T-cell response against varicella-zoster virus in fingolimod-treated MS patients
OBJECTIVE:To study the immune response against varicella-zoster virus (VZV) in patients with multiple sclerosis before and during fingolimod therapy. METHODS:The VZV-specific immune response was studied using interferon (IFN)-γ enzyme-linked immunosorbent spot assay, proliferation assays, and upregu...
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| Veröffentlicht in: | Neurology 2013-07, Vol.81 (2), p.174-181 |
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| creator | Ricklin, Meret E Lorscheider, Johannes Waschbisch, Anne Paroz, Cecile Mehta, Satish K Pierson, Duane L Kuhle, Jens Fischer-Barnicol, Bettina Sprenger, Till Lindberg, Raija L.P Kappos, Ludwig Derfuss, Tobias |
| description | OBJECTIVE:To study the immune response against varicella-zoster virus (VZV) in patients with multiple sclerosis before and during fingolimod therapy.
METHODS:The VZV-specific immune response was studied using interferon (IFN)-γ enzyme-linked immunosorbent spot assay, proliferation assays, and upregulation of T-cell activation markers in patients before (n = 38) and after 3 months of fingolimod therapy (n = 34), in untreated (n = 33) and IFN-β–treated (n = 25) patients with multiple sclerosis, and in healthy controls (n = 22). Viral replication was analyzed by using real-time PCR in 76 peripheral blood mononuclear cell samples and 146 saliva samples.
RESULTS:Treatment with fingolimod led to a marked reduction of CD3 T cells with a relative decrease of naive and central memory T cells and an increase of effector memory T cells. Expression of the activation markers CD137 and CD69 upon VZV stimulation was unaltered by fingolimod. However, the absolute number of cells proliferating upon VZV stimulation was reduced in the blood of patients treated with fingolimod. Also, VZV-specific and Epstein-Barr virus (EBV)-specific IFN-γ–producing cells were reduced after fingolimod therapy. Seven of the 35 patients treated with fingolimod showed signs of VZV or EBV reactivation in saliva compared with 3 of the 111 controls. None of the 76 tested samples showed signs of viral reactivation in the peripheral blood mononuclear cells.
CONCLUSION:Patients treated with fingolimod show a slightly reduced antiviral T-cell response. This reduced response is accompanied by a subclinical reactivation of VZV or EBV in the saliva of 20% of patients treated with fingolimod. |
| doi_str_mv | 10.1212/WNL.0b013e31829a3311 |
| format | Article |
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METHODS:The VZV-specific immune response was studied using interferon (IFN)-γ enzyme-linked immunosorbent spot assay, proliferation assays, and upregulation of T-cell activation markers in patients before (n = 38) and after 3 months of fingolimod therapy (n = 34), in untreated (n = 33) and IFN-β–treated (n = 25) patients with multiple sclerosis, and in healthy controls (n = 22). Viral replication was analyzed by using real-time PCR in 76 peripheral blood mononuclear cell samples and 146 saliva samples.
RESULTS:Treatment with fingolimod led to a marked reduction of CD3 T cells with a relative decrease of naive and central memory T cells and an increase of effector memory T cells. Expression of the activation markers CD137 and CD69 upon VZV stimulation was unaltered by fingolimod. However, the absolute number of cells proliferating upon VZV stimulation was reduced in the blood of patients treated with fingolimod. Also, VZV-specific and Epstein-Barr virus (EBV)-specific IFN-γ–producing cells were reduced after fingolimod therapy. Seven of the 35 patients treated with fingolimod showed signs of VZV or EBV reactivation in saliva compared with 3 of the 111 controls. None of the 76 tested samples showed signs of viral reactivation in the peripheral blood mononuclear cells.
