Lymphocyte subpopulations in Sjögren’s syndrome are distinct in anti-SSA-positive patients and related to disease activity

Barcelos, Filipe; Martins, Catarina; Madeira, Nathalie; Ângelo-Dias, Miguel; Cardigos, Joana; Alves, Nuno L.; Patto, José Vaz; Branco, Jaime; Borrego, Luís Miguel

doi:10.1007/s10067-020-05537-y

Cited by 7 publications

(6 citation statements)

References 47 publications

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“…Patients with autoimmune diseases, including pSS and SLE, and display alterations of these phenotypes in peripheral blood. In pSS, some studies have found a higher expression of Tfh2 and Tfh17 subsets (9,34), but others a higher prevalence of CXCR5+ Th1 and a lower prevalence of CXCR5+Th17 when comparing positive anti-Ro/SSA patients versus the seronegative group (35). A study that included the peripheral blood of patients with SLE, pSS, and controls found a positive correlation between circulating Tfh-cells and IgG and RF serum levels.…”

Section: Discussionmentioning

confidence: 99%

Differential Th follicular cell subsets in minor salivary glands of patients with primary Sjögren's syndrome and systemic lupus erythematosus associated with Sjögren's syndrome

Hernández-Molina

Soto‐Abraham

Zamora-Legoff

et al. 2021

Clinical and Experimental Rheumatology

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Objective. T follicular helper cells (Tfh) have been recognised in minor salivary glands (MSG) of patients with primary Sjögren's syndrome (pSS). Nevertheless, if the Tfh1, Tfh2, Tfh17, Tfr phenotype is different when comparing pSS and associated SS in systemic lupus erythematosus (SLE) is unknown. Methods. We included MSG biopsies from 8 pSS, 8 SLE/SS patients, 7 SLE patients, and 2 non-SS sicca patients. To determine the subpopulation of Tfh, a double-staining procedure for transcription factor B cell lymphoma 6 (Bcl-6)+/IL-17A+, Bcl6+/IL-4+, Bcl6+/IFN-γ+, and Bcl6+/Foxp3+ cells was performed. We estimated the mean percentage of positively staining cells in four fields per sample. Results. Tfh1, Tfh2, and Tfh17 cells were highly expressed in pSS compared with the rest of the groups; conversely, in patients with SLE/SS predominated, the Tfh17 and in SLE patients the Tfh1 cells. Regulatory Tfh cells (Tfr) were similar in pSS and the rest of the patients. However, the lowest frequency was found in the SLE group. A positive correlation was observed between anti-Ro/SSA autoantibody and Tfh17 subset (r=0.726, p=0.0001); and with the (Tfh2+Tfh17)/ Tfh1 ratio (r=0.844, p<0.0001) in the MSG of patients with pSS. Conclusion. We showed a differential Tfh profile in primary SS and SLE with associated SS. Whether this Tfh differential profile participates in the increased risk of lymphoproliferative disease in pSS compared with associated SS, or other outcomes, is yet to be determined in future studies.

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Section: Discussionmentioning

confidence: 99%

Differential Th follicular cell subsets in minor salivary glands of patients with primary Sjögren's syndrome and systemic lupus erythematosus associated with Sjögren's syndrome

Hernández-Molina

Soto‐Abraham

Zamora-Legoff

et al. 2021

Clinical and Experimental Rheumatology

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“…This divergence in pSS B cell subtype composition has previously been reported using flow cytometry. 27 Migration of memory B cells from the peripheral blood to the salivary glands has been proposed as a mechanism for this observation. 28 By analyzing a large number of individual B cells, we show an up-regulation of IFN-response genes across all B cell subtypes in all pSS groups relative to controls, with the most prominent signal in the SSA/SSB+ patient group.…”

Section: Discussionmentioning

confidence: 99%

Multimodal Single‐Cell Sequencing of B Cells in Primary Sjögren's Syndrome

Arvidsson,

Czarnewski,

Johansson

et al. 2023

Arthritis & Rheumatology

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ObjectiveB cells are important in the pathogenesis of primary Sjögren's syndrome (pSS). Patients positive for SSA/SSB autoantibodies are more prone to systemic disease manifestations and adverse outcomes. We aimed to determine the role of B cell composition, gene expression and B cell receptor (BCR) usage in pSS subgroups stratified for SSA/SSB antibodies.MethodsOver 230 000 B cells were isolated from peripheral blood of pSS patients (n = 6 SSA‐, n = 8 SSA+ single positive and n = 10 SSA/SSB+ double positive) and four healthy controls, and processed for single cell RNA and VDJ sequencing.ResultsWe show that SSA/SSB+ patients present the highest and lowest proportion of naïve and memory B cells respectively, and the highest upregulation of interferon‐induced genes across all B cell subtypes. Differential usage of IGHV showed that IGHV1‐69 and IGHV4‐30‐4 were more often used in all pSS subgroups compared with controls. Memory B cells from SSA/SSB+ patients displayed a higher proportion of cells with unmutated VDJ transcripts compared to other pSS patient groups and controls, indicating altered somatic hypermutation processes. Comparison with previous studies revealed heterogeneous clonotype pools, with little overlap in CDR3 sequences. Joint analysis using scRNA‐seq and scVDJ‐seq data allowed unsupervised stratification pSS patients, and identified novel parameters that correlated to disease manifestations and antibody status.ConclusionWe describe heterogeneity and molecular characteristics in B cells from pSS patients, providing clues to intrinsic differences in B cells that affect the phenotype and outcome, allowing stratification of pSS patients at improved resolution.This article is protected by copyright. All rights reserved.

