Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients
Backgrounds Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection. Aims This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment. Methods CHC patients ( n = 20) who received DAA treatment, cl...
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| Veröffentlicht in: | Digestive diseases and sciences 2020-05, Vol.65 (5), p.1385-1395 |
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| creator | Wu, Shu-Fen Tseng, Chih-Wei Ho, Yun-Che Chen, Yen-Chun Ko, Ping-Hung He, Yi-Ting Tseng, Kuo-Chih |
| description | Backgrounds
Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection.
Aims
This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment.
Methods
CHC patients (
n
= 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β with/without Treg inhibition were also detected.
Results
The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4
+
Foxp3
+
T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT,
P
= 0.0393; EOT vs. SVR 12,
P
= 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-β was significantly increased at Week 4 and SVR 12 compared to baseline.
Conclusions
The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-β parallelled Treg function. |
| doi_str_mv | 10.1007/s10620-019-05850-w |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2299144269</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A712935788</galeid><sourcerecordid>A712935788</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-7909a2787b4846849757b3856518df6e09952f324db31ce8409d75e5d5404dc03</originalsourceid><addsrcrecordid>eNp9kUtv1DAUhS0EokPhD7BAltiwSfEjfi2jgVKkIhAMayvj3AyuEnuwHUr_PR6mUIEQ8sJXvt85vlcHoaeUnFFC1MtMiWSkIdQ0RGhBmut7aEWF4g0TUt9HK0JlrSmVJ-hRzleEEKOofIhOOBXCCMFX6PtH2C1TX2K6wRu8hmnC50twxceA38Xh0IIBd2OBhD8tzkHO4zLhVz6BK01XwbDDXSj-m0_9hDcJ-jJDKHiMCa-_pBi8wxew74svPuM1_lCr2s-P0YOxnzI8ub1P0efz15v1RXP5_s3bdXfZuLZlpVGGmJ4prbatbqVujRJqy7WQguphlECMEWzkrB22nDrQLTGDEiAG0ZJ2cISfohdH332KXxfIxc4-u7pnHyAu2TJmDK1fSVPR53-hV3FJoU53oJTgkhJ6R-36CawPYyypdwdT2ynKDBdK60qd_YOqZ4DZuxhg9PX9DwE7ClyKOScY7T75uU83lhJ7iNse47Y1bvszbntdRc9uJ162Mwy_Jb_yrQA_Arm2wg7S3Ur_sf0Bb66zRQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2297536101</pqid></control><display><type>article</type><title>Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Wu, Shu-Fen ; Tseng, Chih-Wei ; Ho, Yun-Che ; Chen, Yen-Chun ; Ko, Ping-Hung ; He, Yi-Ting ; Tseng, Kuo-Chih</creator><creatorcontrib>Wu, Shu-Fen ; Tseng, Chih-Wei ; Ho, Yun-Che ; Chen, Yen-Chun ; Ko, Ping-Hung ; He, Yi-Ting ; Tseng, Kuo-Chih</creatorcontrib><description>Backgrounds
Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection.
Aims
This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment.
Methods
CHC patients (
n
= 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β with/without Treg inhibition were also detected.
Results
The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4
+
Foxp3
+
T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT,
P
= 0.0393; EOT vs. SVR 12,
P
= 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-β was significantly increased at Week 4 and SVR 12 compared to baseline.
Conclusions
The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-β parallelled Treg function.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-019-05850-w</identifier><identifier>PMID: 31559553</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aged ; Antiviral Agents - therapeutic use ; Antiviral drugs ; Biochemistry ; Biological response modifiers ; Cytokines ; Cytokines - blood ; Drug therapy ; Female ; Gastroenterology ; Genotype ; Health aspects ; Hepacivirus - genetics ; Hepatitis ; Hepatitis C ; Hepatitis C virus ; Hepatitis C, Chronic - blood ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - virology ; Hepatology ; Humans ; Interferon ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Oncology ; Original Article ; RNA, Viral - blood ; Sustained Virologic Response ; T cells ; T-Lymphocytes, Regulatory - virology ; Transforming growth factors ; Transplant Surgery ; Tumor necrosis factor ; Tumor necrosis factor-TNF</subject><ispartof>Digestive diseases and sciences, 2020-05, Vol.65 (5), p.1385-1395</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-7909a2787b4846849757b3856518df6e09952f324db31ce8409d75e5d5404dc03</citedby><cites>FETCH-LOGICAL-c442t-7909a2787b4846849757b3856518df6e09952f324db31ce8409d75e5d5404dc03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10620-019-05850-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10620-019-05850-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31559553$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Shu-Fen</creatorcontrib><creatorcontrib>Tseng, Chih-Wei</creatorcontrib><creatorcontrib>Ho, Yun-Che</creatorcontrib><creatorcontrib>Chen, Yen-Chun</creatorcontrib><creatorcontrib>Ko, Ping-Hung</creatorcontrib><creatorcontrib>He, Yi-Ting</creatorcontrib><creatorcontrib>Tseng, Kuo-Chih</creatorcontrib><title>Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>Backgrounds
Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection.
