Filipe Barcelos1,2,3,4, Catarina Martins5,6, Nathalie Madeira7, Miguel Ângelo-Dias5, Joana Cardigos8, Nuno Alves8,9, José Vaz-Patto7, Jaime Cunha-Branco5,6,10,11, Luís-Miguel Borrego5,6,12. 1. CEDOC, Chronic Diseases Research Center, Immunology, NOVA Medical School | FCM, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056, Lisbon, Portugal. fduartebarcelos@gmail.com. 2. Comprehensive Health Research Centre (CHRC), NOVA Medical School / FCM, Universidade Nova de Lisboa, Lisbon, Portugal. fduartebarcelos@gmail.com. 3. Rheumatology Department, Instituto Português de Reumatologia, Lisbon, Portugal. fduartebarcelos@gmail.com. 4. Rheumatology Department, Hospital CUF Descobertas, Lisbon, Portugal. fduartebarcelos@gmail.com. 5. CEDOC, Chronic Diseases Research Center, Immunology, NOVA Medical School | FCM, Universidade Nova de Lisboa, Campo dos Mártires da Pátria, 130, 1169-056, Lisbon, Portugal. 6. Comprehensive Health Research Centre (CHRC), NOVA Medical School / FCM, Universidade Nova de Lisboa, Lisbon, Portugal. 7. Rheumatology Department, Instituto Português de Reumatologia, Lisbon, Portugal. 8. Ophthalmology Department, Centro Hospitalar de Lisboa Central, Hospital de Santo António dos Capuchos, Lisbon, Portugal. 9. Ophthalmology Department, Hospital CUF Descobertas, Lisbon, Portugal. 10. Rheumatology Department, Hospital CUF Descobertas, Lisbon, Portugal. 11. Rheumatology Department, Centro Hospitalar de Lisboa Ocidental, Hospital de Egas Moniz, Lisbon, Portugal. 12. Immunoalergy Department, Hospital da Luz Lisboa, Lisbon, Portugal.
Abstract
OBJECTIVES: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS. METHODS: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad PrismTM, with statistical significance concluded if p < 0.05. RESULTS: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ T cells (p = 0.046, r = 0.451). CONCLUSIONS: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21+CD4+ and IL-21+CD8+ (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy.
OBJECTIVES: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS. METHODS: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad PrismTM, with statistical significance concluded if p < 0.05. RESULTS: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ T cells (p = 0.046, r = 0.451). CONCLUSIONS: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21+CD4+ and IL-21+CD8+ (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy.
Entities:
Keywords:
B lymphocytes; Disease activity; SSA; Sjögren’s syndrome; T lymphocytes
Authors: Stina Salomonsson; Malin V Jonsson; Kathrine Skarstein; Karl A Brokstad; Peter Hjelmström; Marie Wahren-Herlenius; Roland Jonsson Journal: Arthritis Rheum Date: 2003-11
Authors: Caroline H Shiboski; Stephen C Shiboski; Raphaèle Seror; Lindsey A Criswell; Marc Labetoulle; Thomas M Lietman; Astrid Rasmussen; Hal Scofield; Claudio Vitali; Simon J Bowman; Xavier Mariette Journal: Arthritis Rheumatol Date: 2016-10-26 Impact factor: 10.995