title: Alteration of immunoproteome profile of Echinococcus granulosus hydatid fluid with progression of cystic echinococcosis.
abstract: BACKGROUND
  Cystic 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  Our 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.
authors.affiliation: Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, 440-746, Korea. feg123@naver.com.
authors.forename: Chun-Seob
authors.initials: CS
authors.lastname: Ahn
authors.affiliation: Qinghai Province Institute for Endemic Diseases Prevention and Control, Xining, Qinghai, China. qhxn_66@163.com.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Microbiology, Graduate School of Medicine, Gachon University, Incheon, Korea. yabae03@gamil.com.
authors.forename: Young-An
authors.initials: YA
authors.lastname: Bae
authors.affiliation: Qinghai Province Institute for Endemic Diseases Prevention and Control, Xining, Qinghai, China. maxiao0971@163.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, 440-746, Korea. bluepine84@nate.com.
authors.forename: Jin-Taek
authors.initials: JT
authors.lastname: Kim
authors.affiliation: Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, 440-746, Korea. huixia_1107@163.com.|Qinghai Province Institute for Endemic Diseases Prevention and Control, Xining, Qinghai, China. huixia_1107@163.com.
authors.forename: Huixia
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Parasitology, Ewha Womans University, School of Medicine, Seoul, Korea. parayang@ewha.ac.kr.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Yang
authors.affiliation: Department of Molecular Biology and Biochemistry, School of Medicine, Kyung Hee University, Seoul, Korea. iskang@kku.ac.kr.
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.affiliation: Qinghai Province Institute for Endemic Diseases Prevention and Control, Xining, Qinghai, China. whqhxn@126.com.
authors.forename: Hu
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, 440-746, Korea. kongy@skku.edu.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Kong
mesh_terms: D000818:Animals; D020420:Cyst Fluid / Q000737:chemistry*; D004443:Echinococcosis / Q000469:parasitology*; D048209:Echinococcus granulosus / Q000378:metabolism*; D005260:Female; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007162:Immunoproteins / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D020033:Protein Isoforms; D040901:Proteomics; D059467:Transcriptome
chemical_list: D015801:Helminth Proteins; D007162:Immunoproteins; D020033:Protein Isoforms