Modulation of immune surface molecules associated with the efficacy of antiviral therapy for chronic hepatitis C virus infection

• Main Authors: Ya-Ling Wei, 魏雅鈴
• Other Authors: Kung-Chia Young
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/74461008454444588958

碩士 === 國立成功大學 === 醫學檢驗生物技術學系 === 94 === Hepatitis　C　virus　(HCV)　diseases　threaten　global　human　health.　The　current　treatment　for　chronic　HCV　infection　with　combination　regimen　of　pegylated　interferon　(IFN)-alpha　and　ribavirin　can　exert　overall　response　rate　of　approximately　46-78%,　which　is　influenced　by　viral　genotype,　initial　circulating　viral　load　and　host　factors.　Host　factors　such　as　immunological　regulators　seem　to　affect　the　outcome　of　antiviral　treatment　of　pegylated　IFN-alpha　and　ribavirin　since　both　agents　are　known　immumodulators.　Proper　antigen　presentation　function　is　required　to　elicit　sufficient　adapted　cellular　immunity　against　viral　infection,　which　has　been　impaired　in　patients　chronically　infected　with　HCV.　This　study　aims　to　investigate　whether　the　modulation　of　immuno-surface　proteins　by　pegylated　interferon　(IFN)-alpha　and　ribavirin　is　related　to　therapeutic　responses.　We　enrolled　35　patients　with　chronic　hepatitis　C,　who　have　undergone　combination　therapy.　We　longitudinally　assessed　the　effect　of　anti-HCV　agents　on　the　expression　levels　of　CD81,　HLA-ABC,　CD86　and　CD28,　the　three　major　components　in　trigger　of　antigen-dependent　and　antigen-independent　co-stimulatory　signals,　in　peripheral　blood　mononuclear　cells　(PBMCs)　from　patients　receiving　combination　therapy　for　24　weeks　and　afterward　follow-up　for　24　weeks.　FACS　analysis　showed　that　HLA-ABC　and　CD86　upregulation　on　B　cells　during　combine　therapy　in　patients　with　sustained　virological　response　(SVR)　(n=26),　but　not　in　patients　without　SVR　(n=9).　Elevation　of　surface　HLA-ABC　expression　was　not　secondary　to　increased　RNA　levels　in　B　cells.　The　treatment　induced　upregulation　of　surface　CD28　in　CD4+　and　CD8+　T　cells　in　both　of　the　patient　groups.　The　analysis　of　polymorphic　HLA-ABC　alleles　showed　no　significant　difference　in　both　patient　groups.　In　conclusion,　the　expression　levels　of　HLA-ABC　and　CD86　were　up-regulated　on　B　cells　during　combination　therapy　only　in　patients　with　SVR　but　not　non-SVR.