StaphAIR: A Label-Free Antigen Microarray Approach to Detecting Anti-Staphylococcus aureus Antibody Responses in Orthopedic Infections
Arrayed imaging reflectometry (AIR) is an optical biosensor platform for simple, multiplex measurement of antigen-specific antibody responses in patient blood samples. Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen...
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Veröffentlicht in: | Analytical chemistry (Washington) 2021-10, Vol.93 (40), p.13580-13588 |
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creator | Klose, Alanna M Daiss, John L Ho, Lananh Beck, Christopher A Striemer, Christopher C Muthukrishnan, Gowrishankar Miller, Benjamin L |
description | Arrayed imaging reflectometry (AIR) is an optical biosensor platform for simple, multiplex measurement of antigen-specific antibody responses in patient blood samples. Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen-specific anti-S. aureus humoral immune responses. Initial validation experiments with mouse and humanized monoclonal antibodies against the S. aureus autolysin glucosaminidase (Gmd) domain, and subsequent testing with dilution series of pooled positive human serum confirmed analytically robust behavior of the array, with all antigens displaying Langmuir-type dose–response curves. Testing a cohort of 82 patients with S. aureus musculoskeletal infections (MSKI) and 30 healthy individuals enabled discrimination of individual patient responses to different S. aureus antigens, with statistical significance between osteomyelitis patients and controls obtained overall for four individual antigens (IsdA, IsdB, Gmd, and SCIN). Multivariate analyses of the antibody titers obtained from StaphAIR revealed its utility as a potential diagnostic tool for detecting S. aureus MSKI (area under the receiver operating characteristic curve (AUC) > 0.85). We conclude that StaphAIR has utility as a high-throughput immunoassay for studying and diagnosing osteomyelitis in patients. |
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Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen-specific anti-S. aureus humoral immune responses. Initial validation experiments with mouse and humanized monoclonal antibodies against the S. aureus autolysin glucosaminidase (Gmd) domain, and subsequent testing with dilution series of pooled positive human serum confirmed analytically robust behavior of the array, with all antigens displaying Langmuir-type dose–response curves. Testing a cohort of 82 patients with S. aureus musculoskeletal infections (MSKI) and 30 healthy individuals enabled discrimination of individual patient responses to different S. aureus antigens, with statistical significance between osteomyelitis patients and controls obtained overall for four individual antigens (IsdA, IsdB, Gmd, and SCIN). Multivariate analyses of the antibody titers obtained from StaphAIR revealed its utility as a potential diagnostic tool for detecting S. aureus MSKI (area under the receiver operating characteristic curve (AUC) > 0.85). We conclude that StaphAIR has utility as a high-throughput immunoassay for studying and diagnosing osteomyelitis in patients.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.1c02658</identifier><language>eng</language><publisher>Washington: American Chemical Society</publisher><subject>Antibodies ; Antigens ; Arrays ; Biomedical materials ; Biosensors ; Chemistry ; Dilution ; Glucosaminidase ; Immune response (humoral) ; Immunoassay ; Infections ; Monoclonal antibodies ; Orthopedics ; Osteomyelitis ; Patients ; Penicillin ; Staphylococcus aureus ; Statistical methods</subject><ispartof>Analytical chemistry (Washington), 2021-10, Vol.93 (40), p.13580-13588</ispartof><rights>2021 American Chemical Society</rights><rights>Copyright American Chemical Society Oct 12, 