Association between memory B-cells and clinical and immunological features of primary Sjögren’s syndrome and Sicca patients

Barcelos, Filipe; Martins, Catarina; Papoila, Ana Luísa; Geraldes, Carlos F. G. C.; Cardigos, Joana; Nunes, Glória; Lopes, Teresa; Alves, Nuno L.; Patto, José Vaz; Branco, Jaime; Borrego, Luís Miguel

doi:10.1007/s00296-018-4018-0

Cited by 14 publications

(9 citation statements)

References 38 publications

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“…This of interest, because clinical data of patients in this study suggest comparable trends, with cases in JIA-Uveitis 2 showing longer disease duration compared to the other groups. In contrast, in B cell-mediated inflammatory conditions such as Sjogren's disease longer disease duration is associated with a decrease in memory B cell subsets and a more active disease profile (37). Furthermore, although age-related changes in memory B cell subsets have been reported, the absolute number of peripheral blood naïve and memory B cell subsets both decline from ±2-4 years old until adulthood (30).…”

Section: Discussionmentioning

confidence: 99%

Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis

et al. 2020

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Purpose: Patients with juvenile idiopathic arthritis (JIA) are prone to developing chronic anterior uveitis (JIA-U+). Although several risk factors for JIA-U+ have been identified, the underlying etiology is poorly understood. Histopathological studies demonstrate B cell infiltrates in eye tissues of patients with JIA-U+. Methods: We performed transcriptome profiling of peripheral blood CD19-positive B cells taken from 14 cases with JIA-U+, 13 JIA cases without uveitis (JIA-U−), and five healthy controls. Deconvolution-based estimation was used to determine the immune cell fractions for each sample. Results: Deconvolution results revealed that naive B cells made up on average 71% of the CD19-positive cell fractions analyzed. Differential expression analysis identified 614 differentially expressed genes (DEGs) between the groups at nominal significance and six genes at a false discovery rate of 5% (FDR < 0.05). Head-to-head comparison of all JIA-U− versus JIA-U+ revealed no DEGs in the CD19+ B cell pool (FDR < 0.05). However, principal component analysis based on a panel of key genes for B cell subsets revealed that JIA-U+ cases bifurcate into distinct clusters, characterized by markedly disparate expression for genes associated with specific memory B cell populations. CIBERSORT analysis of the overall transcriptome of the new uveitis cluster identified an increased proportion of memory B cells. Conclusion: These data show that JIA-U− and JIA-U+ have a globally similar transcriptome considering the global peripheral CD19-positive B cell pool. However, heterogeneity in B cell memory genes among cases with uveitis suggests a role for specific memory B cell subsets in the etiology of JIA-U+.

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Section: Discussionmentioning

confidence: 99%

Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis

et al. 2020

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“…2014; Barcelos et al. 2018). These B‐cell disturbances in SjS may represent the presence of a more immature component in transit to target organs and a shift in maturation towards the plasma cell lineage.…”

Section: Discussionmentioning

confidence: 99%

Corneal sub‐basal nerve plexus assessment and its association with phenotypic features and lymphocyte subsets in Sjögren's Syndrome

