High-throughput epitope profiling of antibodies in the plasma of Alzheimer’s disease patients using random peptide microarrays
The symptoms of Alzheimer’s disease (AD), a major cause of dementia in older adults, are linked directly with neuronal cell death, which is thought to be due to aberrant neuronal inflammation. Autoantibodies formed during neuronal inflammation show excellent stability in blood; therefore, they may b...
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| Veröffentlicht in: | Scientific reports 2019-03, Vol.9 (1), p.4587-4587, Article 4587 |
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| creator | Sim, Kyu-Young Park, Sang-Heon Choi, Kyu Yeong Park, Jung Eun Lee, Jung Sup Kim, Byeong C. Gwak, Jeonghwan Song, Woo Keun Lee, Kun Ho Park, Sung-Gyoo |
| description | The symptoms of Alzheimer’s disease (AD), a major cause of dementia in older adults, are linked directly with neuronal cell death, which is thought to be due to aberrant neuronal inflammation. Autoantibodies formed during neuronal inflammation show excellent stability in blood; therefore, they may be convenient blood-based diagnostic markers of AD. Here, we performed microarray analysis of 29,240 unbiased random peptides to be used for comprehensive screening of AD-specific IgG and IgM antibodies in the blood. The results showed that (1) sequence-specific and isotype-specific antibodies are regulated differentially in AD, and combinations of these antibodies showing high area under the receiver operating characteristic curve values (0.862–0.961) can be used to classify AD, (2) AD-specific IgG antibodies arise from IgM antibody-secreting cells that existed before disease onset and (3) target protein profiling of the antibodies identified some AD-related proteins, some of which are involved in AD-related signalling pathways. Therefore, we propose that these epitopes may facilitate the development of biomarkers for AD diagnosis and form the basis for a mechanistic study related to AD progression. |
| doi_str_mv | 10.1038/s41598-019-40976-x |
| format | Article |
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Autoantibodies formed during neuronal inflammation show excellent stability in blood; therefore, they may be convenient blood-based diagnostic markers of AD. Here, we performed microarray analysis of 29,240 unbiased random peptides to be used for comprehensive screening of AD-specific IgG and IgM antibodies in the blood. The results showed that (1) sequence-specific and isotype-specific antibodies are regulated differentially in AD, and combinations of these antibodies showing high area under the receiver operating characteristic curve values (0.862–0.961) can be used to classify AD, (2) AD-specific IgG antibodies arise from IgM antibody-secreting cells that existed before disease onset and (3) target protein profiling of the antibodies identified some AD-related proteins, some of which are involved in AD-related signalling pathways. Therefore, we propose that these epitopes may facilitate the development of biomarkers for AD diagnosis and form the basis for a mechanistic study related to AD progression.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-40976-x</identifier><identifier>PMID: 30872784</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/1 ; 45/61 ; 631/250/256/2515 ; 692/53/2421 ; 96/47 ; Alzheimer Disease - blood ; Alzheimer Disease - diagnosis ; Alzheimer Disease - immunology ; Alzheimer's disease ; Autoantibodies ; Autoantibodies - blood ; Autoantibodies - immunology ; Biomarkers ; Blood ; Cell death ; Computational Biology ; Dementia disorders ; Epitope Mapping ; Epitopes ; Epitopes - immunology ; Female ; High-Throughput Screening Assays ; Humanities and Social Sciences ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Male ; multidisciplinary ; Older people ; Peptides ; Peptides - immunology ; Protein Array Analysis ; ROC Curve ; Science ; Science (multidisciplinary) ; Signal Transduction</subject><ispartof>Scientific reports, 2019-03, Vol.9 (1), p.4587-4587, Article 4587</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-e84a7672462dd87eab50dd2c25d307115d6a1b6aef0b1519115e6e0c18ea3d6c3</citedby><cites>FETCH-LOGICAL-c474t-e84a7672462dd87eab50dd2c25d307115d6a1b6aef0b1519115e6e0c18ea3d6c3</cites><orcidid>0000-0003-3702-5765</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/PMC6418098/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418098/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30872784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sim, Kyu-Young</creatorcontrib><creatorcontrib>Park, Sang-Heon</creatorcontrib><creatorcontrib>Choi, Kyu Yeong</creatorcontrib><creatorcontrib>Park, Jung Eun</creatorcontrib><creatorcontrib>Lee, Jung Sup</creatorcontrib><creatorcontrib>Kim, Byeong C.