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a283t-ed5ba3198af1238d3d000f4b29f050a6a441d0978f66ce04d0f235107d93b75b3</citedby><cites>FETCH-LOGICAL-a283t-ed5ba3198af1238d3d000f4b29f050a6a441d0978f66ce04d0f235107d93b75b3</cites><orcidid>0000-0001-9168-8047</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.analchem.1c02658$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.analchem.1c02658$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids></links><search><creatorcontrib>Klose, Alanna M</creatorcontrib><creatorcontrib>Daiss, John L</creatorcontrib><creatorcontrib>Ho, Lananh</creatorcontrib><creatorcontrib>Beck, Christopher A</creatorcontrib><creatorcontrib>Striemer, Christopher C</creatorcontrib><creatorcontrib>Muthukrishnan, Gowrishankar</creatorcontrib><creatorcontrib>Miller, Benjamin L</creatorcontrib><title>StaphAIR: A Label-Free Antigen Microarray Approach to Detecting Anti-Staphylococcus aureus Antibody Responses in Orthopedic Infections</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>Arrayed imaging reflectometry (AIR) is an optical biosensor platform for simple, multiplex measurement of antigen-specific antibody responses in patient blood samples. Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen-specific anti-S. aureus humoral immune responses. Initial validation experiments with mouse and humanized monoclonal antibodies against the S. aureus autolysin glucosaminidase (Gmd) domain, and subsequent testing with dilution series of pooled positive human serum confirmed analytically robust behavior of the array, with all antigens displaying Langmuir-type dose–response curves. Testing a cohort of 82 patients with S. aureus musculoskeletal infections (MSKI) and 30 healthy individuals enabled discrimination of individual patient responses to different S. aureus antigens, with statistical significance between osteomyelitis patients and controls obtained overall for four individual antigens (IsdA, IsdB, Gmd, and SCIN). Multivariate analyses of the antibody titers obtained from StaphAIR revealed its utility as a potential diagnostic tool for detecting S. aureus MSKI (area under the receiver operating characteristic curve (AUC) > 0.85). We conclude that StaphAIR has utility as a high-throughput immunoassay for studying and diagnosing osteomyelitis in patients.</description><subject>Antibodies</subject><subject>Antigens</subject><subject>Arrays</subject><subject>Biomedical materials</subject><subject>Biosensors</subject><subject>Chemistry</subject><subject>Dilution</subject><subject>Glucosaminidase</subject><subject>Immune response (humoral)</subject><subject>Immunoassay</subject><subject>Infections</subject><subject>Monoclonal antibodies</subject><subject>Orthopedics</subject><subject>Osteomyelitis</subject><subject>Patients</subject><subject>Penicillin</subject><subject>Staphylococcus aureus</subject><subject>Statistical methods</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9kc1u2zAQhImgAeI6eYMcCOTSi5xdUj90b0IatwYcBMjPWaCoVaxAFlVSOugF-tyl4qSHHnLaBeabAXaHsUuEFYLAa238Sne6NXs6rNCASBN1whaYCIhSpcQXtgAAGYkM4Ix99f4VABEwXbA_j4Pu9_n24TvP-U6X1EYbR8TzbmheqON3jXFWO6cnnvd9WM2eD5b_oIHM0HQvb2D0FjK11lhjRs_16CiMWSptNfEH8r3tPHnedPzeDXvbU9UYvu3qOSVI5-y01q2ni_e5ZM-b26ebX9Hu_uf2Jt9FWig5RFQlpZa4VrpGIVUlq3BXHZdiXUMCOtVxjBWsM1WnqSGIK6iFTBCyai3LLCnlkn075oZTfo_kh-LQeENtqzuyoy9EkqlMIUgM6NV_6KsdXfjyTCmJmAHGgYqPVHiT947qonfNQbupQCjmcopQTvFRTvFeTrDB0Tar_3I_tfwF0CaWuw</recordid><startdate>20211012</startdate><enddate>20211012</enddate><creator>Klose, Alanna M</creator><creator>Daiss, John L</creator><creator>Ho, Lananh</creator><creator>Beck, Christopher A</creator><creator>Striemer, Christopher C</creator><creator>Muthukrishnan, Gowrishankar</creator><creator>Miller, Benjamin L</creator><general>American Chemical Society</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9168-8047</orcidid></search><sort><creationdate>20211012</creationdate><title>StaphAIR: A Label-Free Antigen Microarray Approach to Detecting Anti-Staphylococcus aureus Antibody Responses in Orthopedic Infections</title><author>Klose, Alanna M ; Daiss, John L ; Ho, Lananh ; Beck, Christopher