Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study

Summary: Background: Sensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infectio...

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Autores principales:	Mark S Pearson, PhD, Bemnet A Tedla, PhD, Gebeyaw G Mekonnen, PhD, Carla Proietti, PhD, Luke Becker, BSc, Rie Nakajima, MSc, Al Jasinskas, PhD, Denise L Doolan, PhD, Abena S Amoah, PhD, Stefanie Knopp, PhD, David Rollinson, PhD, Said M Ali, MSc, Fatma Kabole, MD, Cornelis H Hokke, PhD, Akim A Adegnika, MD, Matt A Field, PhD, Govert van Dam, PhD, Paul L A M Corstjens, PhD, Takafira Mduluza, PhD, Francisca Mutapi, PhD, Claude Oeuvray, PhD, Beatrice Greco, PhD, Sujittra Chaiyadet, PhD, Thewarach Laha, PhD, Pengfei Cai, PhD, Donald P McManus, PhD, Maria Elena Bottazzi, PhD, Philip L Felgner, PhD, Javier Sotillo, PhD, Alex Loukas, PhD
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Medicine (General) R5-920 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e9c0510583ca4bf58360b82613221a36
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spelling	oai:doaj.org-article:e9c0510583ca4bf58360b82613221a362021-11-04T04:40:55ZImmunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study2666-524710.1016/S2666-5247(21)00150-6https://doaj.org/article/e9c0510583ca4bf58360b82613221a362021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666524721001506https://doaj.org/toc/2666-5247Summary: Background: Sensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infection, validate their diagnostic performance in samples from endemic populations, and evaluate their utility as point of care immunochromatographic tests (POC-ICTs) to diagnose urogenital schistosomiasis in the field. Methods: We did a biomarker identification study, in which we constructed a proteome array containing 992 validated and predicted proteins from S haematobium and screened it with serum and urine antibodies from endemic populations in Gabon, Tanzania, and Zimbabwe. Arrayed antigens that were IgG-reactive and a select group of antigens from the worm extracellular vesicle proteome, predicted to be diagnostically informative, were then evaluated by ELISA using the same samples used to probe arrays, and samples from individuals residing in a low-endemicity setting (ie, Pemba and Unguja islands, Zanzibar, Tanzania). The two most sensitive and specific antigens were incorporated into POC-ICTs to assess their ability to diagnose S haematobium infection from serum in a field-deployable format. Findings: From array probing, in individuals who were infected, 208 antigens were the targets of significantly elevated IgG responses in serum and 45 antigens were the targets of significantly elevated IgG responses in urine. Of the five proteins that were validated by ELISA, Sh-TSP-2 (area under the curve [AUC]serum=0·98 [95% CI 0·95–1·00]; AUCurine=0·96 [0·93–0·99]), and MS3_01370 (AUCserum=0·93 [0·89–0·97]; AUCurine=0·81 [0·72–0·89]) displayed the highest overall diagnostic performance in each biofluid and exceeded that of S haematobium-soluble egg antigen in urine (AUC=0·79 [0·69–0·90]). When incorporated into separate POC-ICTs, Sh-TSP-2 showed absolute specificity and a sensitivity of 75% and MS3_01370 showed absolute specificity and a sensitivity of 89%. Interpretation: We identified numerous biomarkers of urogenital schistosomiasis that could form the basis of novel antibody diagnostics for this disease. Two of these antigens, Sh-TSP-2 and MS3_01370, could be used as sensitive, specific, and field-deployable diagnostics to support schistosomiasis control and elimination initiatives, with particular focus on post-elimination surveillance. Funding: Australian Trade and Investment Commission and Merck Global Health Institute.Mark S Pearson, PhDBemnet A Tedla, PhDGebeyaw G Mekonnen, PhDCarla Proietti, PhDLuke Becker, BScRie Nakajima, MScAl Jasinskas, PhDDenise L Doolan, PhDAbena S Amoah, PhDStefanie Knopp, PhDDavid Rollinson, PhDSaid M Ali, MScFatma Kabole, MDCornelis H Hokke, PhDAkim A Adegnika, MDMatt A Field, PhDGovert van Dam, PhDPaul L A M Corstjens, PhDTakafira Mduluza, PhDFrancisca Mutapi, PhDClaude Oeuvray, PhDBeatrice Greco, PhDSujittra Chaiyadet, PhDThewarach Laha, PhDPengfei Cai, PhDDonald P McManus, PhDMaria Elena Bottazzi, PhDPhilip L Felgner, PhDJavier Sotillo, PhDAlex Loukas, PhDElsevierarticleMedicine (General)R5-920MicrobiologyQR1-502ENThe Lancet Microbe, Vol 2, Iss 11, Pp e617-e626 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920 Microbiology QR1-502
spellingShingle	Medicine (General) R5-920 Microbiology QR1-502 Mark S Pearson, PhD Bemnet A Tedla, PhD Gebeyaw G Mekonnen, PhD Carla Proietti, PhD Luke Becker, BSc Rie Nakajima, MSc Al Jasinskas, PhD Denise L Doolan, PhD Abena S Amoah, PhD Stefanie Knopp, PhD David Rollinson, PhD Said M Ali, MSc Fatma Kabole, MD Cornelis H Hokke, PhD Akim A Adegnika, MD Matt A Field, PhD Govert van Dam, PhD Paul L A M Corstjens, PhD Takafira Mduluza, PhD Francisca Mutapi, PhD Claude Oeuvray, PhD Beatrice Greco, PhD Sujittra Chaiyadet, PhD Thewarach Laha, PhD Pengfei Cai, PhD Donald P McManus, PhD Maria Elena Bottazzi, PhD Philip L Felgner, PhD Javier Sotillo, PhD Alex Loukas, PhD Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study
