Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes
IntroductionGiant Cell Arteritis (GCA) is the most common vasculitis in the elderly, characterized by granulomatous infiltration of immune cells in medium and large arteries. A therapeutic protocol that combines ultra-short glucocorticoids (GC) followed by tocilizumab (TCZ) monotherapy has been prov...
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Frontiers Media S.A.
2025-03-01
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| author | Cecilia Catellani Martina Bonacini Alessandro Rossi Ilaria Ferrigno Ilaria Ferrigno Veronica Buia Chiara Marvisi Chiara Marvisi Giulia Cassone Mariagrazia Catanoso Gabriella Di Tommaso Luigi Boiardi Rexhep Durmo Annibale Versari Massimiliano Casali Giulia Besutti Giulia Besutti Lucia Spaggiari Alessandro Zerbini Francesco Muratore Francesco Muratore Carlo Salvarani Carlo Salvarani Stefania Croci |
| author_facet | Cecilia Catellani Martina Bonacini Alessandro Rossi Ilaria Ferrigno Ilaria Ferrigno Veronica Buia Chiara Marvisi Chiara Marvisi Giulia Cassone Mariagrazia Catanoso Gabriella Di Tommaso Luigi Boiardi Rexhep Durmo Annibale Versari Massimiliano Casali Giulia Besutti Giulia Besutti Lucia Spaggiari Alessandro Zerbini Francesco Muratore Francesco Muratore Carlo Salvarani Carlo Salvarani Stefania Croci |
| author_sort | Cecilia Catellani |
| collection | DOAJ |
| description | IntroductionGiant Cell Arteritis (GCA) is the most common vasculitis in the elderly, characterized by granulomatous infiltration of immune cells in medium and large arteries. A therapeutic protocol that combines ultra-short glucocorticoids (GC) followed by tocilizumab (TCZ) monotherapy has been proven effective in GCA patients with extracranial large vessel involvement (LV-GCA). However, its effects on circulating immune cells are unknown. The aim of this study was to deepen the understanding of the immunological mechanisms behind this treatment regimen in patients with LV-GCA.Methods15 patients with active LV-GCA were included in this study. Blood samples were collected at baseline, after 3 days of GC treatment, at weeks 24 and 52 during TCZ monotherapy, and at week 78 after the suspension of TCZ. Peripheral blood mononuclear cells were isolated from blood samples. The percentages of lymphocyte and monocyte subsets and the expression of the monocyte markers CCR2, CX3CR1, and HLA-DR were analyzed by flow cytometry. Paired Student’s t-test and mixed-effects analysis were used for the comparison between and among groups, respectively.ResultsGC boluses increased the percentages of B lymphocytes and classical monocytes while decreased those of CD4+ T lymphocytes and intermediate and non-classical monocytes. Moreover, GC boluses increased CCR2 and decreased HLA-DR and CX3CR1 expression by monocytes. TCZ induced a reduction in CCR2 expression versus baseline in classical and intermediate monocytes. Patients with higher reduction in CCR2 expression in intermediate monocytes at 24 weeks and 52 weeks versus baseline showed signs of disease activity at 78 weeks.ConclusionGC boluses modified the relative percentages of lymphocyte and monocyte subsets and modified the expression levels of CCR2, CX3CR1, and HLA-DR in monocytes. These changes may contribute to the anti-inflammatory effects of GCs. TCZ monotherapy had more limited effects. Changes in CCR2 expression by intermediate monocytes might have a prognostic value in LVV. |
| format | Article |
| id | doaj-art-995b8a05cb9e4b3884d05c4ab2c99337 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
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| series | Frontiers in Immunology |
