title: Identification of circulating biomarkers in sera of Plasmodium knowlesi-infected malaria patients--comparison against Plasmodium vivax infection.
abstract: BACKGROUND
  Plasmodium knowlesi was identified as the fifth major malaria parasite in humans. It presents severe clinical symptoms and leads to mortality as a result of hyperparasitemia in a short period of time. This study aimed to improve the current understanding of P. knowlesi and identify potential biomarkers for knowlesi malaria.
  
  
  METHODS
  In the present study, we have employed two-dimensional gel electrophoresis-coupled immunoblotting techniques and mass spectrometry to identify novel circulating markers in sera from P. knowlesi-infected patients. Specifically, we have compared serum protein profiles from P. knowlesi-infected patients against those of healthy or P. vivax-infected individuals.
  
  
  RESULTS
  We identified several immunoreactive proteins in malarial-infected subjects, including alpha-2-HS glycoprotein (AHSG), serotransferrin (TF), complement C3c (C3), hemopexin (HPX), zinc-2-alpha glycoprotein (ZAG1), apolipoprotein A1 (Apo-A1), haptoglobin (HAP), and alpha-1-B-glycoprotein (A1BG). However, only TF and HPX displayed enhanced antigenicity and specificity, suggesting that they might represent valid markers for detecting P. knowlesi infection. Additionally, six P. knowlesi-specific antigens were identified (K15, K16, K28, K29, K30, and K38). Moreover, although HAP antigenicity was observed during P. vivax infection, it was undetectable in P. knowlesi-infected subjects.
  
  
  CONCLUSIONS
  We have demonstrated the application of immunoproteomics approach to identify potential candidate biomarkers for knowlesi malaria infection.
authors: Department of Oral Biology & Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia. chenyeng@um.edu.my.|Oral Cancer Research and Coordinating Center, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. chenyeng@um.edu.my.
authors: Yeng
authors: Y
authors: Chen
authors: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Gelugor, Penang, Malaysia. stevenkeat@gmail.com.
authors: Choon K
authors: CK
authors: Chan
authors: Department of Oral Biology & Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia. jesindapaul@yahoo.co.uk.
authors: Jesinda P
authors: JP
authors: Kerishnan
authors: Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. lauyeeling@um.edu.my.
authors: Yee L
authors: YL
authors: Lau
authors: Department of Oral Biology & Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia. wyl_1230@yahoo.com.
authors: Yin-Ling
authors: YL
authors: Wong
authors: Department of Oral Biology & Biomedical Sciences, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia. subash@unimap.edu.my.|Institute of Nano Electronic Engineering (INEE), & School of Bioprocess Engineering, Universiti Malaysia Perlis, Kangar, Perlis, Malaysia. subash@unimap.edu.my.
authors: Subash Cb
authors: SC
authors: Gopinath
mesh_terms: D000328:Adult; D000953:Antigens, Protozoan / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008288:Malaria / Q000097:blood / Q000175:diagnosis* / Q000469:parasitology; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D016790:Plasmodium knowlesi / Q000276:immunology / Q000472:pathogenicity*; D010966:Plasmodium vivax / Q000276:immunology / Q000472:pathogenicity*; D012680:Sensitivity and Specificity
chemical_list: D000953:Antigens, Protozoan; D015415:Biomarkers
references: Nature. 1986 Nov 27-Dec 3;324(6095):388-91
references: 3097554
references: PLoS Pathog. 2005 Dec;1(4):e44
references: 16389297
references: Biol Met. 1989;2(3):174-84
references: 2535180
references: Clin Chim Acta. 2001 Oct;312(1-2):13-23
references: 11580905
references: Anal Chem. 1996 Mar 1;68(5):850-8
references: 8779443
references: Blood. 1986 May;67(5):1519-21
references: 3516259
references: Microbes Infect. 2002 May;4(6):581-90
references: 12048027
references: Nucleic Acids Res. 2009 Jan;37(1):1-13
references: 19033363
references: Clin Infect Dis. 2008 Jan 15;46(2):165-71
references: 18171245
references: Nature. 2005 Sep 8;437(7056):E3-4; discussion E4-5
references: 16148887
references: Int J Parasitol. 2002 Sep;32(10):1225-34
references: 12204222
references: Exp Parasitol. 1985 Oct;60(2):171-4
references: 4029347
references: Electrophoresis. 2010 Dec;31(23-24):3843-9
references: 21080484
references: Microbes Infect. 2012 Mar;14(3):207-16
references: 22033148
references: Am J Trop Med Hyg. 2006 Jun;74(6):965-71
references: 16760505
references: Trends Parasitol. 2008 Dec;24(12):545-50
references: 18938107
references: PLoS One. 2009;4(3):e4912
references: 19300530
references: Malar J. 2011;10:197
references: 21774805
references: J Cell Biol. 1975 Apr;65(1):51-64
references: 1127015
references: Electrophoresis. 1988 Jan;9(1):28-32
references: 2466645
references: Emerg Infect Dis. 2008 Nov;14(11):1750-2
references: 18976561
references: BMJ. 2007 Feb 24;334(7590):403
references: 17259188
references: Clin Infect Dis. 2008 Jan 15;46(2):172-3
references: 18171246
references: J Mol Med (Berl). 2008 Oct;86(10):1097-111
references: 18641963
references: Lancet. 2004 Mar 27;363(9414):1017-24
references: 15051281
references: Infect Immun. 2005 Sep;73(9):6091-100
references: 16113330
references: J Immunol. 2012 Dec 1;189(11):5336-46
references: 23100518
references: Infect Immun. 1992 Sep;60(9):3872-7
references: 1500194
references: Front Pharmacol. 2014 May 06;5:84
references: 24834053
references: Nature. 2008 Oct 9;455(7214):799-803
references: 18843368
references: Microbes Infect. 2001 Jul;3(9):689-99
references: 11489417
references: Malar J. 2009;8:73
references: 19383118
references: PLoS One. 2012;7(8):e41751
references: 22912677
references: Nucleic Acids Res. 2013 Jan;41(Database issue):D808-15
references: 23203871
references: Nat Protoc. 2009;4(1):44-57
references: 19131956
references: Parasite Immunol. 2005 May;27(5):171-80
references: 15987340
references: Proteome Sci. 2008 Jul 18;6:20
references: 18637207
references: Clin Microbiol Rev. 2013 Apr;26(2):165-84
references: 23554413
references: Clin Infect Dis. 2009 Sep 15;49(6):852-60
references: 19635025
references: Infect Immun. 1997 Nov;65(11):4696-700
references: 9353052
references: Infect Immun. 1998 Sep;66(9):4511-6
references: 9712810
references: Redox Rep. 2001;6(6):389-92
references: 11865983
references: Emerg Infect Dis. 2004 Dec;10(12):2211-3
references: 15663864