1921
Volume 96, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

is a major public health threat in many parts of the world. The current diagnostic tests for schistosomiasis are suboptimal, particularly early in infection, when the parasite burden is low and with reinfection after treatment. We sought to identify novel biomarkers of active infection by studying serum proteins in a mouse model of schistosomiasis followed by confirmation in chronically infected patients. Acute (6 weeks) and chronic (12 weeks) sera from –infected C57Bl/6 mice as well as sera from chronically infected patients were assessed using two proteomic platforms: surface-enhanced, laser desorption and ionization, time-of-flight mass spectrometry and Velos Orbitrap mass spectrometry. Several candidate biomarkers were further evaluated by Western blot and/or enzyme-linked immunosorbent assay (ELISA). Among the most promising was carbonic anhydrase 1 (CA1), a host protein found primarily in red blood cells and enterocytes that proved to be a negative biomarker for schistosomiasis in both mouse and human samples. Reduced serum CA-1 levels were confirmed by both Western blot (murine and human: both < 0.001) and ELISA (human: < 0.01). Western blots of serial mouse sera revealed a progressive reduction in serum CA1 levels over the 12-week infection period. CA1 is a promising negative serum biomarker for the diagnosis of infection.

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2017-04-05
2018-07-17
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References

  1. Elhag SM, Abdelkareem EA, Yousif AS, Frah EA, Mohamed AB, , 2011. Detection of schistosomiasis antibodies in urine patients as a promising diagnostic maker. Asian Pac J Trop Med 4: 773777.[Crossref]
  2. Kinkel HF, Dittrich S, Bäumer B, Weitzel T, , 2012. Evaluation of eight serological tests for diagnosis of imported schistosomiasis. Clin Vaccine Immunol 19: 948953.[Crossref]
  3. Hipgrave DB, Leydon JA, Walker J, Biggs BA, , 1997. Schistosomiasis in Australian travellers to Africa. Med J Aust 166: 294297.
  4. Visser LG, Polderman AM, Stuiver PC, , 1995. Outbreak of schistosomiasis among travelers returning from Mali, west Africa. Clin Infect Dis 20: 280285.[Crossref]
  5. Whitty CJ, Mabey DC, Armstrong M, Wright SG, Chiodini PL, , 2000. Presentation and outcome of 1107 cases of schistosomiasis from Africa diagnosed in a non-endemic country. Trans R Soc Trop Med Hyg 94: 531534.[Crossref]
  6. Golledge CL, , 1995. Schistosomiasis: beware delayed seroconversion. Med J Aust 163: 446447.
  7. Jones ME, Mitchell RG, Leen CL, , 1992. Long seronegative window in Schistosoma infection. Lancet 340: 15491550.[Crossref]
  8. Jordan P, Webbe G, , 1969. Human Schistosomiasis. London, United Kingdom: Heinemann.
  9. Doenhoff MJ, Chiodini PL, Hamilton JV, , 2004. Specific and sensitive diagnosis of schistosome infection: can it be done with antibodies? Trends Parasitol 20: 3539.[Crossref]
  10. Bica I, Hamer DH, Stadecker MJ, , 2000. Hepatic schistosomiasis. Infect Dis Clin North Am 14: 583604.[Crossref]
  11. Farah IO, Kariuki TM, King CL, Hau J, , 2001. An overview of animal models in experimental schistosomiasis and refinements in the use of non-human primates. Lab Anim 35: 205212.[Crossref]
  12. Pearce EJ, MacDonald AS, , 2002. The immunobiology of schistosomiasis. Nat Rev Immunol 2: 499511.[Crossref]
  13. El Ridi R, Wagih A, Salem R, Mahana N, El Demellawy M, Tallima H, , 2006. Impact of interleukin-1 and interleukin-6 in murine primary schistosomiasis. Int Immunopharmacol 6: 11001108.[Crossref]
  14. Byram JE, von Lichtenberg F, , 1977. Altered schistosome granuloma formation in nude mice. Am J Trop Med Hyg 26: 944956.
