Th1 ‐ CD11c+ B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis
Objective Although plasmapheresis is a treatment option for patients with autoimmune neurological diseases, treatment response varies greatly among patients. The main objective of this study was to find out if biological/immune traits correlate with a beneficial response. Methods We thoroughly analy...
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| Veröffentlicht in: | Annals of neurology 2021-10, Vol.90 (4), p.595-611 |
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| container_title | Annals of neurology |
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| creator | Kimura, Kimitoshi Lin, Youwei Yamaguchi, Hiromi Sato, Wakiro Takewaki, Daiki Minote, Misako Doi, Yoshimitsu Okamoto, Tomoko Takahashi, Ryosuke Kondo, Takayuki Yamamura, Takashi |
| description | Objective
Although plasmapheresis is a treatment option for patients with autoimmune neurological diseases, treatment response varies greatly among patients. The main objective of this study was to find out if biological/immune traits correlate with a beneficial response.
Methods
We thoroughly analyzed immune phenotypes in paired blood samples from a cohort of 31 patients with multiple sclerosis before and after plasmapheresis, in parallel with clinical evaluation of treatment response.
Results
The frequency of IFN‐γ+ Th1 cells was persistently higher in those who obtained benefit from plasmapheresis (responders) than nonresponders. The Th1 cell frequency before plasmapheresis provided a high predictive value for beneficial response, achieving area under the curve (AUC) of 0.902. Plasmapheresis treatment decreased inflammation‐related gene expressions in Th1 cells. Meanwhile, IFNG expression in Th1 cells positively correlated with the frequency of CD11c+ B cells, of which a pathogenic role has been suggested in several autoimmune diseases. In line with this, in vitro experiments showed that CD11c+ B cells would increase in response to exogenous IFN‐γ compared to IL‐4, and secrete high amounts of IgG. B cell receptor analysis indicated that clonal expansion of CD11c+ B cells takes place in patients with multiple sclerosis. Interestingly, CD11c+ B cells, which showed unique gene expression profile, decreased after plasmapheresis treatment along with all the immunoglobulin subsets in the circulation.
Interpretation
Taken together, we postulate that Th1 cell ‐ CD11c+ B cell axis is involved in treatment response to plasmapheresis, giving us clues to better understanding of complicated pathogenesis of autoimmune diseases, and getting closer to a personalized therapy. ANN NEUROL 2021;90:595–611 |
| doi_str_mv | 10.1002/ana.26202 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9293420</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2563704201</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4432-f6a39e605ff64c72cc814a6883581833bb039f556db2e3183a23aa29053e03213</originalsourceid><addsrcrecordid>eNp1kd9OFDEUhxujkRW94AVIE28wZqDtabszNyTjKmKCShCvvGi63TNuSXc6TGdE7ngEn9EnobhIwMSrJqdfvvPnR8gWZ7ucMbFnW7srtGDiEZlwBbwohawekwkDLQvFQW6QZymdMcYqzdlTsgFSCqn0dEK-nS45_X31i87ecu5e0zd0hiHQ-qdPtE4pOm8HXNALPyzpCaYutgnpEOlxsGlluyX2mDLqW_pxDIPvAtIvLmAfc_U5edLYkPDF7btJvh68O50dFkef33-Y1UeFkxJE0WgLFWqmmkZLNxXOlVxaXZagSl4CzOcMqkYpvZgLhFyxAqwVFVOADASHTbK_9nbjfIULh-3Q22C63q9sf2mi9ebhT-uX5nv8YSpRgRQsC3ZuBX08HzENZuWTy3ewLcYxGaE0TFkmb3q9_Ac9i2Pf5vUyNdW6hEqLTL1aUy4fIvXY3A3DmbmJzOTIzJ_IMrt9f_o78m9GGdhbAxc-4OX_Tab-VK-V14jJnmg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2576683962</pqid></control><display><type>article</type><title>Th1 ‐ CD11c+ B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Kimura, Kimitoshi ; Lin, Youwei ; Yamaguchi, Hiromi ; Sato, Wakiro ; Takewaki, Daiki ; Minote, Misako ; Doi, Yoshimitsu ; Okamoto, Tomoko ; Takahashi, Ryosuke ; Kondo, Takayuki ; Yamamura, Takashi</creator><creatorcontrib>Kimura, Kimitoshi ; Lin, Youwei ; Yamaguchi, Hiromi ; Sato, Wakiro ; Takewaki, Daiki ; Minote, Misako ; Doi, Yoshimitsu ; Okamoto, Tomoko ; Takahashi, Ryosuke ; Kondo, Takayuki ; Yamamura, Takashi</creatorcontrib><description>Objective
Although plasmapheresis is a treatment option for patients with autoimmune neurological diseases, treatment response varies greatly among patients. The main objective of this study was to find out if biological/immune traits correlate with a beneficial response.
