Association between peripheral blood immunological status and intrathecal inflammatory markers differentiate multiple sclerosis clinical phenotypes
Background The difference in the clinical course, response to therapy, and distribution of CNS inflammation in primary-progressive (PPMS) and relapsing-remitting multiple sclerosis (RRMS) suggests differences in the underlying immunological characteristics of the disease. We aimed to investigate dif...
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Veröffentlicht in: | Acta neurologica Belgica 2024-12, Vol.124 (6), p.1935-1944 |
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container_issue | 6 |
container_start_page | 1935 |
container_title | Acta neurologica Belgica |
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creator | Turčić, Ana Knežević, Josip Zaninović, Ljiljana Habek, Mario Skorić, Magdalena Krbot Babić, Antonija Vogrinc, Željka |
description | Background
The difference in the clinical course, response to therapy, and distribution of CNS inflammation in primary-progressive (PPMS) and relapsing-remitting multiple sclerosis (RRMS) suggests differences in the underlying immunological characteristics of the disease. We aimed to investigate differences in immunological profiles in relation to intrathecal inflammation in different MS forms.
Methods
The peripheral blood (PB) proportions of CD4 + and CD8 + T-cells and CD19 + B-cells were retrospectively compared with the markers of intrathecal immunoglobulin G (IgG) synthesis at diagnosis: IgG index, percentage of intrathecal IgG synthesis (IF IgG), the number of oligoclonal bands (OCB), depending on the blood-brain barrier (BBB) function, and antibody specific index to neurotrophic viruses (MRZH reaction).
Results
Thirty-six controls, 71 RRMS and 25 PPMS were enrolled. PPMS had higher percentage of CD4 + T-cells compared to RRMS (
P
= 0.043) and controls (
P
= 0.003). The percentage of CD8 + T-cells and CD19 + B-cells, and respective absolute cell counts did not differ according to the MS phenotype. In RRMS with the dysfunctional BBB, the IgG index (
r
= 0.642,
P
= 0.012) correlated significantly with the CD19 + B-cells while the CD4 + T-cells inversely correlated with IF IgG (
r
=-0.574,
P
= 0.039). Interestingly, in PPMS the number of OCB was positively associated with CD4+ (
r
= 0.603,
P
= 0.015) and negatively associated with CD8 + T-cells (
r
=-0.554,
P
= 0.033), while IF IgG negatively correlated with CD8 + T-cells (
r
=-0.689,
P
= 0.003), but only in the preserved BBB function.
Conclusions
The PB CD4 + T-cells and B-cells were associated with the intrathecal inflammation in RRMS with BBB dysfunction while CD8 + T-cells were involved in PPMS with CNS-compartmentalized inflammation. |
doi_str_mv | 10.1007/s13760-024-02597-8 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3087563100</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3087563100</sourcerecordid><originalsourceid>FETCH-LOGICAL-c228t-f2dcda011b3ba726bcf91a66d0b0048379369276d79d11246f38a8fe5bc096e33</originalsourceid><addsrcrecordid>eNp9Uctu3SAQRVGr5CrND3RRsezGyQDXYJZR1EekSNm0a4TxOCHF4AJWdb-jP1ySm3bZkdBIM2fOcOYQ8p7BJQNQV4UJJaEDvm-v16obTsiO8z10XGvxhuxAAHQaQJ-Ri1KeoMVecqbkKTkTGnTfK7Ejv69LSc7b6lOkI9ZfiJGumP36iNkGOoaUJuqXZYsppAfvWq1UW7dCbWyNWLOtj_hc9nEOdllsTflAF5t_YC508vOMGWNtK5AuW6h-DUiLC5hT8YW64OMLa1sYUz2sWN6Rt7MNBS9e8zn5_vnTt5uv3d39l9ub67vOcT7UbuaTmywwNorRKi5HN2tmpZxgbFIHobSQmis5KT0xxvdyFoMdZuxHB1qiEOfk45F3zennhqWaxReHIdiIaStGwKB6Kdq5G5Qfoa79umSczZp903gwDMyzH-boh2l-mBc_zNCGPrzyb-OC07-Rv9dvAHEElNaKD5jNU9pybJr_R_sHyWKaqA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3087563100</pqid></control><display><type>article</type><title>Association between peripheral blood immunological status and intrathecal inflammatory markers differentiate multiple sclerosis clinical phenotypes</title><source>MEDLINE</source><source>Springer journals</source><creator>Turčić, Ana ; Knežević, Josip ; Zaninović, Ljiljana ; Habek, Mario ; Skorić, Magdalena Krbot ; Babić, Antonija ; Vogrinc, Željka</creator><creatorcontrib>Turčić, Ana ; Knežević, Josip ; Zaninović, Ljiljana ; Habek, Mario ; Skorić, Magdalena Krbot ; Babić, Antonija ; Vogrinc, Željka</creatorcontrib><description>Background
The difference in the clinical course, response to therapy, and distribution of CNS inflammation in primary-progressive (PPMS) and relapsing-remitting multiple sclerosis (RRMS) suggests differences in the underlying immunological characteristics of the disease. We aimed to investigate differences in immunological profiles in relation to intrathecal inflammation in different MS forms.
