Abstract
BackgroundCystic echinococcosis (CE), caused by Echinococcus granulosus metacestode, invokes a serious public health concern. Early diagnosis has great impacts on reduction of disability-adjusted life years. Several antigen B-related molecules (EgAgB; EgAgB1-5) are known to be immunopotent, but detection of EgAgB is variable in many patients and may not allow reliable interpretation of its immunological relevance. More importantly, the immunoproteome profile of hydatid fluid (HF) has not been addressed.MethodsWe conducted a proteome analysis of the HF of a single fertile cyst of CE1 and CE2 stages through two-dimensional electrophoresis (2-DE). Each protein spot was analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We subsequently determined the immunoproteome profile employing patient sera of entire disease spectrum from CE1 to CE5 stages.ResultsWe identified 40 parasite proteins, of which EgAgB (28 spots) and antigen 5 (EgAg5; 5 molecules) were abundant. EgAgB proteoforms constituted the majority, mostly EgAgB1 (24 spots), followed by EgAgB2 and EgAgB4 (2 spots each). EgAgB3 was detected only by liquid chromatography-MS/MS. EgAgB5 was not recognized. We also detected 38 host proteins, which were largely composed of serum components, antioxidant/xenobiotic enzymes, and enzymes involved in carbohydrate metabolism. CE1 and CE2 HF exhibited comparable spotting patterns, but CE2 HF harbored greater amounts of EgAgB and EgAg5 complexes. CE sera demonstrated complicated immune recognition patterns according to the disease progression; CE2 and CE3 stages exhibited strong antibody responses against diverse EgAgB and EgAg5 proteoforms, while CE1, CE4, and CE5 stages mainly reacted to EgAg5 and cathepsin B. Patient sera of alveolar echinococcosis (AE) cross-reacted with diverse EgAgB isoforms (36%). EgAg5 and cathepsin B also demonstrated cross-reactions with sera from neurocysticercosis and sparganosis.ConclusionsOur results demonstrated that detection of a single defined molecule may not properly diagnose CE, since specific immunodominant epitopes changed as the disease progresses. Immunoproteome analysis combined with imaging studies may be practical in the differential diagnosis of CE from AE and other cystic lesions, as well as for staging CE, which are pertinent to establish appropriate patient management.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-014-0610-7) contains supplementary material, which is available to authorized users.
Highlights
Cystic echinococcosis (CE), caused by Echinococcus granulosus metacestode, invokes a serious public health concern
Proteomic analysis of E. granulosus hydatid fluid (HF) collected from different CE stages reveals similar spotting patterns, but CE2 HF harbored enriched Echinococcus granulosus antigen B (EgAgB) and EgAg5 proteoforms In order to comparatively delineate HF proteins of different CE stages, we determined the protein profile of a single fertile CE1 and CE2 cyst
Serological cross-reactions between CE and alveolar echinococcosis (AE) may be inherent to some extent due to the highly conserved sequence identity between EgAgBs and EmAgBs (78.8-94.2%), except for the antigen B3 series (36.5%), which did not invoke a significant antibody response against CE patients
Summary
Cystic echinococcosis (CE), caused by Echinococcus granulosus metacestode, invokes a serious public health concern. Several antigen B-related molecules (EgAgB; EgAgB1-5) are known to be immunopotent, but detection of EgAgB is variable in many patients and may not allow reliable interpretation of its immunological relevance. Cystic echinococcosis (CE), caused by Echinococcus granulosus metacestode, is one of the most deleterious helminthic diseases of humans and livestock. Oncospheres hatched from the eggs are activated in the small intestine and subsequently penetrate the intestinal wall to enter the circulation. They mostly egress in the liver and lung, and grow slowly to hydatid fluid (HF)-filled cyst, in which many protoscoleces and daughter cysts develop [5]
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