</creatorcontrib><creatorcontrib>Gwak, Jeonghwan</creatorcontrib><creatorcontrib>Song, Woo Keun</creatorcontrib><creatorcontrib>Lee, Kun Ho</creatorcontrib><creatorcontrib>Park, Sung-Gyoo</creatorcontrib><title>High-throughput epitope profiling of antibodies in the plasma of Alzheimer’s disease patients using random peptide microarrays</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>The symptoms of Alzheimer’s disease (AD), a major cause of dementia in older adults, are linked directly with neuronal cell death, which is thought to be due to aberrant neuronal inflammation. Autoantibodies formed during neuronal inflammation show excellent stability in blood; therefore, they may be convenient blood-based diagnostic markers of AD. Here, we performed microarray analysis of 29,240 unbiased random peptides to be used for comprehensive screening of AD-specific IgG and IgM antibodies in the blood. The results showed that (1) sequence-specific and isotype-specific antibodies are regulated differentially in AD, and combinations of these antibodies showing high area under the receiver operating characteristic curve values (0.862–0.961) can be used to classify AD, (2) AD-specific IgG antibodies arise from IgM antibody-secreting cells that existed before disease onset and (3) target protein profiling of the antibodies identified some AD-related proteins, some of which are involved in AD-related signalling pathways. Therefore, we propose that these epitopes may facilitate the development of biomarkers for AD diagnosis and form the basis for a mechanistic study related to AD progression.</description><subject>14/1</subject><subject>45/61</subject><subject>631/250/256/2515</subject><subject>692/53/2421</subject><subject>96/47</subject><subject>Alzheimer Disease - blood</subject><subject>Alzheimer Disease - diagnosis</subject><subject>Alzheimer Disease - immunology</subject><subject>Alzheimer's disease</subject><subject>Autoantibodies</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - immunology</subject><subject>Biomarkers</subject><subject>Blood</subject><subject>Cell death</subject><subject>Computational Biology</subject><subject>Dementia disorders</subject><subject>Epitope Mapping</subject><subject>Epitopes</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>High-Throughput Screening Assays</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulins</subject><subject>Male</subject><subject>multidisciplinary</subject><subject>Older people</subject><subject>Peptides</subject><subject>Peptides - immunology</subject><subject>Protein Array Analysis</subject><subject>ROC Curve</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Signal Transduction</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kb9u1jAUxS0EolXpCzAgSywsKf4XO1mQqgooUiUWmC0nvklcJXawHdR26mvwejwJ_vqVUhjwYsvnd4_v9UHoJSUnlPDmbRK0bpuK0LYSpFWyunqCDhkRdcU4Y08fnQ_QcUqXpKyatYK2z9EBJ41iqhGH6PbcjVOVpxi2cVq3jGF1OayA1xgGNzs_4jBg47PrgnWQsPM4T0WeTVrMTjudbyZwC8Sftz8Sti6BSUU32YHPCW9p5xGNt2HBK6zZWcCL62MwMZrr9AI9G8yc4Ph-P0JfP7z_cnZeXXz--Ons9KLqhRK5gkYYJRUTklnbKDBdTaxlPastJ4rS2kpDO2lgIB2taVtuQALpaQOGW9nzI_Ru77tu3QK2L81FM-s1usXEax2M038r3k16DN-1FLQhbVMM3twbxPBtg5T14lIP82w8hC1pRltOpeCEFPT1P-hl2KIv4-0oyutaMVkotqfKX6QUYXhohhK9y1jvM9YlY32Xsb4qRa8ej_FQ8jvRAvA9kIrkR4h_3v6P7S8v_rcH</recordid><startdate>20190314</startdate><enddate>20190314</enddate><creator>Sim, Kyu-Young</creator><creator>Park, Sang-Heon</creator><creator>Choi, Kyu Yeong</creator><creator>Park, Jung Eun</creator><creator>Lee, Jung Sup</creator><creator>Kim, Byeong C.