Methods
The peripheral blood (PB) proportions of CD4 + and CD8 + T-cells and CD19 + B-cells were retrospectively compared with the markers of intrathecal immunoglobulin G (IgG) synthesis at diagnosis: IgG index, percentage of intrathecal IgG synthesis (IF IgG), the number of oligoclonal bands (OCB), depending on the blood-brain barrier (BBB) function, and antibody specific index to neurotrophic viruses (MRZH reaction).
Results
Thirty-six controls, 71 RRMS and 25 PPMS were enrolled. PPMS had higher percentage of CD4 + T-cells compared to RRMS (
P
= 0.043) and controls (
P
= 0.003). The percentage of CD8 + T-cells and CD19 + B-cells, and respective absolute cell counts did not differ according to the MS phenotype. In RRMS with the dysfunctional BBB, the IgG index (
r
= 0.642,
P
= 0.012) correlated significantly with the CD19 + B-cells while the CD4 + T-cells inversely correlated with IF IgG (
r
=-0.574,
P
= 0.039). Interestingly, in PPMS the number of OCB was positively associated with CD4+ (
r
= 0.603,
P
= 0.015) and negatively associated with CD8 + T-cells (
r
=-0.554,
P
= 0.033), while IF IgG negatively correlated with CD8 + T-cells (
r
=-0.689,
P
= 0.003), but only in the preserved BBB function.
Conclusions
The PB CD4 + T-cells and B-cells were associated with the intrathecal inflammation in RRMS with BBB dysfunction while CD8 + T-cells were involved in PPMS with CNS-compartmentalized inflammation.</description><identifier>ISSN: 0300-9009</identifier><identifier>ISSN: 2240-2993</identifier><identifier>EISSN: 2240-2993</identifier><identifier>DOI: 10.1007/s13760-024-02597-8</identifier><identifier>PMID: 39095573</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Adult ; B-Lymphocytes - immunology ; Biomarkers - blood ; Biomedical and Life Sciences ; Biomedicine ; Blood-Brain Barrier ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - immunology ; Female ; Humans ; Immunoglobulin G - blood ; Male ; Medicine/Public Health ; Middle Aged ; Multiple Sclerosis - blood ; Multiple Sclerosis - immunology ; Multiple Sclerosis, Chronic Progressive - blood ; Multiple Sclerosis, Chronic Progressive - immunology ; Multiple Sclerosis, Relapsing-Remitting - blood ; Multiple Sclerosis, Relapsing-Remitting - immunology ; Neurology ; Neuroradiology ; Neurosciences ; Oligoclonal Bands - blood ; Oligoclonal Bands - cerebrospinal fluid ; Original Article ; Phenotype ; Retrospective Studies</subject><ispartof>Acta neurologica Belgica, 2024-12, Vol.124 (6), p.1935-1944</ispartof><rights>The Author(s) under exclusive licence to Belgian Neurological Society 2024 Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s) under exclusive licence to Belgian Neurological Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c228t-f2dcda011b3ba726bcf91a66d0b0048379369276d79d11246f38a8fe5bc096e33</cites><orcidid>0000-0001-8138-4170</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13760-024-02597-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13760-024-02597-8$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39095573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Turčić, Ana</creatorcontrib><creatorcontrib>Knežević, Josip</creatorcontrib><creatorcontrib>Zaninović, Ljiljana</creatorcontrib><creatorcontrib>Habek, Mario</creatorcontrib><creatorcontrib>Skorić, Magdalena Krbot</creatorcontrib><creatorcontrib>Babić, Antonija</creatorcontrib><creatorcontrib>Vogrinc, Željka</creatorcontrib><title>Association between peripheral blood immunological status and intrathecal inflammatory markers differentiate multiple sclerosis clinical phenotypes</title><title>Acta neurologica Belgica</title><addtitle>Acta Neurol Belg</addtitle><addtitle>Acta Neurol Belg</addtitle><description>Background
The difference in the clinical course, response to therapy, and distribution of CNS inflammation in primary-progressive (PPMS) and relapsing-remitting multiple sclerosis (RRMS) suggests differences in the underlying immunological characteristics of the disease. We aimed to investigate differences in immunological profiles in relation to intrathecal inflammation in different MS forms.
