Valter R Fonseca1, Vasco C Romão1, Ana Agua-Doce2, Mara Santos3, Dolores López-Presa3, Ana Cristina Ferreira3, João Eurico Fonseca1, Luis Graca2. 1. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte and Lisbon Academic Medical Center, Lisbon, Portugal. 2. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal, and Instituto Gulbenkian de Ciência, Oeiras, Portugal. 3. Hospital de Santa Maria, Centro Hospitalar Lisboa Norte and Lisbon Academic Medical Center, Lisbon, Portugal.
Abstract
OBJECTIVE: To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS). METHODS: We prospectively recruited 56 patients clinically suspected of having SS. Sixteen of these patients subsequently fulfilled the American-European Consensus Group criteria for SS and were compared to 16 patients with non-SS sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments. RESULTS: Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1-positive (PD-1+) inducible costimulator-positive (ICOS+) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs, being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell infiltration in MSGs, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P = 0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. CONCLUSION: The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.
OBJECTIVE: To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS). METHODS: We prospectively recruited 56 patients clinically suspected of having SS. Sixteen of these patients subsequently fulfilled the American-European Consensus Group criteria for SS and were compared to 16 patients with non-SS sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments. RESULTS:Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1-positive (PD-1+) inducible costimulator-positive (ICOS+) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs, being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell infiltration in MSGs, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P = 0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker. CONCLUSION: The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.
Authors: Rashi Gupta; Emma Vanlieshout; Kieran Manion; Dennisse Bonilla; Michael Kim; Carolina Muñoz-Grajales; Carol Nassar; Sindhu R Johnson; Linda T Hiraki; Zareen Ahmad; Zahi Touma; Arthur Bookman; Joan E Wither Journal: Front Immunol Date: 2022-06-30 Impact factor: 8.786
Authors: Filipa Ribeiro; Vasco C Romão; Sara Rosa; Kátia Jesus; Ana Água-Doce; Sofia C Barreira; Patrícia Martins; Susana Lopes da Silva; Ema Nobre; Maria João Bugalho; Válter R Fonseca; João Eurico Fonseca; Luis Graca Journal: Sci Rep Date: 2022-10-21 Impact factor: 4.996