BackgroundSchistosomiasis is an important helminth infection of humans. There are few reliable diagnostic biomarkers for early infection, for recurrent infection or to document successful treatment. In this study, we compared serum protein profiles in uninfected and infected mice to identify disease stage-specific biomarkers.MethodsSerum collected from CD1 mice infected with 50–200 Schistosoma mansoni cercariae were analyzed before infection and at 3, 6 and 12 weeks post-infection using three mass spectrometric (MS) platforms.ResultsUsing SELDI-TOF MS, 66 discriminating m/z peaks were detected between S. mansoni infected mice and healthy controls. Used in various combinations, these peaks could 1) reliably diagnose early-stage disease, 2) distinguish between acute and chronic infection and 3) diagnose S. mansoni infection regardless the parasite burden. The most important contributors to these diagnostic algorithms were peaks at 3.7, 13 and 46 kDa. Employing sample fractionation and differential gel electrophoresis, we analyzed gel slices either by MALDI-TOF MS or Velos Orbitrap MS. The former yielded eight differentially-expressed host proteins in the serum at different disease stages including transferrin and alpha 1- antitrypsin. The latter suggested the presence of a surprising number of parasite-origin proteins in the serum during both the acute (n = 200) and chronic (n = 105) stages. The Orbitrap platform also identified many differentially-expressed host-origin serum proteins during the acute and chronic stages (296 and 220 respectively). The presence of one of the schistosome proteins, glutathione S transferase (GST: 25 KDa), was confirmed by Western Blot. This study provides proof-of-principle for an approach that can yield a large number of novel candidate biomarkers for Schistosoma infection.

Abstract. Schistosoma mansoni 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 S. mansoni-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 P < 0.001) and ELISA (human: P < 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 S. mansoni infection.

Abstract. CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/347278 doi: bioRxiv preprint first posted online Jun. 14, 2018; 26Schistosomiasis is one of the most socioeconomically exhausting parasitic 27 infection in tropical and subtropical areas. Praziquantel (PZQ), the only common 28 schistosocidal drug in use, is not efficient enough for treatment of immature infection. 29Arabic gum (AG) is a complex polysaccharide acts as anti-oxidant which modulates the Author summary 46Schistosomiasis is a major public health threat in many parts of the world, it 47 affects more than 240 million people in more than 70 countries and almost 800 million 48 people are at risk of acquiring this disease. Serious consequences and disabilities might . CC-BY 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/347278 doi: bioRxiv preprint first posted online Jun. 14, 2018;