{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:50:53Z","timestamp":1787946653112,"version":"build-2784847793"},"reference-count":66,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Common variable immunodeficiency (CVID) is the most frequent primary antibody deficiency whereby follicular helper T (Tfh) cells fail to establish productive responses with B cells in germinal centers. Here, we analyzed the frequency, phenotype, transcriptome, and function of circulating Tfh (cTfh) cells in CVID patients displaying autoimmunity as an additional phenotype. A group of patients showed a high frequency of cTfh1 cells and a prominent expression of PD\u20101 and ICOS as well as a cTfh mRNA signature consistent with highly activated, but exhausted, senescent, and apoptotic cells. Plasmatic CXCL13 levels were elevated in this group and positively correlated with cTfh1 cell frequency and PD\u20101 levels. Monoallelic variants in\n                    <jats:italic>RTEL1<\/jats:italic>\n                    , a telomere length\u2010 and DNA repair\u2010related gene, were identified in four patients belonging to this group. Their blood lymphocytes showed shortened telomeres, while their cTfh were more prone to apoptosis. These data point toward a novel pathogenetic mechanism in CVID, whereby alterations in DNA repair and telomere elongation might predispose to antibody deficiency. A Th1, highly activated but exhausted and apoptotic cTfh phenotype was associated with this form of CVID.\n                  <\/jats:p>","DOI":"10.1002\/eji.202149480","type":"journal-article","created":{"date-parts":[[2022,5,14]],"date-time":"2022-05-14T00:18:10Z","timestamp":1652487490000},"page":"1171-1189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5401-5377","authenticated-orcid":false,"given":"Giulia","family":"Milardi","sequence":"first","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases Diabetes Research Institute IRCCS San Raffaele Hospital  Via Olgettina 60 Milan 20132 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6030-2583","authenticated-orcid":false,"given":"Biagio","family":"Di Lorenzo","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases Diabetes Research Institute IRCCS San Raffaele Hospital  Via Olgettina 60 Milan 20132 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6469-7378","authenticated-orcid":false,"given":"Jolanda","family":"Gerosa","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases Diabetes Research Institute IRCCS San Raffaele Hospital  Via Olgettina 60 Milan 20132 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4498-1712","authenticated-orcid":false,"given":"Federica","family":"Barzaghi","sequence":"additional","affiliation":[{"name":"Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Hospital  Via Olgettina 60 Milan 20132 Italy"},{"name":"Pathogenesis and therapy of primary immunodeficiencies Unit San Raffaele Telethon Institute for Gene Therapy Sr\u2010TIGET IRCCS San Raffaele Hospital  Via Olgettina 60 Milan 20132 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8344-5635","authenticated-orcid":false,"given":"Gigliola","family":"Di Matteo","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata  Via Cracovia 50 Rome 00133 Italy"},{"name":"Immune and Infectious Diseases Division, Research Unit of Primary Immunodeficiencies, Academic Department of Pediatrics Bambino Ges\u00f9 Children's Hospital IRCCS  Piazza di Sant'Onofrio 4 Rome 00165 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