Immunomics-guided biomarker discovery for human liver fluke infection and infection-associated cholangiocarcinoma

Lakkhana Sadaow, Department of Parasitology, Faculty of Medicine, and Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand.
Rutchanee Rodpai, Department of Parasitology, Faculty of Medicine, and Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand.
Michael J. Smout, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
Rie Nakajima, Vaccine R&D Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, USA.
Patcharaporn Boonroumkaew, Department of Parasitology, Faculty of Medicine, and Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand.
Javier Sotillo, Parasitology Reference and Research Laboratory, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Bemnet A. Tedla, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
Vor Luvira, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Amnat Kitkhuandee, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Krisada Paonariang, Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Wattana Sukeepaisarnjaroen, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Hiroshi Yamasaki, Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan.
Sutas Suttiprapa, Tropical Disease Research Center, Department of Tropical Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Thewarach Laha, Department of Parasitology, Faculty of Medicine, and Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand.
Banchob Sripa, Tropical Disease Research Center, Department of Tropical Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Rafael de Assis, Vaccine R&D Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, USA.
Aarti Jain, Vaccine R&D Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, USA.
Wannaporn Ittiprasert, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Victoria H. Mann, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
Yide Wong, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia.
Philip L. Felgner, Vaccine R&D Center, Department of Physiology and Biophysics, University of California Irvine, Irvine, CA, USA.
Wanchai Maleewong, Department of Parasitology, Faculty of Medicine, and Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand.
Paul J. Brindley, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA. pbrindley@gwu.edu.
Alex Loukas, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia. alex.loukas@jcu.edu.au.
Pewpan M. Intapan, Department of Parasitology, Faculty of Medicine, and Mekong Health Science Research Institute, Khon Kaen University, Khon Kaen, Thailand.

Document Type

Journal Article

Publication Date

7-1-2025

Journal

Nature communications

Volume

16

Issue

1

DOI

10.1038/s41467-025-61043-2

Abstract

Sensitive diagnostics are needed to improve management and surveillance of opisthorchiasis and opisthorchiasis-associated cholangiocarcinoma (CCA) throughout East Asia. Herein we generate and screen an Opisthorchis viverrini recombinant secreted proteome to identity antibody biomarkers of liver fluke infection and CCA with sera from study participants in endemic populations and evaluate their utility as point-of-care immunochromatographic tests (PoC-ICTs). We incorporate two of the most promising antigens from the proteome array screen, P1 and P9, into PoC-ICTs to further validate their diagnostic performance. The P9-IgG4 PoC-ICT is superior amongst the single recombinant antigen tests for diagnosing fluke infection as well as fluke-induced CCA, and out-performs parasite crude extract-IgG ICTs. Here we identify two biomarkers of O. viverrini infection and infection-associated CCA that could form the basis of novel antibody serodiagnostic tests for human liver fluke infection and associated cancer.

Department

Microbiology, Immunology, and Tropical Medicine

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