Methods
We thoroughly analyzed immune phenotypes in paired blood samples from a cohort of 31 patients with multiple sclerosis before and after plasmapheresis, in parallel with clinical evaluation of treatment response.
Results
The frequency of IFN‐γ+ Th1 cells was persistently higher in those who obtained benefit from plasmapheresis (responders) than nonresponders. The Th1 cell frequency before plasmapheresis provided a high predictive value for beneficial response, achieving area under the curve (AUC) of 0.902. Plasmapheresis treatment decreased inflammation‐related gene expressions in Th1 cells. Meanwhile, IFNG expression in Th1 cells positively correlated with the frequency of CD11c+ B cells, of which a pathogenic role has been suggested in several autoimmune diseases. In line with this, in vitro experiments showed that CD11c+ B cells would increase in response to exogenous IFN‐γ compared to IL‐4, and secrete high amounts of IgG. B cell receptor analysis indicated that clonal expansion of CD11c+ B cells takes place in patients with multiple sclerosis. Interestingly, CD11c+ B cells, which showed unique gene expression profile, decreased after plasmapheresis treatment along with all the immunoglobulin subsets in the circulation.
Interpretation
Taken together, we postulate that Th1 cell ‐ CD11c+ B cell axis is involved in treatment response to plasmapheresis, giving us clues to better understanding of complicated pathogenesis of autoimmune diseases, and getting closer to a personalized therapy. ANN NEUROL 2021;90:595–611</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.26202</identifier><identifier>PMID: 34424567</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adult ; Apheresis ; Autoimmune diseases ; Autoimmune Diseases - immunology ; B-Lymphocytes - immunology ; CD11c antigen ; Cytokines - metabolism ; Dendritic Cells - immunology ; Gene expression ; Health services ; Humans ; Immunoglobulin G ; Interferon ; Lymphocytes B ; Lymphocytes T ; Male ; Middle Aged ; Multiple sclerosis ; Multiple Sclerosis - immunology ; Multiple Sclerosis - metabolism ; Neurological diseases ; Pathogenesis ; Patients ; Phenotypes ; Plasmapheresis ; Plasmapheresis - methods ; Th1 Cells - immunology ; Th1 Cells - metabolism</subject><ispartof>Annals of neurology, 2021-10, Vol.90 (4), p.595-611</ispartof><rights>2021 The Authors. published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc/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-c4432-f6a39e605ff64c72cc814a6883581833bb039f556db2e3183a23aa29053e03213</citedby><cites>FETCH-LOGICAL-c4432-f6a39e605ff64c72cc814a6883581833bb039f556db2e3183a23aa29053e03213</cites><orcidid>0000-0002-8359-2886</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.26202$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.26202$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34424567$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kimura, Kimitoshi</creatorcontrib><creatorcontrib>Lin, Youwei</creatorcontrib><creatorcontrib>Yamaguchi, Hiromi</creatorcontrib><creatorcontrib>Sato, Wakiro</creatorcontrib><creatorcontrib>Takewaki, Daiki</creatorcontrib><creatorcontrib>Minote, Misako</creatorcontrib><creatorcontrib>Doi, Yoshimitsu</creatorcontrib><creatorcontrib>Okamoto, Tomoko</creatorcontrib><creatorcontrib>Takahashi, Ryosuke</creatorcontrib><creatorcontrib>Kondo, Takayuki</creatorcontrib><creatorcontrib>Yamamura, Takashi</creatorcontrib><title>Th1 ‐ CD11c+ B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
Although plasmapheresis is a treatment option for patients with autoimmune neurological diseases, treatment response varies greatly among patients. The main objective of this study was to find out if biological/immune traits correlate with a beneficial response.
Methods
We thoroughly analyzed immune phenotypes in paired blood samples from a cohort of 31 patients with multiple sclerosis before and after plasmapheresis, in parallel with clinical evaluation of treatment response.
