Journal of clinical immunology · 2026
Immunopathological Profile of Patients with Thymic Epithelial Tumour and Good Syndrome in Advanced Stage.
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Napolitano Fabiana, Pietroluongo Erica, Di Tolla Michele Francesco, Ottaviano Margaret, D'Esposito Vittoria, De Placido Pietro, Servetto Alberto, Portella Giuseppe, Bianco Roberto, Palmieri Giovannella, Formisano Pietro, Malfitano Anna Maria
Аннотация
PURPOSE: Thymic epithelial tumors (TETs) are associated with Good Syndrome (GS), a secondary immunodeficiency characterized by hypogammaglobulinemia, B-cell lymphopenia, and recurrent infections. This study investigated the immunological profile of TET patients to identify immune alterations associated with GS, independently of autoimmune diseases (AD) and disease stage.
METHODS: Seventy patients with TETs were stratified according to GS status (GS+/GS-), AD status (AD+/AD-), and disease stage (advanced disease, IVA/B, or no evidence of disease, NED). Serum immunoglobulins, peripheral immune cell subsets, and circulating cytokines, chemokines, growth factors, and metabolic markers were evaluated.
RESULTS: GS+ patients showed reduced IgM and IgG levels compared with GS- patients; however, after stratification, only IgM remained reduced in GS+AD- NED patients. Peripheral B-cell lymphopenia was consistently observed in GS+ patients across both disease stages, independently of AD status. Treg frequencies increased in GS- patients with advanced disease and in GS+AD+ NED patients. Monocytopenia and an inverted CD4+/CD8+ ratio were mainly observed in GS+AD+ patients with advanced disease. Cytokine profiling identified increased levels of IL-1β, IL-10, IL-17, TNFα, IFN-γ, IL-4, IL-5, IL-6, Eotaxin, G-CSF, and IP-10 in GS+ patients. Among these, IP-10 remained consistently elevated regardless of disease stage or AD status.
CONCLUSION: Peripheral B-cell lymphopenia and elevated IP-10 levels represent the most consistent immunological features associated with GS, independent of disease stage and AD status, whereas serum immunoglobulin levels appear less reliable in advanced disease. These findings support the diagnostic value of immunophenotyping, particularly B-cell quantification and IP-10 measurement, for identifying GS in patients with TETs.
METHODS: Seventy patients with TETs were stratified according to GS status (GS+/GS-), AD status (AD+/AD-), and disease stage (advanced disease, IVA/B, or no evidence of disease, NED). Serum immunoglobulins, peripheral immune cell subsets, and circulating cytokines, chemokines, growth factors, and metabolic markers were evaluated.
RESULTS: GS+ patients showed reduced IgM and IgG levels compared with GS- patients; however, after stratification, only IgM remained reduced in GS+AD- NED patients. Peripheral B-cell lymphopenia was consistently observed in GS+ patients across both disease stages, independently of AD status. Treg frequencies increased in GS- patients with advanced disease and in GS+AD+ NED patients. Monocytopenia and an inverted CD4+/CD8+ ratio were mainly observed in GS+AD+ patients with advanced disease. Cytokine profiling identified increased levels of IL-1β, IL-10, IL-17, TNFα, IFN-γ, IL-4, IL-5, IL-6, Eotaxin, G-CSF, and IP-10 in GS+ patients. Among these, IP-10 remained consistently elevated regardless of disease stage or AD status.
CONCLUSION: Peripheral B-cell lymphopenia and elevated IP-10 levels represent the most consistent immunological features associated with GS, independent of disease stage and AD status, whereas serum immunoglobulin levels appear less reliable in advanced disease. These findings support the diagnostic value of immunophenotyping, particularly B-cell quantification and IP-10 measurement, for identifying GS in patients with TETs.