{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T00:53:14Z","timestamp":1794012794733,"version":"4.8.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T00:00:00Z","timestamp":1528416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Italian Minister of Public Health","award":["Project GR-2010-2313255"],"award-info":[{"award-number":["Project GR-2010-2313255"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Alteration of T-follicular helper (TFH) and regulatory (TFR) subpopulations may contribute to the development of auto-reactive B-cell.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To investigate whether changes in TFH and TFR subsets are associated with abnormal IgG synthesis in blood and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Paired blood and CSF samples were obtained from 31 untreated relapsing-remitting multiple sclerosis (RRMS) patients at diagnosis. Peripheral blood TFH (CD3+CD4+CXCR5+CD25\u2013CD127+), TFR (CD3+CD4+CXCR5+CD25+CD127\n                      <jats:sup>dim<\/jats:sup>\n                      ), conventional T-Helper (TH, CD3+CD4+CXCR5\u2013CD25\u2013CD127+), and regulatory T-cells (T-Reg, CD3+CD4+CXCR5\u2013CD25+CD127\n                      <jats:sup>dim<\/jats:sup>\n                      ) were analyzed in all RRMS patients and in 13 healthy controls (HCs). Qualitative and quantitative intrathecal IgG synthesis was evaluated in RRMS patients, who were then further subclassified according to the presence of IgG oligoclonal bands in blood and\/or CSF.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Compared to HC, RRMS had lower TFR percentage ( p &lt; 0.01) and higher TFH\/TFR ratio ( p &lt; 0.001). In RRMS, TFH\/TFR ratio correlated with both qualitative ( r = 0.56, p &lt; 0.005) and quantitative intrathecal IgG synthesis (IgG Index: r = 0.78; IgGLoc: r = 0.79; IgGIF: r = 0.76, all p &lt; 0.001). Patients with the highest TFH\/TFR ratios had higher percentages of circulating B-cells (36.1 \u00b1 35.2%, p &lt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>In RRMS, increased TFH\/TFR ratio associates with abnormal IgG production in blood and CSF, suggesting that antibody-producing cells, derived from deregulated peripheral germinal center reaction, colonize the CNS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1352458518779951","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T05:59:44Z","timestamp":1528437584000},"page":"918-926","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["Peripheral imbalanced TFH\/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset"],"prefix":"10.1177","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2313-8462","authenticated-orcid":false,"given":"Marco","family":"Puthenparampil","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Centre, Department of Neuroscience DNS, Universit\u00e0 degli Studi di Padova, via Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Zito","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Department of Neuroscience DNS, Universit\u00e0 degli Studi di Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Pantano","sequence":"additional","affiliation":[{"name":"Central Laboratory, Azienda Ospedaliera di Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Federle","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Ospedale San Bortolo di Vicenza, Azienda ULSS 8 Berica, Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Stropparo","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Department of Neuroscience DNS, Universit\u00e0 degli Studi di Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Miante","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Department of Neuroscience DNS, Universit\u00e0 degli Studi di Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giustina","family":"De Silvestro","sequence":"additional","affiliation":[{"name":"UOC Immunotrasfusionale, Azienda Ospedaliera di Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Plebani","sequence":"additional","affiliation":[{"name":"Central Laboratory, Azienda Ospedaliera di Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Gallo","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Department of Neuroscience DNS, Universit\u00e0 degli Studi di Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,6,8]]},"reference":[{"key":"bibr1-1352458518779951","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1100648"},{"key":"bibr2-1352458518779951","doi-asserted-by":"crossref","unstructured":"Lucchinetti CF, Br\u00fcck W, Rodriguez M, et al. 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