ORIGINAL RESEARCH article
Front. Immunol.
Sec. Primary Immunodeficiencies
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1577934
EXPANSION OF CD57 + CD8 T CELLS IN COMMON VARIABLE IMMUNODEFICIENCY (CVID) WITH HEPATOPATHY AND CMV INFECTION
Provisionally accepted
- 1Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Freiburg, Germany
- 2Center for Chronic Immunodeficiency, University of Freiburg Medical Center, Freiburg, Germany
- 3Rare Diseases Referral Center, Internal Medicine I, Ca’ Foncello Hospital, AULSS2 Marca Trevigiana, Treviso, Italy
- 4Department of Pediatrics, ASST Spedali Civili of Brescia, Department of Clinical and Experimental Sciencies, University of Brescia, Brescia, Italy, Brescia, Italy
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Background: Common variable immunodeficiency (CVID) is associated with an altered immune homeostasis affecting many T cell subpopulations including an increased proportion of CD57+ 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+ CD8 T cells in CVID patients and determine its diagnostic value. Methods: 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 ESID criteria and at least two independent assessments of CD57+ CD8 T cells. Patients on immunosuppressive therapy were excluded. Results: The expansion of CD57+ CD8 T cells was part of the previously described immune alteration including altered CD4/CD8 ratio and decrease in naïve CD4 T cells. The loss of significant association with increasing age might corroborate the suggest premature immunosenescence in CVID. Significant higher values of CD57+ 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+ CD8 T cell values. When comparing the potential diagnostic value of expanded CD57+ 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+ CD8 T cell counts were superior to more commonly used T cell populations, except for CMV infection. Conclusion: This is the largest study on the prevalence and diagnostic relevance of the expansion of CD57+ CD8 T cells in CVID. Most CD57+ CD8 T cells are part of the CD45RA+ terminal effector subset. While we could not detect an added value of the diagnostic evaluation of CD57+ CD8 T cells at this time, its 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.
Keywords: Common variable immunodeficiency (CVID), Immune phenotype, diagnosis, CD8 T cells, CD57, CMV infection, Hepatopathy, Splenomegaly
Received: 17 Feb 2025; Accepted: 30 Apr 2025.
Copyright: © 2025 BEZ, Santangeli, Goldacker, Salzer and Warnatz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Klaus Warnatz, Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Freiburg, 79106, Germany
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