A ; Striemer, Christopher C ; Muthukrishnan, Gowrishankar ; Miller, Benjamin L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a283t-ed5ba3198af1238d3d000f4b29f050a6a441d0978f66ce04d0f235107d93b75b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Antigens</topic><topic>Arrays</topic><topic>Biomedical materials</topic><topic>Biosensors</topic><topic>Chemistry</topic><topic>Dilution</topic><topic>Glucosaminidase</topic><topic>Immune response (humoral)</topic><topic>Immunoassay</topic><topic>Infections</topic><topic>Monoclonal antibodies</topic><topic>Orthopedics</topic><topic>Osteomyelitis</topic><topic>Patients</topic><topic>Penicillin</topic><topic>Staphylococcus aureus</topic><topic>Statistical methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klose, Alanna M</creatorcontrib><creatorcontrib>Daiss, John L</creatorcontrib><creatorcontrib>Ho, Lananh</creatorcontrib><creatorcontrib>Beck, Christopher A</creatorcontrib><creatorcontrib>Striemer, Christopher C</creatorcontrib><creatorcontrib>Muthukrishnan, Gowrishankar</creatorcontrib><creatorcontrib>Miller, Benjamin L</creatorcontrib><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Analytical chemistry (Washington)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klose, Alanna M</au><au>Daiss, John L</au><au>Ho, Lananh</au><au>Beck, Christopher A</au><au>Striemer, Christopher C</au><au>Muthukrishnan, Gowrishankar</au><au>Miller, Benjamin L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>StaphAIR: A Label-Free Antigen Microarray Approach to Detecting Anti-Staphylococcus aureus Antibody Responses in Orthopedic Infections</atitle><jtitle>Analytical chemistry (Washington)</jtitle><addtitle>Anal. Chem</addtitle><date>2021-10-12</date><risdate>2021</risdate><volume>93</volume><issue>40</issue><spage>13580</spage><epage>13588</epage><pages>13580-13588</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><abstract>Arrayed imaging reflectometry (AIR) is an optical biosensor platform for simple, multiplex measurement of antigen-specific antibody responses in patient blood samples. Here, we report the development of StaphAIR, an 8-plex Staphylococcus aureus antigen array on the AIR platform for profiling antigen-specific anti-S. aureus humoral immune responses. Initial validation experiments with mouse and humanized monoclonal antibodies against the S. aureus autolysin glucosaminidase (Gmd) domain, and subsequent testing with dilution series of pooled positive human serum confirmed analytically robust behavior of the array, with all antigens displaying Langmuir-type dose–response curves. Testing a cohort of 82 patients with S. aureus musculoskeletal infections (MSKI) and 30 healthy individuals enabled discrimination of individual patient responses to different S. aureus antigens, with statistical significance between osteomyelitis patients and controls obtained overall for four individual antigens (IsdA, IsdB, Gmd, and SCIN). Multivariate analyses of the antibody titers obtained from StaphAIR revealed its utility as a potential diagnostic tool for detecting S. aureus MSKI (area under the receiver operating characteristic curve (AUC) > 0.85). We conclude that StaphAIR has utility as a high-throughput immunoassay for studying and diagnosing osteomyelitis in patients.</abstract><cop>Washington</cop><pub>American Chemical Society</pub><doi>10.1021/acs.analchem.1c02658</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9168-8047</orcidid></addata></record> |
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subjects | Antibodies Antigens Arrays Biomedical materials Biosensors Chemistry Dilution Glucosaminidase Immune response (humoral) Immunoassay Infections Monoclonal antibodies Orthopedics Osteomyelitis Patients Penicillin Staphylococcus aureus Statistical methods |
title | StaphAIR: A Label-Free Antigen Microarray Approach to Detecting Anti-Staphylococcus aureus Antibody Responses in Orthopedic Infections |
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