Results
The frequency of IFN‐γ+ Th1 cells was persistently higher in those who obtained benefit from plasmapheresis (responders) than nonresponders. The Th1 cell frequency before plasmapheresis provided a high predictive value for beneficial response, achieving area under the curve (AUC) of 0.902. Plasmapheresis treatment decreased inflammation‐related gene expressions in Th1 cells. Meanwhile, IFNG expression in Th1 cells positively correlated with the frequency of CD11c+ B cells, of which a pathogenic role has been suggested in several autoimmune diseases. In line with this, in vitro experiments showed that CD11c+ B cells would increase in response to exogenous IFN‐γ compared to IL‐4, and secrete high amounts of IgG. B cell receptor analysis indicated that clonal expansion of CD11c+ B cells takes place in patients with multiple sclerosis. Interestingly, CD11c+ B cells, which showed unique gene expression profile, decreased after plasmapheresis treatment along with all the immunoglobulin subsets in the circulation.
Interpretation
Taken together, we postulate that Th1 cell ‐ CD11c+ B cell axis is involved in treatment response to plasmapheresis, giving us clues to better understanding of complicated pathogenesis of autoimmune diseases, and getting closer to a personalized therapy. ANN NEUROL 2021;90:595–611</description><subject>Adult</subject><subject>Apheresis</subject><subject>Autoimmune diseases</subject><subject>Autoimmune Diseases - immunology</subject><subject>B-Lymphocytes - immunology</subject><subject>CD11c antigen</subject><subject>Cytokines - metabolism</subject><subject>Dendritic Cells - immunology</subject><subject>Gene expression</subject><subject>Health services</subject><subject>Humans</subject><subject>Immunoglobulin G</subject><subject>Interferon</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis - metabolism</subject><subject>Neurological diseases</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Plasmapheresis</subject><subject>Plasmapheresis - methods</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kd9OFDEUhxujkRW94AVIE28wZqDtabszNyTjKmKCShCvvGi63TNuSXc6TGdE7ngEn9EnobhIwMSrJqdfvvPnR8gWZ7ucMbFnW7srtGDiEZlwBbwohawekwkDLQvFQW6QZymdMcYqzdlTsgFSCqn0dEK-nS45_X31i87ecu5e0zd0hiHQ-qdPtE4pOm8HXNALPyzpCaYutgnpEOlxsGlluyX2mDLqW_pxDIPvAtIvLmAfc_U5edLYkPDF7btJvh68O50dFkef33-Y1UeFkxJE0WgLFWqmmkZLNxXOlVxaXZagSl4CzOcMqkYpvZgLhFyxAqwVFVOADASHTbK_9nbjfIULh-3Q22C63q9sf2mi9ebhT-uX5nv8YSpRgRQsC3ZuBX08HzENZuWTy3ewLcYxGaE0TFkmb3q9_Ac9i2Pf5vUyNdW6hEqLTL1aUy4fIvXY3A3DmbmJzOTIzJ_IMrt9f_o78m9GGdhbAxc-4OX_Tab-VK-V14jJnmg</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Kimura, Kimitoshi</creator><creator>Lin, Youwei</creator><creator>Yamaguchi, Hiromi</creator><creator>Sato, Wakiro</creator><creator>Takewaki, Daiki</creator><creator>Minote, Misako</creator><creator>Doi, Yoshimitsu</creator><creator>Okamoto, Tomoko</creator><creator>Takahashi, Ryosuke</creator><creator>Kondo, Takayuki</creator><creator>Yamamura, Takashi</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</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>5PM</scope><orcidid>https://orcid.org/0000-0002-8359-2886</orcidid></search><sort><creationdate>202110</creationdate><title>Th1 ‐ CD11c+ B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis</title><author>Kimura, Kimitoshi ; Lin, Youwei ; Yamaguchi, Hiromi ; Sato, Wakiro ; Takewaki, Daiki ; Minote, Misako ; Doi, Yoshimitsu ; Okamoto, Tomoko ; Takahashi, Ryosuke ; Kondo, Takayuki ; Yamamura, Takashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4432-f6a39e605ff64c72cc814a6883581833bb039f556db2e3183a23aa29053e03213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Apheresis</topic><topic>Autoimmune diseases</topic><topic>Autoimmune Diseases - immunology</topic><topic>B-Lymphocytes - immunology</topic><topic>CD11c antigen</topic><topic>Cytokines - metabolism</topic><topic>Dendritic Cells - immunology</topic><topic>Gene expression</topic><topic>Health services</topic><topic>Humans</topic><topic>Immunoglobulin G</topic><topic>Interferon</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis - immunology</topic><topic>Multiple