The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1
Autoantibodies (AB) against N‐methyl‐D‐aspartate receptor subunit NR1 (NMDAR1) are highly seroprevalent in health and disease. Symptomatic relevance may arise upon compromised blood–brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF...
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| Veröffentlicht in: | Annals of neurology 2016-01, Vol.79 (1), p.144-151 |
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| container_title | Annals of neurology |
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| creator | Castillo-Gomez, Esther Kästner, Anne Steiner, Johann Schneider, Anja Hettling, Bilke Poggi, Giulia Ostehr, Kristin Uhr, Manfred Asif, Abdul R. Matzke, Mike Schmidt, Ulrike Pfander, Viktoria Hammer, Christian Schulz, Thomas F. Binder, Lutz Stöcker, Winfried Weber, Frank Ehrenreich, Hannelore |
| description | Autoantibodies (AB) against N‐methyl‐D‐aspartate receptor subunit NR1 (NMDAR1) are highly seroprevalent in health and disease. Symptomatic relevance may arise upon compromised blood–brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF). Of n = 271 subjects with CSF–serum pairs, 26 were NMDAR1 AB seropositive, but only 1 was CSF positive. Contrariwise, tetanus AB (non–brain‐binding) were present in serum and CSF of all subjects, with CSF levels higher upon BBB dysfunction. Translational mouse experiments proved the hypothesis that the brain acts as an ‘immunoprecipitator’; simultaneous injection of NMDAR1 AB and the non–brain‐binding green fluorescent protein AB resulted in high detectability of the former in brain and the latter in CSF. ANN NEUROL 2016;79:144–151 |
| doi_str_mv | 10.1002/ana.24545 |
| format | Article |
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Symptomatic relevance may arise upon compromised blood–brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF). Of n = 271 subjects with CSF–serum pairs, 26 were NMDAR1 AB seropositive, but only 1 was CSF positive. Contrariwise, tetanus AB (non–brain‐binding) were present in serum and CSF of all subjects, with CSF levels higher upon BBB dysfunction. Translational mouse experiments proved the hypothesis that the brain acts as an ‘immunoprecipitator’; simultaneous injection of NMDAR1 AB and the non–brain‐binding green fluorescent protein AB resulted in high detectability of the former in brain and the latter in CSF. 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Symptomatic relevance may arise upon compromised blood–brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF). Of n = 271 subjects with CSF–serum pairs, 26 were NMDAR1 AB seropositive, but only 1 was CSF positive. Contrariwise, tetanus AB (non–brain‐binding) were present in serum and CSF of all subjects, with CSF levels higher upon BBB dysfunction. Translational mouse experiments proved the hypothesis that the brain acts as an ‘immunoprecipitator’; simultaneous injection of NMDAR1 AB and the non–brain‐binding green fluorescent protein AB resulted in high detectability of the former in brain and the latter in CSF. ANN NEUROL 2016;79:144–151</description><subject>Adult</subject><subject>Animals</subject><subject>Autoantibodies - blood</subject><subject>Autoantibodies - cerebrospinal fluid</subject><subject>Blood-Brain Barrier - physiopathology</subject><subject>Brain - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - blood</subject><subject>Multiple Sclerosis - cerebrospinal fluid</subject><subject>Receptors, N-Methyl-D-Aspartate - immunology</subject><subject>Rodents</subject><subject>Seroepidemiologic Studies</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0U9rFDEYBvAgit1WD34BGfBiD2nzP5PjdtUqtKvoqseQmX3Hps5MxmSC7rc3ddseBMFT4OX3PBAehJ5RckIJYadudCdMSCEfoAWVnOKaCfMQLQhXAkvKxQE6TOmaEGIUJY_RAVOSSMXMAvnNFVRNdH6sXKr8MOQxTBFaP_nZzSFWoasSxDxULs_BjbNvwtZDqty3kklztcaXMF_tevwKuzS5WFJQlQKYbtIpN3n0RX2kT9CjzvUJnt6-R-jzm9eb1Vt88f783Wp5gVvJpMRdS40QrNad6TracmO0oGDKTSnTObFVXFNDKAhoWVfXbQtCO1kzqtyWuIYfoZf73imGHxnSbAefWuh7N0LIyVKtlRJGMfEfVDEuJKtVoS_-otchx7F8pCipa0050UUd71UbQ0oROjtFP7i4s5TYm6lsmcr-marY57eNuRlgey_vtingdA9--h52_26yy_XyrhLvEz7N8Os-4eJ3qzTX0n5dn9vVJ_rlA9lc2jP-G9MGq4A</recordid><startdate>201601</startdate><enddate>201601</enddate><creator>Castillo-Gomez, Esther</creator><creator>Kästner, Anne</creator><creator>Steiner, Johann</creator><creator>Schneider, Anja</creator><creator>Hettling, Bilke</creator><creator>Poggi, Giulia</creator><creator>Ostehr, Kristin</creator><creator>Uhr, Manfred</creator><creator>Asif, Abdul R.