Abstract
AbstractSchistosoma 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.