Aims
This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment.
Methods
CHC patients (
n
= 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β with/without Treg inhibition were also detected.
Results
The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4
+
Foxp3
+
T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT,
P
= 0.0393; EOT vs. SVR 12,
P
= 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-β was significantly increased at Week 4 and SVR 12 compared to baseline.
Conclusions
The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-β parallelled Treg function.</description><subject>Aged</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Antiviral drugs</subject><subject>Biochemistry</subject><subject>Biological response modifiers</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Drug therapy</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Genotype</subject><subject>Health aspects</subject><subject>Hepacivirus - genetics</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - blood</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - virology</subject><subject>Hepatology</subject><subject>Humans</subject><subject>Interferon</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Original Article</subject><subject>RNA, Viral - blood</subject><subject>Sustained Virologic Response</subject><subject>T cells</subject><subject>T-Lymphocytes, Regulatory - virology</subject><subject>Transforming growth factors</subject><subject>Transplant Surgery</subject><subject>Tumor necrosis factor</subject><subject>Tumor necrosis factor-TNF</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kUtv1DAUhS0EokPhD7BAltiwSfEjfi2jgVKkIhAMayvj3AyuEnuwHUr_PR6mUIEQ8sJXvt85vlcHoaeUnFFC1MtMiWSkIdQ0RGhBmut7aEWF4g0TUt9HK0JlrSmVJ-hRzleEEKOofIhOOBXCCMFX6PtH2C1TX2K6wRu8hmnC50twxceA38Xh0IIBd2OBhD8tzkHO4zLhVz6BK01XwbDDXSj-m0_9hDcJ-jJDKHiMCa-_pBi8wxew74svPuM1_lCr2s-P0YOxnzI8ub1P0efz15v1RXP5_s3bdXfZuLZlpVGGmJ4prbatbqVujRJqy7WQguphlECMEWzkrB22nDrQLTGDEiAG0ZJ2cISfohdH332KXxfIxc4-u7pnHyAu2TJmDK1fSVPR53-hV3FJoU53oJTgkhJ6R-36CawPYyypdwdT2ynKDBdK60qd_YOqZ4DZuxhg9PX9DwE7ClyKOScY7T75uU83lhJ7iNse47Y1bvszbntdRc9uJ162Mwy_Jb_yrQA_Arm2wg7S3Ur_sf0Bb66zRQ</recordid><startdate>20200501</startdate><enddate>20200501</enddate><creator>Wu, Shu-Fen</creator><creator>Tseng, Chih-Wei</creator><creator>Ho, Yun-Che</creator><creator>Chen, Yen-Chun</creator><creator>Ko, Ping-Hung</creator><creator>He, Yi-Ting</creator><creator>Tseng, Kuo-Chih</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</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>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>20200501</creationdate><title>Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients</title><author>Wu, Shu-Fen ; Tseng, Chih-Wei ; Ho, Yun-Che ; Chen, Yen-Chun ; Ko, Ping-Hung ; He, Yi-Ting ; Tseng, Kuo-Chih</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-7909a2787b4846849757b3856518df6e09952f324db31ce8409d75e5d5404dc03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Antiviral drugs</topic><topic>Biochemistry</topic><topic>Biological response modifiers</topic><topic>Cytokines</topic><topic>Cytokines - blood</topic><topic>Drug therapy</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Genotype</topic><topic>Health aspects</topic><topic>Hepacivirus - genetics</topic><topic>Hepatitis</topic><topic>Hepatitis C</topic><topic>Hepatitis C virus</topic><topic>Hepatitis C, Chronic - blood</topic><topic>Hepatitis C, Chronic - drug therapy</topic><topic>Hepatitis C, Chronic - virology</topic><topic>Hepatology</topic><topic>Humans</topic><topic>Interferon</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Oncology</topic><topic>Original Article</topic><topic>RNA, Viral - blood</topic><topic>Sustained Virologic Response</topic><topic>T cells</topic><topic>T-Lymphocytes, Regulatory - virology</topic><topic>Transforming growth factors</topic><topic>Transplant Surgery</topic><topic>Tumor necrosis factor</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Shu-Fen</creatorcontrib><creatorcontrib>Tseng, Chih-Wei</creatorcontrib><creatorcontrib>Ho, Yun-Che</creatorcontrib><creatorcontrib>Chen, Yen-Chun</creatorcontrib><creatorcontrib>Ko, Ping-Hung</creatorcontrib><creatorcontrib>He, Yi-Ting</creatorcontrib><creatorcontrib>Tseng, Kuo-Chih</creatorcontrib><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>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Shu-Fen</au><au>Tseng, Chih-Wei</au><au>Ho, Yun-Che</au><au>Chen, Yen-Chun</au><au>Ko, Ping-Hung</au><au>He, Yi-Ting</au><au>Tseng, Kuo-Chih</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2020-05-01</date><risdate>2020</risdate><volume>65</volume><issue>5</issue><spage>1385</spage><epage>1395</epage><pages>1385-1395</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><abstract>Backgrounds
Regulatory T cells (Tregs) affect the pathogenesis of chronic hepatitis C (CHC) infection.
Aims
This study evaluated the function of Tregs in CHC patients receiving the standard direct-acting antiviral agents (DAA) treatment.
Methods
CHC patients (
n
= 20) who received DAA treatment, clinical data, and function of Tregs were checked at baseline, Week 4, end of treatment (EOT), and 12 weeks after EOT (SVR 12). Treg-mediated inhibition was measured. The cytokine expression and fold change of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β with/without Treg inhibition were also detected.
Results
The cohort included 14 females with a mean age of 59.8 ± 11.5 years. Nineteen had HCV genotype 1. The HCV RNA level was 6.17 ± 0.70 log IU/mL. All patients reached the sustained virologic response. The frequency of CD4
+
Foxp3
+
T cells decreased from baseline to EOT and returned at SVR 12. The inhibitory function of Tregs decreased during treatment and then restored (baseline vs. EOT,
P
= 0.0393; EOT vs. SVR 12,
P
= 0.0052). The cytokine expression and fold change of IFN-γ and TNF-α were highest at EOT and then decreased at SVR 12. The fold change of IL-10 was lowest at EOT and then increased at SVR 12. The fold change of TGF-β was significantly increased at Week 4 and SVR 12 compared to baseline.
Conclusions
The frequency and inhibitory function of Tregs declined gradually from baseline to EOT and then increased from EOT to SVR 12 in CHC patients receiving DAA therapy. The expression of IFN-γ, TNF-α, IL-10, and TGF-β parallelled Treg function.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>31559553</pmid><doi>10.1007/s10620-019-05850-w</doi><tpages>11</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0163-2116 |
| ispartof | Digestive diseases and sciences, 2020-05, Vol.65 (5), p.1385-1395 |
| issn | 0163-2116 1573-2568 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2299144269 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Aged Antiviral Agents - therapeutic use Antiviral drugs Biochemistry Biological response modifiers Cytokines Cytokines - blood Drug therapy Female Gastroenterology Genotype Health aspects Hepacivirus - genetics Hepatitis Hepatitis C Hepatitis C virus Hepatitis C, Chronic - blood Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - virology Hepatology Humans Interferon Male Medicine Medicine & Public Health Middle Aged Oncology Original Article RNA, Viral - blood Sustained Virologic Response T cells T-Lymphocytes, Regulatory - virology Transforming growth factors Transplant Surgery Tumor necrosis factor Tumor necrosis factor-TNF |
| title | Regulatory T Cell Function Modulated After Successful Direct-Acting Antiviral Treatment for Chronic Hepatitis C Patients |
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