</creator><creator>Gwak, Jeonghwan</creator><creator>Song, Woo Keun</creator><creator>Lee, Kun Ho</creator><creator>Park, Sung-Gyoo</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3702-5765</orcidid></search><sort><creationdate>20190314</creationdate><title>High-throughput epitope profiling of antibodies in the plasma of Alzheimer’s disease patients using random peptide microarrays</title><author>Sim, Kyu-Young ; Park, Sang-Heon ; Choi, Kyu Yeong ; Park, Jung Eun ; Lee, Jung Sup ; Kim, Byeong C. ; Gwak, Jeonghwan ; Song, Woo Keun ; Lee, Kun Ho ; Park, Sung-Gyoo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-e84a7672462dd87eab50dd2c25d307115d6a1b6aef0b1519115e6e0c18ea3d6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>14/1</topic><topic>45/61</topic><topic>631/250/256/2515</topic><topic>692/53/2421</topic><topic>96/47</topic><topic>Alzheimer Disease - blood</topic><topic>Alzheimer Disease - diagnosis</topic><topic>Alzheimer Disease - immunology</topic><topic>Alzheimer's disease</topic><topic>Autoantibodies</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - immunology</topic><topic>Biomarkers</topic><topic>Blood</topic><topic>Cell death</topic><topic>Computational Biology</topic><topic>Dementia disorders</topic><topic>Epitope Mapping</topic><topic>Epitopes</topic><topic>Epitopes - immunology</topic><topic>Female</topic><topic>High-Throughput Screening Assays</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin M</topic><topic>Immunoglobulins</topic><topic>Male</topic><topic>multidisciplinary</topic><topic>Older people</topic><topic>Peptides</topic><topic>Peptides - immunology</topic><topic>Protein Array Analysis</topic><topic>ROC Curve</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sim, Kyu-Young</creatorcontrib><creatorcontrib>Park, Sang-Heon</creatorcontrib><creatorcontrib>Choi, Kyu Yeong</creatorcontrib><creatorcontrib>Park, Jung Eun</creatorcontrib><creatorcontrib>Lee, Jung Sup</creatorcontrib><creatorcontrib>Kim, Byeong C.</creatorcontrib><creatorcontrib>Gwak, Jeonghwan</creatorcontrib><creatorcontrib>Song, Woo Keun</creatorcontrib><creatorcontrib>Lee, Kun Ho</creatorcontrib><creatorcontrib>Park, Sung-Gyoo</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sim, Kyu-Young</au><au>Park, Sang-Heon</au><au>Choi, Kyu Yeong</au><au>Park, Jung Eun</au><au>Lee, Jung Sup</au><au>Kim, Byeong C.</au><au>Gwak, Jeonghwan</au><au>Song, Woo Keun</au><au>Lee, Kun Ho</au><au>Park, Sung-Gyoo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High-throughput epitope profiling of antibodies in the plasma of Alzheimer’s disease patients using random peptide microarrays</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-03-14</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>4587</spage><epage>4587</epage><pages>4587-4587</pages><artnum>4587</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>The symptoms of Alzheimer’s disease (AD), a major cause of dementia in older adults, are linked directly with neuronal cell death, which is thought to be due to aberrant neuronal inflammation. Autoantibodies formed during neuronal inflammation show excellent stability in blood; therefore, they may be convenient blood-based diagnostic markers of AD. Here, we performed microarray analysis of 29,240 unbiased random peptides to be used for comprehensive screening of AD-specific IgG and IgM antibodies in the blood. The results showed that (1) sequence-specific and isotype-specific antibodies are regulated differentially in AD, and combinations of these antibodies showing high area under the receiver operating characteristic curve values (0.862–0.961) can be used to classify AD, (2) AD-specific IgG antibodies arise from IgM antibody-secreting cells that existed before disease onset and (3) target protein profiling of the antibodies identified some AD-related proteins, some of which are involved in AD-related signalling pathways. Therefore, we propose that these epitopes may facilitate the development of biomarkers for AD diagnosis and form the basis for a mechanistic study related to AD progression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30872784</pmid><doi>10.1038/s41598-019-40976-x</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-3702-5765</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 14/1 45/61 631/250/256/2515 692/53/2421 96/47 Alzheimer Disease - blood Alzheimer Disease - diagnosis Alzheimer Disease - immunology Alzheimer's disease Autoantibodies Autoantibodies - blood Autoantibodies - immunology Biomarkers Blood Cell death Computational Biology Dementia disorders Epitope Mapping Epitopes Epitopes - immunology Female High-Throughput Screening Assays Humanities and Social Sciences Humans Immunoglobulin G Immunoglobulin M Immunoglobulins Male multidisciplinary Older people Peptides Peptides - immunology Protein Array Analysis ROC Curve Science Science (multidisciplinary) Signal Transduction |
| title | High-throughput epitope profiling of antibodies in the plasma of Alzheimer’s disease patients using random peptide microarrays |
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