Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins
American tegumentary leishmaniasis (TL) caused by Leishmania braziliensis is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite c...
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| Veröffentlicht in: | Emerging microbes & infections 2022-12, Vol.11 (1), p.2147-2159 |
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| creator | Viana, Sayonara M. Montoya, Alba L. Carvalho, Augusto M. de Mendonça, Brunele S. Portillo, Susana Olivas, Janet J. Karimi, Nasim H. Estevao, Igor L. Ortega-Rodriguez, Uriel Carvalho, Edgar M. Dutra, Walderez O. Maldonaldo, Rosa A. Michael, Katja de Oliveira, Camila I. Almeida, Igor C. |
| description | American tegumentary leishmaniasis (TL) caused by Leishmania braziliensis is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of Leishmania-specific anti-α-Gal antibodies. However, the native parasite α-Gal glycotope(s) is(are) still elusive, thus they have not yet been explored for a more accurate TL diagnosis. Using a chemiluminescent immunoassay, we evaluated the seroreactivity of TL patients across its clinical spectrum, and of endemic (EC) and nonendemic healthy controls (NEC) against three synthetic neoglycoproteins (NGP29b, NGP30b, and NGP28b), respectively comprising the L. major-derived type-2 glycoinositolphospholipid (GIPL)-1 (Galfβ1,3Manα), GIPL-2 (Galα1,3Galfβ1,3Manα), and GIPL-3 (Galα1,6Galα1,3Galfβ) glycotopes. Contrary to NGP29b and NGP30b, NGP28b exhibited high sensitivity and specificity to a CL serum pool. More importantly, NGP28b reacted strongly and specifically with individual sera from distinct clinical forms of TL, especially with SC sera, with 94% sensitivity and 97% specificity, by post-two-graph receiver-operating characteristic curve analysis. Contrary to NGP29b, NGP28b showed low cross-reactivity with Chagas disease and control (NEC/EC) sera. Additionally, seroreactivity of CL patients against NGP28b was significantly decreased after successful chemotherapy, indicating that L. braziliensis-specific anti-α-Gal antibodies may serve as an early biomarker of cure in CL. Our data also points towards the applicability of L. major type-2 GIPL-3-derived Galα1,6Galα1,3Galfβ glycotope for the serological diagnosis of American TL, particularly of the subclinical form. |
| doi_str_mv | 10.1080/22221751.2022.2114852 |
| format | Article |
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Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of Leishmania-specific anti-α-Gal antibodies. However, the native parasite α-Gal glycotope(s) is(are) still elusive, thus they have not yet been explored for a more accurate TL diagnosis. Using a chemiluminescent immunoassay, we evaluated the seroreactivity of TL patients across its clinical spectrum, and of endemic (EC) and nonendemic healthy controls (NEC) against three synthetic neoglycoproteins (NGP29b, NGP30b, and NGP28b), respectively comprising the L. major-derived type-2 glycoinositolphospholipid (GIPL)-1 (Galfβ1,3Manα), GIPL-2 (Galα1,3Galfβ1,3Manα), and GIPL-3 (Galα1,6Galα1,3Galfβ) glycotopes. Contrary to NGP29b and NGP30b, NGP28b exhibited high sensitivity and specificity to a CL serum pool. More importantly, NGP28b reacted strongly and specifically with individual sera from distinct clinical forms of TL, especially with SC sera, with 94% sensitivity and 97% specificity, by post-two-graph receiver-operating characteristic curve analysis. Contrary to NGP29b, NGP28b showed low cross-reactivity with Chagas disease and control (NEC/EC) sera. Additionally, seroreactivity of CL patients against NGP28b was significantly decreased after successful chemotherapy, indicating that L. braziliensis-specific anti-α-Gal antibodies may serve as an early biomarker of cure in CL. Our data also points towards the applicability of L. major type-2 GIPL-3-derived Galα1,6Galα1,3Galfβ glycotope for the serological diagnosis of American TL, particularly of the subclinical form.