  15. Byram JE, Doenhoff MJ, Musallam R, Brink LH, Von Lichtenberg F, , 1979. Schistosoma mansoni infections in T-cell deprived mice, and the ameliorating effect of administering homologous chronic infection serum. II. Pathology. Am J Trop Med Hyg 28: 274285.
  16. Amiri P, Locksley RM, Parslow TG, Sadickt M, Rector E, Ritter D, McKerrow JH, , 1992. Tumor necrosis alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice. Nature 356: 604607.[Crossref]
  17. Lewis FA, Stirewalt MA, Souza CP, Gazzinelli G, , 1986. Large-scale laboratory maintenance of Schistosoma mansoni, with observations on three schistosome/snail host combinations. J Parasitol 72: 813829.[Crossref]
  18. Ndao M, Spithill TW, Caffrey R, Li H, Podust VN, Perichon R, Santamaria C, Ache A, Duncan M, Powell MR, Ward BJ, , 2010. Identification of novel diagnostic serum biomarkers for Chagas' disease in asymptomatic subjects by mass spectrometric profiling. J Clin Microbiol 48: 11391149.[Crossref]
  19. Chrambach A, Reisfeld RA, Wyckoff M, Zaccari J, , 1967. A procedure for rapid and sensitive staining of protein fractionated by polyacrylamide gel electrophoresis. Anal Biochem 20: 150154.[Crossref]
  20. Piersma SR, Warmoes MO, de Wit M, de Reus I, Knol JC, Jiménez CR, , 2013. Whole gel processing procedure for GeLC-MS/MS based proteomics. Proteome Sci 11: 17.[Crossref]
  21. Schenk S, Schoenhals GJ, de Souza G, Mann M, , 2008. A high confidence, manually validated human blood plasma protein reference set. BMC Med Genomics 1: 41.[Crossref]
  22. Olsen JV, de Godoy LM, Li G, Macek B, Mortensen P, Pesch R, Makarov A, Lange O, Horning S, Mann M, , 2005. Parts per million mass accuracy on an Orbitrap mass spectrometer via a lock mass injection into a C-trap. Mol Cell Proteomics 4: 20102021.[Crossref]
  23. Keller A, Nesvizhskii AI, Kolker E, Aebersold R, , 2002. Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search. Anal Chem 74: 53835392.[Crossref]
  24. Nesvizhskii AI, Keller A, Kolker E, Aebersold R, , 2003. A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 75: 46464658.[Crossref]
  25. Welinder C, Ekblad L, , 2012. Coomassie staining as loading control in Western blot analysis. J Proteome Res 10: 14161419.[Crossref]
  26. Aldridge GM, Podrebarac DM, Greenough WT, Weiler IJ, , 2008. The use of total protein stains as loading controls: an alternative to high-abundance single-protein controls in semi-quantitative immunoblotting. J Neurosci Methods 172: 250254.[Crossref]
  27. Moreels TG, Joris G, Bogers JJ, De Winter BY, Vrolix G, Herman AG, Van Marck EA, Pelckmans PA, , 2001. Effect of Schistosoma mansoni-induced granulomatous inflammation on murine gastrointestinal motility. Am J Physiol Gastrointest Liver Physiol 280: G1030G1042.
