoglobin genotypes and hypo-haptoglobinemia suggest that haptoglobin screening could be part of risk-assessment algorithms to prevent rapid disease progression towards SMA in regions with no-access to urgent blood transfusion where SMA accounts for high childhood mortality rates.

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Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity

Cited by 18 publications

References 47 publications

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity

Multiplexed quantitative proteomics provides mechanistic cues for malaria severity and complexity

A Proteogenomic Analysis of Haptoglobin in Malaria

Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis

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