Journal Article

Expansion of CD57+ CD8 T cells in common variable immunodeficiency with hepatopathy and CMV infection

Goldacker, Sigune, Warnatz, Klaus, Santangeli, Enrico, Salzer, Ulrich, Bez, Patrick

2025

Overview

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. 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 CD8 T cells. Patients on immunosuppressive therapy were excluded. The expansion of CD57 CD8 T cells was part of the previously described immune alteration, including altered CD4/CD8 ratio and a decrease in naïve 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 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. 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, 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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adolescent / Adult / Aged / Bacterial infections / CD4 antigen / CD45RA antigen / CD57 / CD57 antigen / CD57 Antigens - immunology / CD57 Antigens - metabolism / CD8 antigen / CD8 T cells / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - metabolism / Cloning / CMV infection / Common variable immunodeficiency / common variable immunodeficiency (CVID) / Common Variable Immunodeficiency - complications / Common Variable Immunodeficiency - immunology / Cytomegalovirus - immunology / Cytomegalovirus Infections - immunology / diagnosis / Diarrhea / Female / Genetic testing / Granuloma / Granulomas / Homeostasis / Humans / Hypertension / immune phenotype / Immune system / Immunology / Immunosenescence / Immunosuppressive agents / Liver diseases / Liver Diseases - immunology / Lung diseases / Lymphadenopathy / Lymphocytes / Lymphocytes T / Male / Middle Aged / Phenotypes / Retrospective Studies / Splenectomy / Splenomegaly / Variables / Young Adult