Methods
The peripheral blood (PB) proportions of CD4 + and CD8 + T-cells and CD19 + B-cells were retrospectively compared with the markers of intrathecal immunoglobulin G (IgG) synthesis at diagnosis: IgG index, percentage of intrathecal IgG synthesis (IF IgG), the number of oligoclonal bands (OCB), depending on the blood-brain barrier (BBB) function, and antibody specific index to neurotrophic viruses (MRZH reaction).
Results
Thirty-six controls, 71 RRMS and 25 PPMS were enrolled. PPMS had higher percentage of CD4 + T-cells compared to RRMS (
P
= 0.043) and controls (
P
= 0.003). The percentage of CD8 + T-cells and CD19 + B-cells, and respective absolute cell counts did not differ according to the MS phenotype. In RRMS with the dysfunctional BBB, the IgG index (
r
= 0.642,
P
= 0.012) correlated significantly with the CD19 + B-cells while the CD4 + T-cells inversely correlated with IF IgG (
r
=-0.574,
P
= 0.039). Interestingly, in PPMS the number of OCB was positively associated with CD4+ (
r
= 0.603,
P
= 0.015) and negatively associated with CD8 + T-cells (
r
=-0.554,
P
= 0.033), while IF IgG negatively correlated with CD8 + T-cells (
r
=-0.689,
P
= 0.003), but only in the preserved BBB function.
Conclusions
The PB CD4 + T-cells and B-cells were associated with the intrathecal inflammation in RRMS with BBB dysfunction while CD8 + T-cells were involved in PPMS with CNS-compartmentalized inflammation.</description><subject>Adult</subject><subject>B-Lymphocytes - immunology</subject><subject>Biomarkers - blood</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood-Brain Barrier</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin G - blood</subject><subject>Male</subject><subject>Medicine/Public Health</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - blood</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis, Chronic Progressive - blood</subject><subject>Multiple Sclerosis, Chronic Progressive - immunology</subject><subject>Multiple Sclerosis, Relapsing-Remitting - blood</subject><subject>Multiple Sclerosis, Relapsing-Remitting - immunology</subject><subject>Neurology</subject><subject>Neuroradiology</subject><subject>Neurosciences</subject><subject>Oligoclonal Bands - blood</subject><subject>Oligoclonal Bands - cerebrospinal fluid</subject><subject>Original Article</subject><subject>Phenotype</subject><subject>Retrospective Studies</subject><issn>0300-9009</issn><issn>2240-2993</issn><issn>2240-2993</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uctu3SAQRVGr5CrND3RRsezGyQDXYJZR1EekSNm0a4TxOCHF4AJWdb-jP1ySm3bZkdBIM2fOcOYQ8p7BJQNQV4UJJaEDvm-v16obTsiO8z10XGvxhuxAAHQaQJ-Ri1KeoMVecqbkKTkTGnTfK7Ejv69LSc7b6lOkI9ZfiJGumP36iNkGOoaUJuqXZYsppAfvWq1UW7dCbWyNWLOtj_hc9nEOdllsTflAF5t_YC508vOMGWNtK5AuW6h-DUiLC5hT8YW64OMLa1sYUz2sWN6Rt7MNBS9e8zn5_vnTt5uv3d39l9ub67vOcT7UbuaTmywwNorRKi5HN2tmpZxgbFIHobSQmis5KT0xxvdyFoMdZuxHB1qiEOfk45F3zennhqWaxReHIdiIaStGwKB6Kdq5G5Qfoa79umSczZp903gwDMyzH-boh2l-mBc_zNCGPrzyb-OC07-Rv9dvAHEElNaKD5jNU9pybJr_R_sHyWKaqA</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Turčić, Ana</creator><creator>Knežević, Josip</creator><creator>Zaninović, Ljiljana</creator><creator>Habek, Mario</creator><creator>Skorić, Magdalena Krbot</creator><creator>Babić, Antonija</creator><creator>Vogrinc, Željka</creator><general>Springer International Publishing</general><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>7X8</scope><orcidid>https://orcid.org/0000-0001-8138-4170</orcidid></search><sort><creationdate>202412</creationdate><title>Association between peripheral blood immunological status and intrathecal inflammatory markers differentiate multiple sclerosis clinical phenotypes</title><author>Turčić, Ana ; Knežević, Josip ; Zaninović, Ljiljana ; Habek, Mario ; Skorić, Magdalena Krbot ; Babić, Antonija ; Vogrinc, Željka</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c228t-f2dcda011b3ba726bcf91a66d0b0048379369276d79d11246f38a8fe5bc096e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>B-Lymphocytes - immunology</topic><topic>Biomarkers - blood</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blood-Brain Barrier</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin G - blood</topic><topic>Male</topic><topic>Medicine/Public Health</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - blood</topic><topic>Multiple Sclerosis - immunology</topic><topic>Multiple Sclerosis, Chronic Progressive - blood</topic><topic>Multiple Sclerosis, Chronic Progressive - immunology</topic><topic>Multiple