Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis
Background and objective: Acute disseminated encephalomyelitis (ADEM) and relapsing–remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantib...
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| Veröffentlicht in: | Multiple sclerosis 2013-11, Vol.19 (13), p.1726-1733 |
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| creator | Van Haren, Keith Tomooka, Beren H Kidd, Brian A Banwell, Brenda Bar-Or, Amit Chitnis, Tanuja Tenembaum, Silvia N Pohl, Daniela Rostasy, Kevin Dale, Russell C O’Connor, Kevin C Hafler, David A Steinman, Lawrence Robinson, William H |
| description | Background and objective:
Acute disseminated encephalomyelitis (ADEM) and relapsing–remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them.
Methods:
We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles.
Results:
ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62–86%; specificity 56–79%) from MS serum (sensitivity 40–87%; specificity 62–86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides.
Conclusions:
Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies. |
| doi_str_mv | 10.1177/1352458513485653 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4411183</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_1352458513485653</sage_id><sourcerecordid>3124214491</sourcerecordid><originalsourceid>FETCH-LOGICAL-c492t-8eed867f52afe525d0153725918ccfb47e527cffe0915c8f7611e6471865c4d53</originalsourceid><addsrcrecordid>eNp1kc9u1DAQxiMEoqVw54QsISQuAU9ix84FCVXlj1SJA3COvM5415VjB9up1Bs3HqBvyJPgsEsplTjZnvl934xnquop0FcAQryGljeMSw4tk7zj7b3qGJgQNe0FvV_uJV2v-aPqUUoXlFIhWv6wOmraDhop-uPqx2eMy0TUkoPy2W7CaDGRHMh0hc56MuOc7VhCo03Z-u1i044ovWRcIwkn61XGkaDXOO-UC7912SZiYphIRKfmVHQ_v1-Xx2TzakKmxWU7OyRJO4wh2fS4emCUS_jkcJ5UX9-dfTn9UJ9_ev_x9O15rVnf5FoijrIThjfKIG_4SIG3ouE9SK3NhokSFNoYpD1wLY3oALBjAmTHNRt5e1K92fvOy2bCUaPPUblhjnZS8WoIyg7_ZrzdDdtwOTAGALItBi8PBjF8WzDlYbJJo3PKY1jSAGXeIFmpX9Dnd9CLsERfvrdSlLbQcFEouqd0GUSKaG6aATqsWx7ubrlInt3-xI3gz1oL8OIAqKSVM1F5bdNfTpR5CSoLV--5pLZ4q7v_Ff4FZ03BcQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1450031257</pqid></control><display><type>article</type><title>Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis</title><source>MEDLINE</source><source>SAGE Complete</source><creator>Van Haren, Keith ; Tomooka, Beren H ; Kidd, Brian A ; Banwell, Brenda ; Bar-Or, Amit ; Chitnis, Tanuja ; Tenembaum, Silvia N ; Pohl, Daniela ; Rostasy, Kevin ; Dale, Russell C ; O’Connor, Kevin C ; Hafler, David A ; Steinman, Lawrence ; Robinson, William H</creator><creatorcontrib>Van Haren, Keith ; Tomooka, Beren H ; Kidd, Brian A ; Banwell, Brenda ; Bar-Or, Amit ; Chitnis, Tanuja ; Tenembaum, Silvia N ; Pohl, Daniela ; Rostasy, Kevin ; Dale, Russell C ; O’Connor, Kevin C ; Hafler, David A ; Steinman, Lawrence ; Robinson, William H</creatorcontrib><description>Background and objective:
Acute disseminated encephalomyelitis (ADEM) and relapsing–remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them.
Methods:
We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles.
Results:
ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62–86%; specificity 56–79%) from MS serum (sensitivity 40–87%; specificity 62–86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides.