</creator><creator>Matzke, Mike</creator><creator>Schmidt, Ulrike</creator><creator>Pfander, Viktoria</creator><creator>Hammer, Christian</creator><creator>Schulz, Thomas F.</creator><creator>Binder, Lutz</creator><creator>Stöcker, Winfried</creator><creator>Weber, Frank</creator><creator>Ehrenreich, Hannelore</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>201601</creationdate><title>The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1</title><author>Castillo-Gomez, Esther ; Kästner, Anne ; Steiner, Johann ; Schneider, Anja ; Hettling, Bilke ; Poggi, Giulia ; Ostehr, Kristin ; Uhr, Manfred ; Asif, Abdul R. ; Matzke, Mike ; Schmidt, Ulrike ; Pfander, Viktoria ; Hammer, Christian ; Schulz, Thomas F. ; Binder, Lutz ; Stöcker, Winfried ; Weber, Frank ; Ehrenreich, Hannelore</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5255-fc1944287f9ff1c399741e9944669fa4d6371901e4ec2f88cce47a58216ad0ab3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Autoantibodies - blood</topic><topic>Autoantibodies - cerebrospinal fluid</topic><topic>Blood-Brain Barrier - physiopathology</topic><topic>Brain - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - blood</topic><topic>Multiple Sclerosis - cerebrospinal fluid</topic><topic>Receptors, N-Methyl-D-Aspartate - immunology</topic><topic>Rodents</topic><topic>Seroepidemiologic Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Castillo-Gomez, Esther</creatorcontrib><creatorcontrib>Kästner, Anne</creatorcontrib><creatorcontrib>Steiner, Johann</creatorcontrib><creatorcontrib>Schneider, Anja</creatorcontrib><creatorcontrib>Hettling, Bilke</creatorcontrib><creatorcontrib>Poggi, Giulia</creatorcontrib><creatorcontrib>Ostehr, Kristin</creatorcontrib><creatorcontrib>Uhr, Manfred</creatorcontrib><creatorcontrib>Asif, Abdul R.</creatorcontrib><creatorcontrib>Matzke, Mike</creatorcontrib><creatorcontrib>Schmidt, Ulrike</creatorcontrib><creatorcontrib>Pfander, Viktoria</creatorcontrib><creatorcontrib>Hammer, Christian</creatorcontrib><creatorcontrib>Schulz, Thomas F.</creatorcontrib><creatorcontrib>Binder, Lutz</creatorcontrib><creatorcontrib>Stöcker, Winfried</creatorcontrib><creatorcontrib>Weber, Frank</creatorcontrib><creatorcontrib>Ehrenreich, Hannelore</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Castillo-Gomez, Esther</au><au>Kästner, Anne</au><au>Steiner, Johann</au><au>Schneider, Anja</au><au>Hettling, Bilke</au><au>Poggi, Giulia</au><au>Ostehr, Kristin</au><au>Uhr, Manfred</au><au>Asif, Abdul R.</au><au>Matzke, Mike</au><au>Schmidt, Ulrike</au><au>Pfander, Viktoria</au><au>Hammer, Christian</au><au>Schulz, Thomas F.</au><au>Binder, Lutz</au><au>Stöcker, Winfried</au><au>Weber, Frank</au><au>Ehrenreich, Hannelore</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2016-01</date><risdate>2016</risdate><volume>79</volume><issue>1</issue><spage>144</spage><epage>151</epage><pages>144-151</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Autoantibodies (AB) against N‐methyl‐D‐aspartate receptor subunit NR1 (NMDAR1) are highly seroprevalent in health and disease. Symptomatic relevance may arise upon compromised blood–brain barrier (BBB). However, it remained unknown whether circulating NMDAR1 AB appear in the cerebrospinal fluid (CSF). Of n = 271 subjects with CSF–serum pairs, 26 were NMDAR1 AB seropositive, but only 1 was CSF positive. Contrariwise, tetanus AB (non–brain‐binding) were present in serum and CSF of all subjects, with CSF levels higher upon BBB dysfunction. Translational mouse experiments proved the hypothesis that the brain acts as an ‘immunoprecipitator’; simultaneous injection of NMDAR1 AB and the non–brain‐binding green fluorescent protein AB resulted in high detectability of the former in brain and the latter in CSF. ANN NEUROL 2016;79:144–151</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>26505629</pmid><doi>10.1002/ana.24545</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Annals of neurology, 2016-01, Vol.79 (1), p.144-151 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Animals Autoantibodies - blood Autoantibodies - cerebrospinal fluid Blood-Brain Barrier - physiopathology Brain - immunology Female Humans Male Mice Mice, Inbred C57BL Middle Aged Multiple Sclerosis - blood Multiple Sclerosis - cerebrospinal fluid Receptors, N-Methyl-D-Aspartate - immunology Rodents Seroepidemiologic Studies |
| title | The brain as immunoprecipitator of serum autoantibodies against N-Methyl-D-aspartate receptor subunit NR1 |
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