PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis
Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T-...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/256 |
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| author | Miriana d’Alessandro Edoardo Conticini Laura Bergantini Fabrizio Mezzasalma Paolo Cameli Stefano Baglioni Martina Armati Marta Abbritti Elena Bargagli |
| author_facet | Miriana d’Alessandro Edoardo Conticini Laura Bergantini Fabrizio Mezzasalma Paolo Cameli Stefano Baglioni Martina Armati Marta Abbritti Elena Bargagli |
| author_sort | Miriana d’Alessandro |
| collection | DOAJ |
| description | Sarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T- and NK-cells negatively regulate the T-cell immune function. The present study aimed to explore the peripheral distribution of IC molecules to better elucidate their peripheral tolerance failure, which might reflect the development of diseases. Patients referred to Respiratory Diseases and Rheumatology Unit of Siena University Hospital were prospectively and consecutively enrolled. Healthy subjects were also enrolled as a control group. Multicolor flow cytometric analysis was performed to detect IC molecules in the peripheral blood of patients. Twenty-three patients were consecutively and prospectively enrolled in the study: 11 patients had an AAV diagnosis and 12 had sarcoidosis. CD4<sup>+</sup>PD1<sup>+</sup> cells were higher in sarcoidosis and GPA than in HC (<i>p</i> = 0.0250 and <i>p</i> = 0.0253, respectively). CD56<sup>+</sup>CTLA4<sup>+</sup> were higher in sarcoidosis than GPA, MPA and HC (<i>p</i> = 0.0085, <i>p</i> = 0.0042 and <i>p</i> = 0.0004, respectively). CTLA4<sup>+</sup>NK cells clustered for 100% of sarcoidosis patients according to decision tree analysis, while PD1<sup>+</sup>CD4 and CD8 cells for clustered for 100% of GPA patients. Our analyses showed substantial differences between sarcoidosis and AAV, further confirming the immunological peculiarity of this disease. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with the hope to open up new therapeutic avenues and, if possible, to develop preventive measures. |
| first_indexed | 2024-03-11T09:59:52Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:59:52Z |
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| spelling | doaj.art-754790c6b7ba4e29b8f4f2e86c682c6b2023-11-16T15:30:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124125610.3390/ijms24010256PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated VasculitisMiriana d’Alessandro0Edoardo Conticini1Laura Bergantini2Fabrizio Mezzasalma3Paolo Cameli4Stefano Baglioni5Martina Armati6Marta Abbritti7Elena Bargagli8Respiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, 53100 Siena, ItalyRheumatology Unit, Department of Medicine, Surgery & Neurosciences, University of Siena, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, 53100 Siena, ItalyDiagnostic and Interventional Bronchoscopy Unit, Cardio-Thoracic and Vascular Department, University Hospital of Siena Azienda Ospedaliera Universitaria Senese, AOUS, 53100 Siena, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, 53100 Siena, ItalyPneumology Department, Perugia Hospital, 06129 Perugia, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, 53100 Siena, ItalyPneumology Department, Perugia Hospital, 06129 Perugia, ItalyRespiratory Diseases and Lung Transplantation Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, 53100 Siena, ItalySarcoidosis is a granulomatous diseases affecting the lungs. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a histologically granulomatous B-mediated disorder characterized by activated T cells. The expression of immune checkpoint (IC) molecules (PD1, CTLA4, TIGIT) on T- and NK-cells negatively regulate the T-cell immune function. The present study aimed to explore the peripheral distribution of IC molecules to better elucidate their peripheral tolerance failure, which might reflect the development of diseases. Patients referred to Respiratory Diseases and Rheumatology Unit of Siena University Hospital were prospectively and consecutively enrolled. Healthy subjects were also enrolled as a control group. Multicolor flow cytometric analysis was performed to detect IC molecules in the peripheral blood of patients. Twenty-three patients were consecutively and prospectively enrolled in the study: 11 patients had an AAV diagnosis and 12 had sarcoidosis. CD4<sup>+</sup>PD1<sup>+</sup> cells were higher in sarcoidosis and GPA than in HC (<i>p</i> = 0.0250 and <i>p</i> = 0.0253, respectively). CD56<sup>+</sup>CTLA4<sup>+</sup> were higher in sarcoidosis than GPA, MPA and HC (<i>p</i> = 0.0085, <i>p</i> = 0.0042 and <i>p</i> = 0.0004, respectively). CTLA4<sup>+</sup>NK cells clustered for 100% of sarcoidosis patients according to decision tree analysis, while PD1<sup>+</sup>CD4 and CD8 cells for clustered for 100% of GPA patients. Our analyses showed substantial differences between sarcoidosis and AAV, further confirming the immunological peculiarity of this disease. Despite these advances, the pathogenesis remains incompletely understood, indicating an urgent need for further research to reveal the distinct immunological events in this process, with the hope to open up new therapeutic avenues and, if possible, to develop preventive measures.https://www.mdpi.com/1422-0067/24/1/256sarcoidosisANCA-associated vasculitisimmune checkpoint molecules |
| spellingShingle | Miriana d’Alessandro Edoardo Conticini Laura Bergantini Fabrizio Mezzasalma Paolo Cameli Stefano Baglioni Martina Armati Marta Abbritti Elena Bargagli PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis International Journal of Molecular Sciences sarcoidosis ANCA-associated vasculitis immune checkpoint molecules |
| title | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
| title_full | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
| title_fullStr | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
| title_full_unstemmed | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
| title_short | PD1, CTLA4 and TIGIT Expression on T and NK Cells in Granulomatous Diseases: Sarcoidosis and ANCA-Associated Vasculitis |
| title_sort | pd1 ctla4 and tigit expression on t and nk cells in granulomatous diseases sarcoidosis and anca associated vasculitis |
| topic | sarcoidosis ANCA-associated vasculitis immune checkpoint molecules |
| url | https://www.mdpi.com/1422-0067/24/1/256 |
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