CONCLUSION:Patients treated with fingolimod show a slightly reduced antiviral T-cell response. This reduced response is accompanied by a subclinical reactivation of VZV or EBV in the saliva of 20% of patients treated with fingolimod.</description><identifier>ISSN: 0028-3878</identifier><identifier>EISSN: 1526-632X</identifier><identifier>DOI: 10.1212/WNL.0b013e31829a3311</identifier><identifier>PMID: 23700335</identifier><identifier>CODEN: NEURAI</identifier><language>eng</language><publisher>Hagerstown, MD: American Academy of Neurology</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Drug Administration Schedule ; Epstein-Barr virus ; Female ; Fingolimod Hydrochloride ; Herpes Zoster - immunology ; Herpes Zoster - pathology ; Herpes Zoster - virology ; Herpesvirus 3, Human - drug effects ; Herpesvirus 3, Human - immunology ; Herpesvirus 4, Human - immunology ; Human viral diseases ; Humans ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - adverse effects ; Immunosuppressive Agents - pharmacology ; Infectious diseases ; Interferon-beta - therapeutic use ; Male ; Medical sciences ; Middle Aged ; Multiple Sclerosis - drug therapy ; Multiple Sclerosis - immunology ; Multiple Sclerosis - virology ; Neurology ; Propylene Glycols - administration & dosage ; Propylene Glycols - adverse effects ; Propylene Glycols - therapeutic use ; Saliva - virology ; Sphingosine - administration & dosage ; Sphingosine - adverse effects ; Sphingosine - analogs & derivatives ; Sphingosine - therapeutic use ; T-Lymphocytes - drug effects ; T-Lymphocytes - immunology ; T-Lymphocytes - virology ; Varicella-zoster virus ; Viral diseases ; Viral diseases of the nervous system ; Virus Activation - drug effects ; Virus Activation - immunology</subject><ispartof>Neurology, 2013-07, Vol.81 (2), p.174-181</ispartof><rights>2013 American Academy of Neurology</rights><rights>2014 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4153-dadd9c87bf4462e62fee37943b623b3ce815911bee6c2108c619a89ba243f08f3</citedby><cites>FETCH-LOGICAL-c4153-dadd9c87bf4462e62fee37943b623b3ce815911bee6c2108c619a89ba243f08f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27517740$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23700335$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ricklin, Meret E</creatorcontrib><creatorcontrib>Lorscheider, Johannes</creatorcontrib><creatorcontrib>Waschbisch, Anne</creatorcontrib><creatorcontrib>Paroz, Cecile</creatorcontrib><creatorcontrib>Mehta, Satish K</creatorcontrib><creatorcontrib>Pierson, Duane L</creatorcontrib><creatorcontrib>Kuhle, Jens</creatorcontrib><creatorcontrib>Fischer-Barnicol, Bettina</creatorcontrib><creatorcontrib>Sprenger, Till</creatorcontrib><creatorcontrib>Lindberg, Raija L.P</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Derfuss, Tobias</creatorcontrib><title>T-cell response against varicella-zoster virus in fingolimod-treated MS patients</title><title>Neurology</title><addtitle>Neurology</addtitle><description>OBJECTIVE:To study the immune response against varicella-zoster virus (VZV) in patients with multiple sclerosis before and during fingolimod therapy.
METHODS:The VZV-specific immune response was studied using interferon (IFN)-γ enzyme-linked immunosorbent spot assay, proliferation assays, and upregulation of T-cell activation markers in patients before (n = 38) and after 3 months of fingolimod therapy (n = 34), in untreated (n = 33) and IFN-β–treated (n = 25) patients with multiple sclerosis, and in healthy controls (n = 22). Viral replication was analyzed by using real-time PCR in 76 peripheral blood mononuclear cell samples and 146 saliva samples.
RESULTS:Treatment with fingolimod led to a marked reduction of CD3 T cells with a relative decrease of naive and central memory T cells and an increase of effector memory T cells. Expression of the activation markers CD137 and CD69 upon VZV stimulation was unaltered by fingolimod. However, the absolute number of cells proliferating upon VZV stimulation was reduced in the blood of patients treated with fingolimod. Also, VZV-specific and Epstein-Barr virus (EBV)-specific IFN-γ–producing cells were reduced after fingolimod therapy. Seven of the 35 patients treated with fingolimod showed signs of VZV or EBV reactivation in saliva compared with 3 of the 111 controls. None of the 76 tested samples showed signs of viral reactivation in the peripheral blood mononuclear cells.