Sclerosis, Relapsing-Remitting - blood</topic><topic>Multiple Sclerosis, Relapsing-Remitting - immunology</topic><topic>Neurology</topic><topic>Neuroradiology</topic><topic>Neurosciences</topic><topic>Oligoclonal Bands - blood</topic><topic>Oligoclonal Bands - cerebrospinal fluid</topic><topic>Original Article</topic><topic>Phenotype</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Turčić, Ana</creatorcontrib><creatorcontrib>Knežević, Josip</creatorcontrib><creatorcontrib>Zaninović, Ljiljana</creatorcontrib><creatorcontrib>Habek, Mario</creatorcontrib><creatorcontrib>Skorić, Magdalena Krbot</creatorcontrib><creatorcontrib>Babić, Antonija</creatorcontrib><creatorcontrib>Vogrinc, Željka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Acta neurologica Belgica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Turčić, Ana</au><au>Knežević, Josip</au><au>Zaninović, Ljiljana</au><au>Habek, Mario</au><au>Skorić, Magdalena Krbot</au><au>Babić, Antonija</au><au>Vogrinc, Željka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between peripheral blood immunological status and intrathecal inflammatory markers differentiate multiple sclerosis clinical phenotypes</atitle><jtitle>Acta neurologica Belgica</jtitle><stitle>Acta Neurol Belg</stitle><addtitle>Acta Neurol Belg</addtitle><date>2024-12</date><risdate>2024</risdate><volume>124</volume><issue>6</issue><spage>1935</spage><epage>1944</epage><pages>1935-1944</pages><issn>0300-9009</issn><issn>2240-2993</issn><eissn>2240-2993</eissn><abstract>Background
The difference in the clinical course, response to therapy, and distribution of CNS inflammation in primary-progressive (PPMS) and relapsing-remitting multiple sclerosis (RRMS) suggests differences in the underlying immunological characteristics of the disease. We aimed to investigate differences in immunological profiles in relation to intrathecal inflammation in different MS forms.
Methods
The peripheral blood (PB) proportions of CD4 + and CD8 + T-cells and CD19 + B-cells were retrospectively compared with the markers of intrathecal immunoglobulin G (IgG) synthesis at diagnosis: IgG index, percentage of intrathecal IgG synthesis (IF IgG), the number of oligoclonal bands (OCB), depending on the blood-brain barrier (BBB) function, and antibody specific index to neurotrophic viruses (MRZH reaction).
Results
Thirty-six controls, 71 RRMS and 25 PPMS were enrolled. PPMS had higher percentage of CD4 + T-cells compared to RRMS (
P
= 0.043) and controls (
P
= 0.003). The percentage of CD8 + T-cells and CD19 + B-cells, and respective absolute cell counts did not differ according to the MS phenotype. In RRMS with the dysfunctional BBB, the IgG index (
r
= 0.642,
P
= 0.012) correlated significantly with the CD19 + B-cells while the CD4 + T-cells inversely correlated with IF IgG (
r
=-0.574,
P
= 0.039). Interestingly, in PPMS the number of OCB was positively associated with CD4+ (
r
= 0.603,
P
= 0.015) and negatively associated with CD8 + T-cells (
r
=-0.554,
P
= 0.033), while IF IgG negatively correlated with CD8 + T-cells (
r
=-0.689,
P
= 0.003), but only in the preserved BBB function.
Conclusions
The PB CD4 + T-cells and B-cells were associated with the intrathecal inflammation in RRMS with BBB dysfunction while CD8 + T-cells were involved in PPMS with CNS-compartmentalized inflammation.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>39095573</pmid><doi>10.1007/s13760-024-02597-8</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-8138-4170</orcidid></addata></record> |
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source | MEDLINE; Springer journals |
subjects | Adult B-Lymphocytes - immunology Biomarkers - blood Biomedical and Life Sciences Biomedicine Blood-Brain Barrier CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Female Humans Immunoglobulin G - blood Male Medicine/Public Health Middle Aged Multiple Sclerosis - blood Multiple Sclerosis - immunology Multiple Sclerosis, Chronic Progressive - blood Multiple Sclerosis, Chronic Progressive - immunology Multiple Sclerosis, Relapsing-Remitting - blood Multiple Sclerosis, Relapsing-Remitting - immunology Neurology Neuroradiology Neurosciences Oligoclonal Bands - blood Oligoclonal Bands - cerebrospinal fluid Original Article Phenotype Retrospective Studies |
title | Association between peripheral blood immunological status and intrathecal inflammatory markers differentiate multiple sclerosis clinical phenotypes |
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