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“…Indeed, patients from the group with anti-SSA antibodies not detected in CIE had a weak pSS systemic expression, similar to those without anti-SSA antibodies (HR = 0.59 [0.13–2.66]). They also shared general characteristics, notably a close age at diagnosis, and were more than ten years older than patients with positivity on CIE; whereas, it is known in the literature that patients with anti-SSA antibodies are around 10 years younger compared with those without these antibodies [ 7 , 9 , 10 , 11 , 12 , 13 ]. Patients from the SSA+CIE− group clearly presented less frequent signs of B lymphocyte hyperactivity compared with patients with positive CIE. To summarise, the clinical and biological phenotypes of the patients with anti-SSA antibodies for only denaturing methods appeared as if they had no anti-SSA antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Over the past three decades, anti-SSA antibodies have been largely associated with extraglandular involvement in pSS [ 7 , 9 , 10 , 11 , 12 , 13 ]. Sandhya et al noticed an odds ratio of 2.67 [1.09–6.54] of having an extraglandular manifestation in pSS patients presenting anti-SSA antibodies [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, anti-SSA antibodies are a criterion in classification consensus, including the actual ACR/EULAR 2016 consensus [ 8 ]. Beyond their use as a diagnostic criteria, the presence of anti-SSA antibodies has been associated with early onset disease, more signs of B cell activity (hypergammaglobulinemia, rheumatoid factors, cryoglobulinemia, and naive/memory B cell imbalance), and more extraglandular manifestations in pSS [ 7 , 9 , 10 , 11 , 12 , 13 ]: Raynaud phenomenon [ 14 ], interstitial pneumonia [ 15 ], peripheral nerve involvement [ 14 , 16 , 17 , 18 ], cutaneous vasculitis [ 19 , 20 , 21 , 22 ], cytopenias [ 16 , 19 , 23 , 24 ], adenopathies [ 14 , 19 , 25 ], and lymphoma [ 12 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Discordant Predictions of Extraglandular Involvement in Primary Sjögren’s Syndrome According to the Anti-SSA/Ro60 Antibodies Detection Assay in a Cohort Study

Urbanski

Gury

Jeannin

et al. 2022

JCM

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Electrophoresis-derived techniques for anti-SSA/Ro60 KDa (anti-SSA) antibodies detection have been progressively replaced by methods using non-native antigens. We aimed to compare the patients’ phenotypes and the occurrence of extraglandular manifestations in primary Sjögren’s syndrome according to the method used to detect anti-SSA antibodies. Sera from patients with a diagnosis of pSS according to ACR/EULAR 2016 criteria between 2008 and 2017 were tested for anti-SSA antibodies using methods with non-native antigens (magnetic bead multiplex assay; line immunoassays) and one with native antigens (counterimmunoelectrophoresis (CIE)). The population was split into three groups according to anti-SSA antibodies status: absence (SSA−), presence in any method except for CIE (SSA+CIE−), and presence in CIE (SSA+CIE+). The patients in the SSA+CIE+ group (n = 70, 42.7%) were ten years younger and presented more immunological activity compared with both the SSA− (n = 80, 48.8%) and SSA+CIE− groups (n = 14, 8.5%). The SSA− and SSA+CIE− groups were poorly distinct. The presence of anti-SSA antibodies solely in CIE was significantly associated with the occurrence of extraglandular manifestations of pSS (HR = 4.45 (2.35–8.42)). Contrary to CIE, methods using non-native antigens to detect anti-SSA antibodies were unable to predict the occurrence of systemic expression of pSS.

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Lymphocyte subpopulations in Sjögren’s syndrome are distinct in anti-SSA-positive patients and related to disease activity

Cited by 7 publications

References 47 publications

Differential Th follicular cell subsets in minor salivary glands of patients with primary Sjögren's syndrome and systemic lupus erythematosus associated with Sjögren's syndrome

Differential Th follicular cell subsets in minor salivary glands of patients with primary Sjögren's syndrome and systemic lupus erythematosus associated with Sjögren's syndrome

Multimodal Single‐Cell Sequencing of B Cells in Primary Sjögren's Syndrome

Discordant Predictions of Extraglandular Involvement in Primary Sjögren’s Syndrome According to the Anti-SSA/Ro60 Antibodies Detection Assay in a Cohort Study

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