An Echinococcus multilocularis Antigen B3 Proteoform That Shows Specific Antibody Responses to Active-Stage Alveolar Echinococcosis.
Alveolar echinococcosis (AE), caused by the Echinococcus multilocularis metacestode, represents one of the most frequently fatal zoonoses. Early diagnosis significantly reduces morbidity and mortality associated with AE. Diagnosis of AE largely depends on a combination of imaging and serological tests due to its minimal clinical manifestations. Several antigens derived from the whole worm and protoscolex have been targeted for AE serodiagnosis, while the antigenic properties of E. multilocularis hydatid fluid (EmHF) are unclear. We observed two AE-specific 6- and 8-kDa antigen proteoforms through an immunoproteome array of the EmHF. We identified these proteins as representing an E. multilocularis antigen B3 (EmAgB3) isoform, and the proteins were shown to be encoded by the same gene. We cloned the gene and expressed the recombinant EmAgB3 protein (rEmAgB3) in Escherichia coli. rEmAgB3 exhibited sensitivity of 90.9% (80/88 cases) and specificity of 98.5% (597/606 samples) by immunoblotting. The positive and negative predictive values were 89.9% and 98.6%, respectively. The protein did not show antibody responses to 33 AE sera collected during posttreatment follow-up monitoring. Mouse sera experimentally infected with AE protoscoleces began to demonstrate specific antibody responses to native and recombinant EmAgB3 6 months after infection. At that stage, fully mature metacestode vesicles that harbored the brood capsule, primary cell, and protoscolex were observed within an AE mass(es). The response declined along with worm degeneration. Our results demonstrate that the immune responses to this EmAgB3 isoform were highly correlated with worm viability accompanied with AE progression. rEmAgB3 is a promising biomarker for serological assessment of AE patients.
Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, South Korea.
Chun-Seob
CS
Ahn
Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, South Korea Qinghai Province Institute for Endemic Diseases Prevention and Control, Qinghai Centers for Disease Prevention and Control, Xining, China.
Huixia
H
Cai
Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, South Korea.
Jeong-Geun
JG
Kim
Qinghai Province Institute for Endemic Diseases Prevention and Control, Qinghai Centers for Disease Prevention and Control, Xining, China.
Xiumin
X
Han
Qinghai Province Institute for Endemic Diseases Prevention and Control, Qinghai Centers for Disease Prevention and Control, Xining, China.
Xiao
X
Ma
Department of Microbiology, Gachon University Graduate School of Medicine, Incheon, South Korea.
Young-An
YA
Bae
Department of Parasitology, Ewha Womans University, School of Medicine, Seoul, South Korea.
Hyun-Jong
HJ
Yang
Department of Molecular Biology and Biochemistry, School of Medicine, Kyung Hee University, Seoul, South Korea.
Insug
I
Kang
Qinghai Province Institute for Endemic Diseases Prevention and Control, Qinghai Centers for Disease Prevention and Control, Xining, China.
Hu
H
Wang
Department of Molecular Parasitology, Sungkyunkwan University School of Medicine and Center for Molecular Medicine, Samsung Biomedical Research Institute, Suwon, South Korea kongy@skku.edu.
Yoon
Y
Kong
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood*; D000947:Antigens, Helminth / Q000276:immunology*; D002648:Child; D004443:Echinococcosis; D004444:Echinococcosis, Hepatic / Q000175:diagnosis* / Q000276:immunology; D048210:Echinococcus multilocularis / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D012680:Sensitivity and Specificity; D055815:Young Adult
D000909:Antibodies, Helminth; D000947:Antigens, Helminth