Barcelos

Hipólito-Fernandes

Martins

et al. 2021

Acta Ophthalmologica

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To assess and compare corneal sub-basal nerve plexus morphology with circulating lymphocyte subsets, immunologic status and disease activity in Sj€ ogren syndrome (SjS) patients.Methods: Fifty-five SjS patients, 63 Sicca patients (not fulfilling SjS criteria), 18 rheumatoid arthritis (RA) patients and 20 healthy controls (HC) were included. Systemic disease activity in SjS was assessed with the ESSDAI score. Lymphocyte subpopulations were studied with flow cytometry. Corneal confocal microscopy and ImageJ software were used to characterize corneal sub-basal nerve plexus in terms of nerve density (CNFD), length (CNFL) and tortuosity (CNFT). Conventional dry eye tests were also performed.Results: CNFL and CNFD were lower in SjS, Sicca and RA groups, compared to HC (p < 0.001 for both SjS and Sicca); CNFL p = 0.005, CNFD p = 0.018 in RA). CNFT was higher in SjS, followed by Sicca, RA and HC. A negative correlation was found between ESSDAI score and CNFL (r=À0.735, p = 0.012). CNFL correlated negatively with IL21 + CD8 + T cells (r=À0.279, p = 0.039) and a positively with total memory (r = 0.299, p = 0.027), unswitched memory (r = 0.281, p = 0.038) and CD24 Hi CD27 + (r = 0.278, p = 0.040) B cells. CNFD showed a tendency to significance in its negative correlation with ESSDAI (r=À0.592, p = 0.071) and in its positive correlation with switched memory B cells (r = 0.644, p = 0.068).Conclusions: This is the first study aiming to correlate ocular findings with lymphocyte subsets in SjS. The associations founded between CNFL and CNFD and disease activity, IL21 + follicular T cells and some B-cell subsets suggest that corneal nerve damage may parallel systemic disease activity and inflammatory cells' dynamics.

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“…On the other hand, there is strong evidence of unbalance of B cell subpopulations also in SS. Many authors found that memory and switched memory B cells are reduced in primary SS compared to controls (86)(87)(88), and this unbalance appears to be related to disease duration and activity (88). Saadoun et al found an increase of CD21 low/-B cells in primary SS and in particular in primary SS with lymphoproliferative disorders, suggesting a key role of this B cell population in SS related lymphomagenesis (89,90).…”

Section: Ss and B-cell Abnormalitiesmentioning

confidence: 99%

Section: Common Features Between Cvid and Sjögren’s Syndromementioning

confidence: 99%

Shared Pathogenetic Features Between Common Variable Immunodeficiency and Sjögren’s Syndrome: Clues for a Personalized Medicine

Quartuccio

Marchi²,

Longhino

et al. 2021

Front. Immunol.

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Common variable immunodeficiency disorders (CVID) are a group of rare diseases of the immune system and the most common symptomatic primary antibody deficiency in adults. The “variable” aspect of CVID refers to the approximately half of the patients who develop non-infective complications, mainly autoimmune features, in particular organ specific autoimmune diseases including thyroiditis, and cytopenias. Among these associated conditions, the incidence of lymphoma, including mucosal associated lymphoid tissue (MALT) type, is increased. Although these associated autoimmune disorders in CVID are generally attributed to Systemic Lupus Erythematosus (SLE), we propose that Sjogren’s syndrome (SS) is perhaps a better candidate for the associated disease. SS is an autoimmune disorder characterized by the lymphocytic infiltrates of lacrimal and salivary glands, leading to dryness of the eyes and mouth. Thus, it is a lymphocyte aggressive disorder, in contrast to SLE where pathology is generally attributed to auto-antibody and complement activation. Although systemic lupus erythematosus (SLE) shares these features with SS, a much higher frequency of MALT lymphoma distinguishes SS from SLE. Also, the higher frequency of germ line encoded paraproteins such as the monoclonal rheumatoid factor found in SS patients would be more consistent with the failure of B-cell VDJ switching found in CVID; and in contrast to the hypermutation that characterizes SLE autoantibodies. Thus, we suggest that SS may fit as a better “autoimmune” association with CVID. Examining the common underlying biologic mechanisms that promote lymphoid infiltration by dysregulated lymphocytes and lymphoma in CVID may provide new avenues for treatment in both the diseases. Since the diagnosis of SLE or rheumatoid arthritis is usually based on specific autoantibodies, the associated autoimmune features of CVID patients may not be recognized in the absence of autoantibodies.

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Association between memory B-cells and clinical and immunological features of primary Sjögren’s syndrome and Sicca patients

Cited by 14 publications

References 38 publications

Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis

Whole Transcriptome Analysis Reveals Heterogeneity in B Cell Memory Populations in Patients With Juvenile Idiopathic Arthritis-Associated Uveitis

Corneal sub‐basal nerve plexus assessment and its association with phenotypic features and lymphocyte subsets in Sjögren's Syndrome

Shared Pathogenetic Features Between Common Variable Immunodeficiency and Sjögren’s Syndrome: Clues for a Personalized Medicine

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