| spelling | doaj-art-995b8a05cb9e4b3884d05c4ab2c993372025-08-20T02:10:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15160081516008Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytesCecilia Catellani0Martina Bonacini1Alessandro Rossi2Ilaria Ferrigno3Ilaria Ferrigno4Veronica Buia5Chiara Marvisi6Chiara Marvisi7Giulia Cassone8Mariagrazia Catanoso9Gabriella Di Tommaso10Luigi Boiardi11Rexhep Durmo12Annibale Versari13Massimiliano Casali14Giulia Besutti15Giulia Besutti16Lucia Spaggiari17Alessandro Zerbini18Francesco Muratore19Francesco Muratore20Carlo Salvarani21Carlo Salvarani22Stefania Croci23Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyPhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyPhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, Modena, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Nuclear Medicine, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Nuclear Medicine, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyNuclear Medicine Unit, Azienda Unità Sanitaria Locale di Piacenza, Piacenza, ItalyDepartment of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, ItalyUnit of Radiology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Radiology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyDepartment of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyDepartment of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, ItalyIntroductionGiant Cell Arteritis (GCA) is the most common vasculitis in the elderly, characterized by granulomatous infiltration of immune cells in medium and large arteries. A therapeutic protocol that combines ultra-short glucocorticoids (GC) followed by tocilizumab (TCZ) monotherapy has been proven effective in GCA patients with extracranial large vessel involvement (LV-GCA). However, its effects on circulating immune cells are unknown. The aim of this study was to deepen the understanding of the immunological mechanisms behind this treatment regimen in patients with LV-GCA.Methods15 patients with active LV-GCA were included in this study. Blood samples were collected at baseline, after 3 days of GC treatment, at weeks 24 and 52 during TCZ monotherapy, and at week 78 after the suspension of TCZ. Peripheral blood mononuclear cells were isolated from blood samples. The percentages of lymphocyte and monocyte subsets and the expression of the monocyte markers CCR2, CX3CR1, and HLA-DR were analyzed by flow cytometry. Paired Student’s t-test and mixed-effects analysis were used for the comparison between and among groups, respectively.ResultsGC boluses increased the percentages of B lymphocytes and classical monocytes while decreased those of CD4+ T lymphocytes and intermediate and non-classical monocytes. Moreover, GC boluses increased CCR2 and decreased HLA-DR and CX3CR1 expression by monocytes. TCZ induced a reduction in CCR2 expression versus baseline in classical and intermediate monocytes. Patients with higher reduction in CCR2 expression in intermediate monocytes at 24 weeks and 52 weeks versus baseline showed signs of disease activity at 78 weeks.ConclusionGC boluses modified the relative percentages of lymphocyte and monocyte subsets and modified the expression levels of CCR2, CX3CR1, and HLA-DR in monocytes. These changes may contribute to the anti-inflammatory effects of GCs. TCZ monotherapy had more limited effects. Changes in CCR2 expression by intermediate monocytes might have a prognostic value in LVV.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516008/fullgiant cell arteritisglucocorticoidstocilizumablymphocytesmonocytesCCR2 |
| spellingShingle | Cecilia Catellani Martina Bonacini Alessandro Rossi Ilaria Ferrigno Ilaria Ferrigno Veronica Buia Chiara Marvisi Chiara Marvisi Giulia Cassone Mariagrazia Catanoso Gabriella Di Tommaso Luigi Boiardi Rexhep Durmo Annibale Versari Massimiliano Casali Giulia Besutti Giulia Besutti Lucia Spaggiari Alessandro Zerbini Francesco Muratore Francesco Muratore Carlo Salvarani Carlo Salvarani Stefania Croci Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes Frontiers in Immunology giant cell arteritis glucocorticoids tocilizumab lymphocytes monocytes CCR2 |
| title | Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes |
| title_full | Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes |
| title_fullStr | Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes |
| title_full_unstemmed | Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes |
| title_short | Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes |
| title_sort | glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients effects on peripheral blood monocytes and lymphocytes |
| topic | giant cell arteritis glucocorticoids tocilizumab lymphocytes monocytes CCR2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1516008/full |
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