</description><identifier>ISSN: 2222-1751</identifier><identifier>EISSN: 2222-1751</identifier><identifier>DOI: 10.1080/22221751.2022.2114852</identifier><identifier>PMID: 36039908</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>anti-α-Gal antibodies ; Antibodies ; Antigens ; Asymptomatic ; Biomarkers ; Biomedical research ; Chemotherapy ; diagnostic and prognostic biomarkers ; Glycoproteins ; Humans ; Infections ; Laboratories ; Leishmania braziliensis ; Leishmaniasis, Cutaneous ; Parasites ; Parasitic diseases ; Serologic Tests ; Serology ; Skin ; tegumentary leishmaniasis ; Tropical diseases ; α-Gal neoglycoproteins</subject><ispartof>Emerging microbes & infections, 2022-12, Vol.11 (1), p.2147-2159</ispartof><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-1ae880093a74afd378b50bc1c081498e15d3e596cf3dc42b382eb49156eea6383</citedby><cites>FETCH-LOGICAL-c562t-1ae880093a74afd378b50bc1c081498e15d3e596cf3dc42b382eb49156eea6383</cites><orcidid>0000-0001-6754-3702 ; 0000-0002-1700-357X ; 0000-0003-3946-8375 ; 0000-0002-2443-8213 ; 0000-0002-7868-5164 ; 0000-0002-7586-9996 ; 0000-0002-1803-1564 ; 0000-0002-5210-0797 ; 0000-0002-1473-1299</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518598/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9518598/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,27507,27929,27930,53796,53798,59148,59149</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36039908$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Viana, Sayonara M.</creatorcontrib><creatorcontrib>Montoya, Alba L.</creatorcontrib><creatorcontrib>Carvalho, Augusto M.</creatorcontrib><creatorcontrib>de Mendonça, Brunele S.</creatorcontrib><creatorcontrib>Portillo, Susana</creatorcontrib><creatorcontrib>Olivas, Janet J.</creatorcontrib><creatorcontrib>Karimi, Nasim H.</creatorcontrib><creatorcontrib>Estevao, Igor L.</creatorcontrib><creatorcontrib>Ortega-Rodriguez, Uriel</creatorcontrib><creatorcontrib>Carvalho, Edgar M.</creatorcontrib><creatorcontrib>Dutra, Walderez O.</creatorcontrib><creatorcontrib>Maldonaldo, Rosa A.</creatorcontrib><creatorcontrib>Michael, Katja</creatorcontrib><creatorcontrib>de Oliveira, Camila I.</creatorcontrib><creatorcontrib>Almeida, Igor C.</creatorcontrib><title>Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins</title><title>Emerging microbes & infections</title><addtitle>Emerg Microbes Infect</addtitle><description>American tegumentary leishmaniasis (TL) caused by Leishmania braziliensis is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of Leishmania-specific anti-α-Gal antibodies. However, the native parasite α-Gal glycotope(s) is(are) still elusive, thus they have not yet been explored for a more accurate TL diagnosis. Using a chemiluminescent immunoassay, we evaluated the seroreactivity of TL patients across its clinical spectrum, and of endemic (EC) and nonendemic healthy controls (NEC) against three synthetic neoglycoproteins (NGP29b, NGP30b, and NGP28b), respectively comprising the L. major-derived type-2 glycoinositolphospholipid (GIPL)-1 (Galfβ1,3Manα), GIPL-2 (Galα1,3Galfβ1,3Manα), and GIPL-3 (Galα1,6Galα1,3Galfβ) glycotopes. Contrary to NGP29b and NGP30b, NGP28b exhibited high sensitivity and specificity to a CL serum pool. More importantly, NGP28b reacted strongly and specifically with individual sera from distinct clinical forms of TL, especially with SC sera, with 94% sensitivity and 97% specificity, by post-two-graph receiver-operating characteristic curve analysis. Contrary to NGP29b, NGP28b showed low cross-reactivity with Chagas disease and control (NEC/EC) sera. Additionally, seroreactivity of CL patients against NGP28b was significantly decreased after successful chemotherapy, indicating that L. braziliensis-specific anti-α-Gal antibodies may serve as an early biomarker of cure in CL. Our data also points towards the applicability of L. major type-2 GIPL-3-derived Galα1,6Galα1,3Galfβ glycotope for the serological diagnosis of American TL, particularly of the subclinical form.</description><subject>anti-α-Gal antibodies</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Asymptomatic</subject><subject>Biomarkers</subject><subject>Biomedical research</subject><subject>Chemotherapy</subject><subject>diagnostic and prognostic biomarkers</subject><subject>Glycoproteins</subject><subject>Humans</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Leishmania braziliensis</subject><subject>Leishmaniasis, Cutaneous</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Serologic Tests</subject><subject>Serology</subject><subject>Skin</subject><subject>tegumentary leishmaniasis</subject><subject>Tropical diseases</subject><subject>α-Gal 