title: 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.
abstract: India significantly contributes to the global malaria burden and has the largest population in the world at risk of malaria. This study aims to analyze alterations in the human serum proteome as a consequence of non-severe and severe infections by the malaria parasite Plasmodium falciparum to identify markers related to disease severity and to obtain mechanistic insights about disease pathogenesis and host immune responses. In discovery phase of the study, a comprehensive quantitative proteomic analysis was performed using gel-based (2D-DIGE) and gel-free (iTRAQ) techniques on two independent mass spectrometry platforms (ESI-Q-TOF and Q-Exactive mass spectrometry), and selected targets were validated by ELISA. Proteins showing altered serum abundance in falciparum malaria patients revealed the modulation of different physiological pathways including chemokine and cytokine signaling, IL-12 signaling and production in macrophages, complement cascades, blood coagulation, and protein ubiquitination pathways. Some muscle related and cytoskeletal proteins such as titin and galectin-3-binding protein were found to be up-regulated in severe malaria patients. Hemoglobin levels and platelet counts were also found to be drastically lower in severe malaria patients. Identified proteins including serum amyloid A, C-reactive protein, apolipoprotein E and haptoglobin, which exhibited sequential alterations in their serum abundance in different severity levels of malaria, could serve as potential predictive markers for disease severity. To the best of our information, we report here the first comprehensive analysis describing the serum proteomic alterations observed in severe P. falciparum infected patients from different malaria endemic regions of India. This article is part of a Special Issue entitled: Proteomics in India.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Sandipan
authors.initials: S
authors.lastname: Ray
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Vipin
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Amruta
authors.initials: A
authors.lastname: Bhave
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Vaidhvi
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel, Mumbai 400012, India.
authors.forename: Nithya J
authors.initials: NJ
authors.lastname: Gogtay
authors.affiliation: Department of Clinical Pharmacology, Seth GS Medical College & KEM Hospital, Parel, Mumbai 400012, India.
authors.forename: Urmila M
authors.initials: UM
authors.lastname: Thatte
authors.affiliation: Department of Medicine, Medical College and Hospital Kolkata, 88, College Street, Kolkata 700073, India.
authors.forename: Arunansu
authors.initials: A
authors.lastname: Talukdar
authors.affiliation: Department of Medicine, Malaria Research Center, S.P. Medical College, Bikaner 334003, India.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Kochar
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Patankar
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. Electronic address: sanjeeva@iitb.ac.in.
authors.forename: Sanjeeva
authors.initials: S
authors.lastname: Srivastava
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000097:blood* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D010963:Plasmodium falciparum; D040901:Proteomics; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: India; Malaria pathogenesis; Plasmodium falciparum; Proteomics; Severe falciparum malaria; Surrogate markers