CONCLUSION:Patients treated with fingolimod show a slightly reduced antiviral T-cell response. This reduced response is accompanied by a subclinical reactivation of VZV or EBV in the saliva of 20% of patients treated with fingolimod.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Drug Administration Schedule</subject><subject>Epstein-Barr virus</subject><subject>Female</subject><subject>Fingolimod Hydrochloride</subject><subject>Herpes Zoster - immunology</subject><subject>Herpes Zoster - pathology</subject><subject>Herpes Zoster - virology</subject><subject>Herpesvirus 3, Human - drug effects</subject><subject>Herpesvirus 3, Human - immunology</subject><subject>Herpesvirus 4, Human - immunology</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Infectious diseases</subject><subject>Interferon-beta - therapeutic use</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - drug therapy</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis - virology</subject><subject>Neurology</subject><subject>Propylene Glycols - administration & dosage</subject><subject>Propylene Glycols - adverse effects</subject><subject>Propylene Glycols - therapeutic use</subject><subject>Saliva - virology</subject><subject>Sphingosine - administration & dosage</subject><subject>Sphingosine - adverse effects</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - therapeutic use</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - virology</subject><subject>Varicella-zoster virus</subject><subject>Viral diseases</subject><subject>Viral diseases of the nervous system</subject><subject>Virus Activation - drug effects</subject><subject>Virus Activation - immunology</subject><issn>0028-3878</issn><issn>1526-632X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi1ERZfCP0AoFyQuLh6P448jqoAiLbQSRXCLHGfSGrLJ1k5alV-PS5cP9YIvI3memXf0MPYMxCFIkK--fFwfilYAEoKVziMCPGArqKXmGuXXh2wlhLQcrbH77HHO34QoTeMesX2JRgjEesVOz3igYagS5e00Zqr8uY9jnqsrn-Jtx_MfU54pVVcxLbmKY9XH8Xwa4mbq-JzIz9RVHz5VWz9HGuf8hO31fsj0dFcP2Oe3b86Ojvn65N37o9drHhTUyDvfdS5Y0_ZKaUla9kRonMJWS2wxkIXaAbREOkgQNmhw3rrWS4W9sD0esJd3e7dpulwoz80m5l8HjzQtuYFaGaux1vb_KDonda1BFFTdoSFNOSfqm22KG59uGhDNrfamaG_uay9jz3cJS7uh7s_Qb88FeLEDfA5-6JMfQ8x_OVODMeqf_OtpKNLz92G5ptRckB_mi0aUpwEUlyVfGOEELz-A-BMN3JrC</recordid><startdate>20130709</startdate><enddate>20130709</enddate><creator>Ricklin, Meret E</creator><creator>Lorscheider, Johannes</creator><creator>Waschbisch, Anne</creator><creator>Paroz, Cecile</creator><creator>Mehta, Satish K</creator><creator>Pierson, Duane L</creator><creator>Kuhle, Jens</creator><creator>Fischer-Barnicol, Bettina</creator><creator>Sprenger, Till</creator><creator>Lindberg, Raija L.P</creator><creator>Kappos, Ludwig</creator><creator>Derfuss, Tobias</creator><general>American Academy of Neurology</general><general>Lippincott Williams & Wilkins</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>7X8</scope><scope>7TK</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>20130709</creationdate><title>T-cell response against varicella-zoster virus in fingolimod-treated MS patients</title><author>Ricklin, Meret E ; Lorscheider, Johannes ; Waschbisch, Anne ; Paroz, Cecile ; Mehta, Satish K ; Pierson, Duane L ; Kuhle, Jens ; Fischer-Barnicol, Bettina ; Sprenger, Till ; Lindberg, Raija L.P ; Kappos, Ludwig ; Derfuss, Tobias</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4153-dadd9c87bf4462e62fee37943b623b3ce815911bee6c2108c619a89ba243f08f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Drug Administration Schedule</topic><topic>Epstein-Barr virus</topic><topic>Female</topic><topic>Fingolimod Hydrochloride</topic><topic>Herpes Zoster - immunology</topic><topic>Herpes Zoster - pathology</topic><topic>Herpes Zoster - virology</topic><topic>Herpesvirus 3, Human - drug effects</topic><topic>Herpesvirus 3, Human - immunology</topic><topic>Herpesvirus 4, Human - immunology</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Infectious diseases</topic><topic>Interferon-beta - therapeutic use</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - drug therapy</topic><topic>Multiple Sclerosis - immunology</topic><topic>Multiple Sclerosis - virology</topic><topic>Neurology</topic><topic>Propylene Glycols - administration & dosage</topic><topic>Propylene Glycols - adverse effects</topic><topic>Propylene Glycols - therapeutic use</topic><topic>Saliva - virology</topic><topic>Sphingosine - administration & dosage</topic><topic>Sphingosine - adverse effects</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Sphingosine - therapeutic use</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - virology</topic><topic>Varicella-zoster virus</topic><topic>Viral diseases</topic><topic>Viral diseases of the nervous system</topic><topic>Virus