Conclusions:
Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458513485653</identifier><identifier>PMID: 23612879</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adolescent ; Adult ; Algorithms ; Antigens - blood ; Autoantibodies - blood ; Biological and medical sciences ; Cerebrospinal fluid. Meninges. Spinal cord ; Child ; Cohort Studies ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Diagnosis, Differential ; Encephalomyelitis, Acute Disseminated - diagnosis ; Encephalomyelitis, Acute Disseminated - immunology ; Female ; Humans ; Immunoglobulin G - blood ; Immunoglobulin M - blood ; Immunomodulators ; Male ; Medical sciences ; Microarray Analysis ; Middle Aged ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Multiple Sclerosis, Relapsing-Remitting - diagnosis ; Multiple Sclerosis, Relapsing-Remitting - immunology ; Myelin Proteins - immunology ; Nervous system (semeiology, syndromes) ; Neurology ; Pharmacology. Drug treatments ; Young Adult</subject><ispartof>Multiple sclerosis, 2013-11, Vol.19 (13), p.1726-1733</ispartof><rights>The Author(s) 2013</rights><rights>2014 INIST-CNRS</rights><rights>SAGE Publications © Nov 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-8eed867f52afe525d0153725918ccfb47e527cffe0915c8f7611e6471865c4d53</citedby><cites>FETCH-LOGICAL-c492t-8eed867f52afe525d0153725918ccfb47e527cffe0915c8f7611e6471865c4d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458513485653$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458513485653$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>230,314,776,780,881,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27918708$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23612879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Haren, Keith</creatorcontrib><creatorcontrib>Tomooka, Beren H</creatorcontrib><creatorcontrib>Kidd, Brian A</creatorcontrib><creatorcontrib>Banwell, Brenda</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Chitnis, Tanuja</creatorcontrib><creatorcontrib>Tenembaum, Silvia N</creatorcontrib><creatorcontrib>Pohl, Daniela</creatorcontrib><creatorcontrib>Rostasy, Kevin</creatorcontrib><creatorcontrib>Dale, Russell C</creatorcontrib><creatorcontrib>O’Connor, Kevin C</creatorcontrib><creatorcontrib>Hafler, David A</creatorcontrib><creatorcontrib>Steinman, Lawrence</creatorcontrib><creatorcontrib>Robinson, William H</creatorcontrib><title>Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>Background and objective:
Acute disseminated encephalomyelitis (ADEM) and relapsing–remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them.
Methods:
We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles.
Results:
ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62–86%; specificity 56–79%) from MS serum (sensitivity 40–87%; specificity 62–86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides.
Conclusions:
Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Algorithms</subject><subject>Antigens - blood</subject><subject>Autoantibodies - blood</subject><subject>Biological and medical sciences</subject><subject>Cerebrospinal fluid. Meninges. Spinal cord</subject><subject>Child</subject><subject>Cohort Studies</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Diagnosis, Differential</subject><subject>Encephalomyelitis, Acute Disseminated - diagnosis</subject><subject>Encephalomyelitis, Acute Disseminated - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin M - blood</subject><subject>Immunomodulators</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microarray Analysis</subject><subject>Middle Aged</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - diagnosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - immunology</subject><subject>Myelin Proteins - immunology</subject><subject>Nervous system (semeiology, syndromes)</subject><subject>Neurology</subject><subject>Pharmacology. Drug treatments</subject><subject>Young Adult</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc9u1DAQxiMEoqVw54QsISQuAU9ix84FCVXlj1SJA3COvM5415VjB9up1Bs3HqBvyJPgsEsplTjZnvl934xnquop0FcAQryGljeMSw4tk7zj7b3qGJgQNe0FvV_uJV2v-aPqUUoXlFIhWv6wOmraDhop-uPqx2eMy0TUkoPy2W7CaDGRHMh0hc56MuOc7VhCo03Z-u1i044ovWRcIwkn61XGkaDXOO-UC7912SZiYphIRKfmVHQ_v1-Xx2TzakKmxWU7OyRJO4wh2fS4emCUS_jkcJ5UX9-dfTn9UJ9_ev_x9O15rVnf5FoijrIThjfKIG_4SIG3ouE9SK3NhokSFNoYpD1wLY3oALBjAmTHNRt5e1K92fvOy2bCUaPPUblhjnZS8WoIyg7_ZrzdDdtwOTAGALItBi8PBjF8WzDlYbJJo3PKY1jSAGXeIFmpX9Dnd9CLsERfvrdSlLbQcFEouqd0GUSKaG6aATqsWx7ubrlInt3-xI3gz1oL8OIAqKSVM1F5bdNfTpR5CSoLV--5pLZ4q7v_Ff4FZ03BcQ</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Van Haren, Keith</creator><creator>Tomooka, Beren H</creator><creator>Kidd, Brian A</creator><creator>Banwell, Brenda</creator><creator>Bar-Or, Amit</creator><creator>Chitnis, Tanuja</creator><creator>Tenembaum, Silvia N</creator><creator>Pohl, Daniela</creator><creator>Rostasy, Kevin</creator><creator>Dale, Russell C</creator><creator>O’Connor, Kevin C</creator><creator>Hafler, David A</creator><creator>Steinman, Lawrence</creator><creator>Robinson, William H</creator><general>SAGE Publications</general><general>Sage Publications</general><general>Sage Publications Ltd</general><scope>IQODW</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>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20131101</creationdate><title>Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis</title><author>Van Haren, Keith ; Tomooka, Beren H ; Kidd, Brian A ; Banwell, Brenda ; Bar-Or, Amit ; Chitnis, Tanuja ; Tenembaum, Silvia N ; Pohl, Daniela ; Rostasy, Kevin ; Dale, Russell C ; O’Connor, Kevin C ; Hafler, David A ; Steinman, Lawrence ; Robinson, William