{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:32:55Z","timestamp":1791387175796,"version":"4.3.3"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Common variable immunodeficiency (CVID) is associated with an altered immune homeostasis affecting many T-cell subpopulations, including an increased proportion of CD57<jats:sup>+<\/jats:sup> CD8 T lymphocytes. This expansion has been associated with the clinical manifestation of granuloma\/lymphadenopathy and a positive CMV status. The aim of the study is to describe the prevalence of an expansion of CD57<jats:sup>+<\/jats:sup> CD8 T cells in CVID patients and determine its diagnostic value.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a monocentric retrospective study including 131 patients with a median follow-up of 9 years. The inclusion criteria are a diagnosis of CVID according to European Society for Immunodeficiencies (ESID) criteria and at least two independent assessments of CD57<jats:sup>+<\/jats:sup> CD8 T cells. Patients on immunosuppressive therapy were excluded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expansion of CD57<jats:sup>+<\/jats:sup> CD8 T cells was part of the previously described immune alteration, including altered CD4\/CD8 ratio and a decrease in na\u00efve CD4 T cells. The loss of significant association with increasing age might corroborate the suggestion of premature immunosenescence in CVID. Significantly higher values of CD57<jats:sup>+<\/jats:sup> CD8 T cells were seen in patients with a complicated clinical phenotype, and especially associated with the presence of splenomegaly, status post-splenectomy, and hepatic disease. Additionally, patients with a history of CMV infection presented with elevated CD57<jats:sup>+<\/jats:sup> CD8 T cell values. When comparing the potential diagnostic value of expanded CD57<jats:sup>+<\/jats:sup> CD8 T cells compared to alterations in other T-cell subsets in relation to specific complications, we could not identify a single complication in CVID patients for which absolute or relative CD57<jats:sup>+<\/jats:sup> CD8 T cell counts were superior to more commonly used T-cell populations, except for CMV infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the largest study on the prevalence and diagnostic relevance of the expansion of CD57<jats:sup>+<\/jats:sup> CD8 T cells in CVID. Most CD57<jats:sup>+<\/jats:sup> CD8 T cells are part of the CD45RA<jats:sup>+<\/jats:sup> terminal effector subset. While we could not detect an added value of the diagnostic evaluation of CD57<jats:sup>+<\/jats:sup> CD8 T cells at this time, further investigation in circulation and tissue might enhance our understanding of the pathogenesis of hepatic disease and thereby gain novel diagnostic value in the future.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1577934","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T05:24:25Z","timestamp":1748323465000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Expansion of CD57+ CD8 T cells in common variable immunodeficiency with hepatopathy and CMV infection"],"prefix":"10.3389","volume":"16","author":[{"given":"Patrick","family":"Bez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Santangeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigune","family":"Goldacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Salzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jaip.2015.07.025","article-title":"International consensus document (ICON): common variable immunodeficiency 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