description	Summary: Background: Sensitive diagnostics are needed for effective management and surveillance of schistosomiasis so that current transmission interruption goals set by WHO can be achieved. We aimed to screen the Schistosoma haematobium secretome to find antibody biomarkers of schistosome infection, validate their diagnostic performance in samples from endemic populations, and evaluate their utility as point of care immunochromatographic tests (POC-ICTs) to diagnose urogenital schistosomiasis in the field. Methods: We did a biomarker identification study, in which we constructed a proteome array containing 992 validated and predicted proteins from S haematobium and screened it with serum and urine antibodies from endemic populations in Gabon, Tanzania, and Zimbabwe. Arrayed antigens that were IgG-reactive and a select group of antigens from the worm extracellular vesicle proteome, predicted to be diagnostically informative, were then evaluated by ELISA using the same samples used to probe arrays, and samples from individuals residing in a low-endemicity setting (ie, Pemba and Unguja islands, Zanzibar, Tanzania). The two most sensitive and specific antigens were incorporated into POC-ICTs to assess their ability to diagnose S haematobium infection from serum in a field-deployable format. Findings: From array probing, in individuals who were infected, 208 antigens were the targets of significantly elevated IgG responses in serum and 45 antigens were the targets of significantly elevated IgG responses in urine. Of the five proteins that were validated by ELISA, Sh-TSP-2 (area under the curve [AUC]serum=0·98 [95% CI 0·95–1·00]; AUCurine=0·96 [0·93–0·99]), and MS3_01370 (AUCserum=0·93 [0·89–0·97]; AUCurine=0·81 [0·72–0·89]) displayed the highest overall diagnostic performance in each biofluid and exceeded that of S haematobium-soluble egg antigen in urine (AUC=0·79 [0·69–0·90]). When incorporated into separate POC-ICTs, Sh-TSP-2 showed absolute specificity and a sensitivity of 75% and MS3_01370 showed absolute specificity and a sensitivity of 89%. Interpretation: We identified numerous biomarkers of urogenital schistosomiasis that could form the basis of novel antibody diagnostics for this disease. Two of these antigens, Sh-TSP-2 and MS3_01370, could be used as sensitive, specific, and field-deployable diagnostics to support schistosomiasis control and elimination initiatives, with particular focus on post-elimination surveillance. Funding: Australian Trade and Investment Commission and Merck Global Health Institute.
format	article
author	Mark S Pearson, PhD Bemnet A Tedla, PhD Gebeyaw G Mekonnen, PhD Carla Proietti, PhD Luke Becker, BSc Rie Nakajima, MSc Al Jasinskas, PhD Denise L Doolan, PhD Abena S Amoah, PhD Stefanie Knopp, PhD David Rollinson, PhD Said M Ali, MSc Fatma Kabole, MD Cornelis H Hokke, PhD Akim A Adegnika, MD Matt A Field, PhD Govert van Dam, PhD Paul L A M Corstjens, PhD Takafira Mduluza, PhD Francisca Mutapi, PhD Claude Oeuvray, PhD Beatrice Greco, PhD Sujittra Chaiyadet, PhD Thewarach Laha, PhD Pengfei Cai, PhD Donald P McManus, PhD Maria Elena Bottazzi, PhD Philip L Felgner, PhD Javier Sotillo, PhD Alex Loukas, PhD
author_facet	Mark S Pearson, PhD Bemnet A Tedla, PhD Gebeyaw G Mekonnen, PhD Carla Proietti, PhD Luke Becker, BSc Rie Nakajima, MSc Al Jasinskas, PhD Denise L Doolan, PhD Abena S Amoah, PhD Stefanie Knopp, PhD David Rollinson, PhD Said M Ali, MSc Fatma Kabole, MD Cornelis H Hokke, PhD Akim A Adegnika, MD Matt A Field, PhD Govert van Dam, PhD Paul L A M Corstjens, PhD Takafira Mduluza, PhD Francisca Mutapi, PhD Claude Oeuvray, PhD Beatrice Greco, PhD Sujittra Chaiyadet, PhD Thewarach Laha, PhD Pengfei Cai, PhD Donald P McManus, PhD Maria Elena Bottazzi, PhD Philip L Felgner, PhD Javier Sotillo, PhD Alex Loukas, PhD
author_sort	Mark S Pearson, PhD
title	Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study
title_short	Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study
title_full	Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study
title_fullStr	Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study
title_full_unstemmed	Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study
title_sort	immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e9c0510583ca4bf58360b82613221a36
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Immunomics-guided discovery of serum and urine antibodies for diagnosing urogenital schistosomiasis: a biomarker identification study

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