Sclerosis - metabolism</topic><topic>Neurological diseases</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Plasmapheresis</topic><topic>Plasmapheresis - methods</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kimura, Kimitoshi</creatorcontrib><creatorcontrib>Lin, Youwei</creatorcontrib><creatorcontrib>Yamaguchi, Hiromi</creatorcontrib><creatorcontrib>Sato, Wakiro</creatorcontrib><creatorcontrib>Takewaki, Daiki</creatorcontrib><creatorcontrib>Minote, Misako</creatorcontrib><creatorcontrib>Doi, Yoshimitsu</creatorcontrib><creatorcontrib>Okamoto, Tomoko</creatorcontrib><creatorcontrib>Takahashi, Ryosuke</creatorcontrib><creatorcontrib>Kondo, Takayuki</creatorcontrib><creatorcontrib>Yamamura, Takashi</creatorcontrib><collection>Wiley Online Library Open Access</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>PubMed Central (Full Participant titles)</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kimura, Kimitoshi</au><au>Lin, Youwei</au><au>Yamaguchi, Hiromi</au><au>Sato, Wakiro</au><au>Takewaki, Daiki</au><au>Minote, Misako</au><au>Doi, Yoshimitsu</au><au>Okamoto, Tomoko</au><au>Takahashi, Ryosuke</au><au>Kondo, Takayuki</au><au>Yamamura, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Th1 ‐ CD11c+ B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2021-10</date><risdate>2021</risdate><volume>90</volume><issue>4</issue><spage>595</spage><epage>611</epage><pages>595-611</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Objective
Although plasmapheresis is a treatment option for patients with autoimmune neurological diseases, treatment response varies greatly among patients. The main objective of this study was to find out if biological/immune traits correlate with a beneficial response.
Methods
We thoroughly analyzed immune phenotypes in paired blood samples from a cohort of 31 patients with multiple sclerosis before and after plasmapheresis, in parallel with clinical evaluation of treatment response.
Results
The frequency of IFN‐γ+ Th1 cells was persistently higher in those who obtained benefit from plasmapheresis (responders) than nonresponders. The Th1 cell frequency before plasmapheresis provided a high predictive value for beneficial response, achieving area under the curve (AUC) of 0.902. Plasmapheresis treatment decreased inflammation‐related gene expressions in Th1 cells. Meanwhile, IFNG expression in Th1 cells positively correlated with the frequency of CD11c+ B cells, of which a pathogenic role has been suggested in several autoimmune diseases. In line with this, in vitro experiments showed that CD11c+ B cells would increase in response to exogenous IFN‐γ compared to IL‐4, and secrete high amounts of IgG. B cell receptor analysis indicated that clonal expansion of CD11c+ B cells takes place in patients with multiple sclerosis. Interestingly, CD11c+ B cells, which showed unique gene expression profile, decreased after plasmapheresis treatment along with all the immunoglobulin subsets in the circulation.
Interpretation
Taken together, we postulate that Th1 cell ‐ CD11c+ B cell axis is involved in treatment response to plasmapheresis, giving us clues to better understanding of complicated pathogenesis of autoimmune diseases, and getting closer to a personalized therapy. ANN NEUROL 2021;90:595–611</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>34424567</pmid><doi>10.1002/ana.26202</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-8359-2886</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Apheresis Autoimmune diseases Autoimmune Diseases - immunology B-Lymphocytes - immunology CD11c antigen Cytokines - metabolism Dendritic Cells - immunology Gene expression Health services Humans Immunoglobulin G Interferon Lymphocytes B Lymphocytes T Male Middle Aged Multiple sclerosis Multiple Sclerosis - immunology Multiple Sclerosis - metabolism Neurological diseases Pathogenesis Patients Phenotypes Plasmapheresis Plasmapheresis - methods Th1 Cells - immunology Th1 Cells - metabolism |
| title | Th1 ‐ CD11c+ B Cell Axis Associated with Response to Plasmapheresis in Multiple Sclerosis |
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