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and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins</title><author>Viana, Sayonara M. ; Montoya, Alba L. ; Carvalho, Augusto M. ; de Mendonça, Brunele S. ; Portillo, Susana ; Olivas, Janet J. ; Karimi, Nasim H. ; Estevao, Igor L. ; Ortega-Rodriguez, Uriel ; Carvalho, Edgar M. ; Dutra, Walderez O. ; Maldonaldo, Rosa A. ; Michael, Katja ; de Oliveira, Camila I. ; Almeida, Igor C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-1ae880093a74afd378b50bc1c081498e15d3e596cf3dc42b382eb49156eea6383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>anti-α-Gal antibodies</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Asymptomatic</topic><topic>Biomarkers</topic><topic>Biomedical research</topic><topic>Chemotherapy</topic><topic>diagnostic and prognostic 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infections</jtitle><addtitle>Emerg Microbes Infect</addtitle><date>2022-12</date><risdate>2022</risdate><volume>11</volume><issue>1</issue><spage>2147</spage><epage>2159</epage><pages>2147-2159</pages><issn>2222-1751</issn><eissn>2222-1751</eissn><abstract>American tegumentary leishmaniasis (TL) caused by Leishmania braziliensis is characterized by a spectrum of clinical presentations, ranging from localized cutaneous ulcers (CL), mucosal (ML), or disseminated (DL) disease, to a subclinical (SC) asymptomatic form. Current diagnosis based on parasite culture and/or microscopy lacks sensitivity and specificity. Previous studies showed that patients with CL and ML have very high levels of Leishmania-specific anti-α-Gal antibodies. However, the native parasite α-Gal glycotope(s) is(are) still elusive, thus they have not yet been explored for a more accurate TL diagnosis. Using a chemiluminescent immunoassay, we evaluated the seroreactivity of TL patients across its clinical spectrum, and of endemic (EC) and nonendemic healthy controls (NEC) against three synthetic neoglycoproteins (NGP29b, NGP30b, and NGP28b), respectively comprising the L. major-derived type-2 glycoinositolphospholipid (GIPL)-1 (Galfβ1,3Manα), GIPL-2 (Galα1,3Galfβ1,3Manα), and GIPL-3 (Galα1,6Galα1,3Galfβ) glycotopes. Contrary to NGP29b and NGP30b, NGP28b exhibited high sensitivity and specificity to a CL serum pool. More importantly, NGP28b reacted strongly and specifically with individual sera from distinct clinical forms of TL, especially with SC sera, with 94% sensitivity and 97% specificity, by post-two-graph receiver-operating characteristic curve analysis. Contrary to NGP29b, NGP28b showed low cross-reactivity with Chagas disease and control (NEC/EC) sera. Additionally, seroreactivity of CL patients against NGP28b was significantly decreased after successful chemotherapy, indicating that L. braziliensis-specific anti-α-Gal antibodies may serve as an early biomarker of cure in CL. 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| language | eng |
| recordid | cdi_proquest_journals_2748035033 |
| source | Open Access: PubMed Central; MEDLINE; DOAJ Directory of Open Access Journals; Taylor & Francis (Open access); EZB Electronic Journals Library |
| subjects | anti-α-Gal antibodies Antibodies Antigens Asymptomatic Biomarkers Biomedical research Chemotherapy diagnostic and prognostic biomarkers Glycoproteins Humans Infections Laboratories Leishmania braziliensis Leishmaniasis, Cutaneous Parasites Parasitic diseases Serologic Tests Serology Skin tegumentary leishmaniasis Tropical diseases α-Gal neoglycoproteins |
| title | Serodiagnosis and therapeutic monitoring of New-World tegumentary leishmaniasis using synthetic type-2 glycoinositolphospholipid-based neoglycoproteins |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-13T21%3A56%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Serodiagnosis%20and%20therapeutic%20monitoring%20of%20New-World%20tegumentary%20leishmaniasis%20using%20synthetic%20type-2%20glycoinositolphospholipid-based%20neoglycoproteins&rft.jtitle=Emerging%20microbes%20&%20infections&rft.au=Viana,%20Sayonara%20M.&rft.date=2022-12&rft.volume=11&rft.issue=1&rft.spage=2147&rft.epage=2159&rft.pages=2147-2159&rft.issn=2222-1751&rft.eissn=2222-1751&rft_id=info:doi/10.1080/22221751.2022.2114852&rft_dat=%3Cproquest_pubme%3E2708261932%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2748035033&rft_id=info:pmid/36039908&rft_doaj_id=oai_doaj_org_article_bfa95462ae3e4777815af48ad947136e&rfr_iscdi=true |