H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-8eed867f52afe525d0153725918ccfb47e527cffe0915c8f7611e6471865c4d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Algorithms</topic><topic>Antigens - blood</topic><topic>Autoantibodies - blood</topic><topic>Biological and medical sciences</topic><topic>Cerebrospinal fluid. Meninges. Spinal cord</topic><topic>Child</topic><topic>Cohort Studies</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Diagnosis, Differential</topic><topic>Encephalomyelitis, Acute Disseminated - diagnosis</topic><topic>Encephalomyelitis, Acute Disseminated - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin M - blood</topic><topic>Immunomodulators</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microarray Analysis</topic><topic>Middle Aged</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - diagnosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - immunology</topic><topic>Myelin Proteins - immunology</topic><topic>Nervous system (semeiology, syndromes)</topic><topic>Neurology</topic><topic>Pharmacology. Drug treatments</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Haren, Keith</creatorcontrib><creatorcontrib>Tomooka, Beren H</creatorcontrib><creatorcontrib>Kidd, Brian A</creatorcontrib><creatorcontrib>Banwell, Brenda</creatorcontrib><creatorcontrib>Bar-Or, Amit</creatorcontrib><creatorcontrib>Chitnis, Tanuja</creatorcontrib><creatorcontrib>Tenembaum, Silvia N</creatorcontrib><creatorcontrib>Pohl, Daniela</creatorcontrib><creatorcontrib>Rostasy, Kevin</creatorcontrib><creatorcontrib>Dale, Russell C</creatorcontrib><creatorcontrib>O’Connor, Kevin C</creatorcontrib><creatorcontrib>Hafler, David A</creatorcontrib><creatorcontrib>Steinman, Lawrence</creatorcontrib><creatorcontrib>Robinson, William H</creatorcontrib><collection>Pascal-Francis</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>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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 China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Haren, Keith</au><au>Tomooka, Beren H</au><au>Kidd, Brian A</au><au>Banwell, Brenda</au><au>Bar-Or, Amit</au><au>Chitnis, Tanuja</au><au>Tenembaum, Silvia N</au><au>Pohl, Daniela</au><au>Rostasy, Kevin</au><au>Dale, Russell C</au><au>O’Connor, Kevin C</au><au>Hafler, David A</au><au>Steinman, Lawrence</au><au>Robinson, William H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>19</volume><issue>13</issue><spage>1726</spage><epage>1733</epage><pages>1726-1733</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><abstract>Background and objective:
Acute disseminated encephalomyelitis (ADEM) and relapsing–remitting multiple sclerosis (RRMS) share overlapping clinical, radiologic and laboratory features at onset. Because autoantibodies may contribute to the pathogenesis of both diseases, we sought to identify autoantibody biomarkers that are capable of distinguishing them.
Methods:
We used custom antigen arrays to profile anti-myelin-peptide autoantibodies in sera derived from individuals with pediatric ADEM (n = 15), pediatric multiple sclerosis (Ped MS; n = 11) and adult MS (n = 15). Using isotype-specific secondary antibodies, we profiled both IgG and IgM reactivities. We used Statistical Analysis of Microarrays software to confirm the differences in autoantibody reactivity profiles between ADEM and MS samples. We used Prediction Analysis of Microarrays software to generate and validate prediction algorithms, based on the autoantibody reactivity profiles.
Results:
ADEM was characterized by IgG autoantibodies targeting epitopes derived from myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein, and alpha-B-crystallin. In contrast, MS was characterized by IgM autoantibodies targeting myelin basic protein, proteolipid protein, myelin-associated oligodendrocyte basic glycoprotein and oligodendrocyte-specific protein. We generated and validated prediction algorithms that distinguish ADEM serum (sensitivity 62–86%; specificity 56–79%) from MS serum (sensitivity 40–87%; specificity 62–86%) on the basis of combined IgG and IgM anti-myelin autoantibody reactivity to a small number of myelin peptides.
Conclusions:
Combined profiles of serum IgG and IgM autoantibodies identified myelin antigens that may be useful for distinguishing MS from ADEM. Further studies are required to establish clinical utility. Further biological assays are required to delineate the pathogenic potential of these antibodies.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>23612879</pmid><doi>10.1177/1352458513485653</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Multiple sclerosis, 2013-11, Vol.19 (13), p.1726-1733 |
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| source | MEDLINE; SAGE Complete |
| subjects | Adolescent Adult Algorithms Antigens - blood Autoantibodies - blood Biological and medical sciences Cerebrospinal fluid. Meninges. Spinal cord Child Cohort Studies Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Diagnosis, Differential Encephalomyelitis, Acute Disseminated - diagnosis Encephalomyelitis, Acute Disseminated - immunology Female Humans Immunoglobulin G - blood Immunoglobulin M - blood Immunomodulators Male Medical sciences Microarray Analysis Middle Aged Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Multiple Sclerosis, Relapsing-Remitting - diagnosis Multiple Sclerosis, Relapsing-Remitting - immunology Myelin Proteins - immunology Nervous system (semeiology, syndromes) Neurology Pharmacology. Drug treatments Young Adult |
| title | Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis |
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