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Direct-acting antiviral (DAA) therapies are effective in achieving sustained virologic response (SVR), however, whether successful DAA treatment reconstitute T follicular helper (T<jats:sub>FH<\/jats:sub>)-B cell axis in HCV patients is unclear. Here, we aimed to evaluate the immunological changes in global and HCV-specific CD4\u2009+\u2009CXCR5\u2009+\u2009T<jats:sub>FH<\/jats:sub>, CD4\u2009+\u2009CXCR5-T and B cells in 20 HCV patients who achieved SVR with Sofosbuvir and Ledipasvir for 12\u00a0weeks and compared with 15 healthy controls (HC). Global and HCV-specific CD4\u2009+\u2009CXCR5\u2009+\u2009T<jats:sub>FH<\/jats:sub>, CD4\u2009+\u2009CXCR5-T and CD19\u2009+\u2009B cells had significant phenotypic and functional reconstitution post DAA therapy. Reconstitution of effector, central and terminally differentiated memory cell population and increased ICOS and BCL6 expression was seen in HCV patients at SVR12. HCV-specific cytokines were also improved post DAA. Exhausted and regulatory B cells were declined whereas memory B cells were expanded post DAA therapy. Importantly, frequencies of T<jats:sub>FH<\/jats:sub> cells were significantly associated with HCV RNA reduction, expansion of memory B and plasmablasts, while negatively associated with exhausted\/regulatory B cells. Our results demonstrate that SVR with DAA therapy is effective in the reconstitution of phenotypic and functional abnormalities of T<jats:sub>FH<\/jats:sub>-B cell axis.<\/jats:p>","DOI":"10.1038\/s41598-020-77020-2","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T11:04:19Z","timestamp":1605524659000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Reconstitution of T follicular helper-humoral immune axis with elimination of hepatitis C virus"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6045-6884","authenticated-orcid":false,"given":"Arshi","family":"Khanam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shyamasundaran","family":"Kottilil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,16]]},"reference":[{"key":"77020_CR1","unstructured":"1World Health Organization. 2017. 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E.W. received grants paid to the institution from Gilead Sciences. S.K.: Received grants paid to the institution from Merck, Gilead and Arbutus. Advisory panel for Gilead and Merck.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"19924"}}