Activation - drug effects</topic><topic>Virus Activation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ricklin, Meret E</creatorcontrib><creatorcontrib>Lorscheider, Johannes</creatorcontrib><creatorcontrib>Waschbisch, Anne</creatorcontrib><creatorcontrib>Paroz, Cecile</creatorcontrib><creatorcontrib>Mehta, Satish K</creatorcontrib><creatorcontrib>Pierson, Duane L</creatorcontrib><creatorcontrib>Kuhle, Jens</creatorcontrib><creatorcontrib>Fischer-Barnicol, Bettina</creatorcontrib><creatorcontrib>Sprenger, Till</creatorcontrib><creatorcontrib>Lindberg, Raija L.P</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Derfuss, Tobias</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>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ricklin, Meret E</au><au>Lorscheider, Johannes</au><au>Waschbisch, Anne</au><au>Paroz, Cecile</au><au>Mehta, Satish K</au><au>Pierson, Duane L</au><au>Kuhle, Jens</au><au>Fischer-Barnicol, Bettina</au><au>Sprenger, Till</au><au>Lindberg, Raija L.P</au><au>Kappos, Ludwig</au><au>Derfuss, Tobias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>T-cell response against varicella-zoster virus in fingolimod-treated MS patients</atitle><jtitle>Neurology</jtitle><addtitle>Neurology</addtitle><date>2013-07-09</date><risdate>2013</risdate><volume>81</volume><issue>2</issue><spage>174</spage><epage>181</epage><pages>174-181</pages><issn>0028-3878</issn><eissn>1526-632X</eissn><coden>NEURAI</coden><abstract>OBJECTIVE:To study the immune response against varicella-zoster virus (VZV) in patients with multiple sclerosis before and during fingolimod therapy.
METHODS:The VZV-specific immune response was studied using interferon (IFN)-γ enzyme-linked immunosorbent spot assay, proliferation assays, and upregulation of T-cell activation markers in patients before (n = 38) and after 3 months of fingolimod therapy (n = 34), in untreated (n = 33) and IFN-β–treated (n = 25) patients with multiple sclerosis, and in healthy controls (n = 22). Viral replication was analyzed by using real-time PCR in 76 peripheral blood mononuclear cell samples and 146 saliva samples.
RESULTS:Treatment with fingolimod led to a marked reduction of CD3 T cells with a relative decrease of naive and central memory T cells and an increase of effector memory T cells. Expression of the activation markers CD137 and CD69 upon VZV stimulation was unaltered by fingolimod. However, the absolute number of cells proliferating upon VZV stimulation was reduced in the blood of patients treated with fingolimod. Also, VZV-specific and Epstein-Barr virus (EBV)-specific IFN-γ–producing cells were reduced after fingolimod therapy. Seven of the 35 patients treated with fingolimod showed signs of VZV or EBV reactivation in saliva compared with 3 of the 111 controls. None of the 76 tested samples showed signs of viral reactivation in the peripheral blood mononuclear cells.
CONCLUSION:Patients treated with fingolimod show a slightly reduced antiviral T-cell response. This reduced response is accompanied by a subclinical reactivation of VZV or EBV in the saliva of 20% of patients treated with fingolimod.</abstract><cop>Hagerstown, MD</cop><pub>American Academy of Neurology</pub><pmid>23700335</pmid><doi>10.1212/WNL.0b013e31829a3311</doi><tpages>8</tpages></addata></record> |
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| ispartof | Neurology, 2013-07, Vol.81 (2), p.174-181 |
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| subjects | Adult Aged Biological and medical sciences Drug Administration Schedule Epstein-Barr virus Female Fingolimod Hydrochloride Herpes Zoster - immunology Herpes Zoster - pathology Herpes Zoster - virology Herpesvirus 3, Human - drug effects Herpesvirus 3, Human - immunology Herpesvirus 4, Human - immunology Human viral diseases Humans Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - adverse effects Immunosuppressive Agents - pharmacology Infectious diseases Interferon-beta - therapeutic use Male Medical sciences Middle Aged Multiple Sclerosis - drug therapy Multiple Sclerosis - immunology Multiple Sclerosis - virology Neurology Propylene Glycols - administration & dosage Propylene Glycols - adverse effects Propylene Glycols - therapeutic use Saliva - virology Sphingosine - administration & dosage Sphingosine - adverse effects Sphingosine - analogs & derivatives Sphingosine - therapeutic use T-Lymphocytes - drug effects T-Lymphocytes - immunology T-Lymphocytes - virology Varicella-zoster virus Viral diseases Viral diseases of the nervous system Virus Activation - drug effects Virus Activation - immunology |
| title | T-cell response against varicella-zoster virus in fingolimod-treated MS patients |
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