  28. Bondarenko PV, Chelius D, Shaler TA, , 2002. Identification and relative quantitation of protein mixtures by enzymatic digestion followed by capillary reversed-phase liquid chromatography-tandem mass spectrometry. Anal Chem 74: 47414749.[Crossref]
  29. Lu P, Vogel C, Wang R, Yao X, Marcotte EM, , 2007. Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Nat Biotechnol 25: 117124.[Crossref]
  30. Wang M, You J, Bemis KG, Tegeler TJ, Brown DP, , 2008. Label-free mass spectrometry-based protein quantification technologies in proteomic analysis. Brief Funct Genomics Proteomics 7: 329339.[Crossref]
  31. Fournier PE, Drancourt M, Colson P, Rolain JM, La Scola B, Raoult D, , 2013. Modern clinical microbiology: new challenges and solutions. Nat Rev Microbiol 11: 574585.[Crossref]
  32. Seibert V, Wiesner A, Buschmann T, Meuer J, , 2004. Surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI TOF-MS) and ProteinChip® technology in proteomics research. Pathol Res Pract 200: 8394.[Crossref]
  33. Swenson ER, Dogson SJ, Tashian R, Gros G, Carter ND, , 1991. Distribution and functions of anhydrase in the gastrointestinal tract. , eds. The Carbonic Anhydrases. New York, NY: Springer, 265287.[Crossref]
  34. Supuran CT, , 2010. Carbonic anhydrase inhibition/activation: trip of a scientist around the world in the search of novel chemotypes and drug targets. Curr Pharm Des 16: 32333245.[Crossref]
  35. Ferry JG, , 2010. The γ class of carbonic anhydrases. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics 1804: 374381.[Crossref]
  36. Lane TW, Morel FM, , 2000. A biological function for cadmium in marine diatoms. Proc Natl Acad Sci USA 97: 46274631.[Crossref]
  37. Lane TW, Saito MA, George GN, Pickering IJ, Prince RC, Morel FM, , 2005. Biochemistry: a cadmium enzyme from a marine diatom. Nature 435: 42.[Crossref]
  38. Elleuche S, Poggeler S, , 2010. Carbonic anhydrases in fungi. Microbiology 156: 2329.[Crossref]
  39. Elleuche S, Poggeler S, , 2009. Evolution of carbonic anhydrases in fungi. Curr Genet 55: 211222.[Crossref]
  40. Güzel O, Maresca A, Scozzafava A, Salman A, Balaban AT, Supuran CT, , 2009. Discovery of low nanomolar and subnanomolar inhibitors of the mycobacterial β-carbonic anhydrases Rv1284 and Rv3273. J Med Chem 52: 40634067.[Crossref]
  41. Konialis CP, Barlow JH, Butterworth PH, , 1985. Cloned cDNA for rabbit erythrocyte carbonic anhydrase I: a novel erythrocyte-specific probe to study development in erythroid tissues. Proc Natl Acad Sci USA 82: 663667.[Crossref]
  42. Parkkila S, Parkkila AK, Juvonen T, Rajaniemi H, , 1994. Distribution of the carbonic anhydrase isoenzymes I, II, and VI in the human alimentary tract. Gut 35: 646650.[Crossref]
  43. Campbell AR, Andress OL, Swenson ER, , 1994. Identification and characterization of human neutrophil carbonic anhydrase. J Leukoc Biol 55: 343348.
  44. Kuo WH, Yang SF, Hsieh YS, Tsai CS, Hwang WL, Chu SC, , 2005. Differential expression of carbonic anhydrase isoenzymes in various types of anemia. Clin Chim Acta 351: 7986.[Crossref]
  45. Giovanni RF, Renzo L, Giuseppe C, Adriana F, Sambuy MY, , 1998. Carbonic anhydrase I reduction in colonic mucosa of patients with active ulcerative colitis. Dig Dis Sci 43: 20862092.[Crossref]
  46. Robinson CE, Kottapalli V, D'astice M, Fields JZ, Winship D, Keshavarzian A, , 1997. Regulation of neutrophils in ulcerative colitis by colonic factors: a possible mechanism of neutrophil activation and tissue damage. J Lab Clin Med 130: 590602.[Crossref]
  47. Mohamed AR, Al Karawi M, Yasawy MI, , 1990. Schistosomal colonic disease. Gut 31: 439442.[Crossref]
  48. El Hawy AM, Abdel RM, Rozik S, Fawzy AF, el Gammal HA, , 1993. Assessment of serum copper and zinc levels in chronic Schistosoma mansoni patients with and without hepatic involvement before and after praziquantel therapy. J Egypt Soc Parasitol 23: 5562.
  49. Tripp BC, Smith K, Ferry JG, , 2001. Carbonic anhydrase: new insights for an ancient enzyme. J Biol Chem 276: 4861548618.[Crossref]
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  • Received : 07 Jan 2016
  • Accepted : 31 Oct 2016

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