scholarly journals THU0223 Elevated MTORC1 signature in B cells from sjÖgren's syndrome patients correlates with B cell hyperactivity that is abrogated by MTOR inhibition: a novel therapeutic strategy to halt B cell hyperactivity in PSS?

2017 ◽  
Author(s):  
SL Blokland ◽  
MR Hillen ◽  
CG Kommer-Wichers ◽  
AA Kruize ◽  
JC Broen ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Sjögren’S Syndrome ◽  
Therapeutic Strategy ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Mtor Inhibition ◽  
Novel Therapeutic ◽  
Sjögren‘S Syndrome

scholarly journals AB0025 B-CELL SUBSETS AS ADDITIONAL DIAGNOSTIC TOOL FOR PRIMARY SJOGREN’S SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1315.1-1316
Author(s):  
S. Benevolenskaya ◽  
I. Kudryavtsev ◽  
M. Serebriakova ◽  
I. Grigor’eva ◽  
A. Budkova ◽  
...  
Keyword(s):  
B Cells ◽  
Discriminant Analysis ◽  
B Cell ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Transitional B Cells ◽  
B Cell Subsets ◽  
Sjögren‘S Syndrome

Background:Systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome (pSS) are chronic complex disorders with an autoimmune background, multifactorial etiology, multiple circulating antinuclear antibodies and damage of various organs. SLE and pSS have several similar clinical and serological aspects; likewise, SLE and Sjögren’s syndrome may coexist (so-called secondary Sjögren’s syndrome). However, applied classification criteria do not differentiate SLE and pSS. It is known that humoral immunity plays significant part in pathogenesis of those diseases; hereby, we can expect imbalances in B cell subset frequencies during SLE and pSS.Objectives:To investigate clinical utility of B cell subsets in distinguish SLE and pSS during diagnosis.Methods:A total of 25 SLE patients, 25 SS patients and 49 healthy volunteers (HV) were included in the study. The diagnosis of SLE was performed according to the 2019 EULAR – ACR classification criteria, the diagnosis of pSS - according to the 2016 EULAR – ACR criteria. Phenotyping of blood B cell subsets was done using flow cytometry. Total peripheral blood B cells were identified using CD19 expression, distinct B cell subsets were characterized by IgD, CD38 and CD27 expression. All of the statistical analysis of data was performed with STATISTICA Version 12.0 Inc. (USA).Results:We evaluated the percentages of circulating B-cell subsets using three major classification schemes based on the relative co-expression of either IgD/CD38 (so-called “Bm1-Bm5” classification), IgD/CD27 and CD38/CD27. A discriminant analysis was performed for all B cell classifications. Analysis of CD38 and CD27 co-expression demonstrated most significant separation between patients with SLE and pSS (fig. 1). Moreover, discriminant analysis carried out by using a forward stepwise model demonstrated that the top significance was documented while assessing the percentage of plasmoblasts (CD27hiCD38hi), resting memory B-cells (CD27dimCD38low), mature active B-cells (CD27dimCD38dim), naive mature B-cells (CD27dimCD38low), as well as counting the absolute numbers of transitional B-cells (CD27lowCD38hi), model percent correct was 78,6% (p <0,05, tab.1).Figure 1.Graphic distribution of SLE and pSS patients as well as HV analyzed by discriminant analysis.Conclusion:B cell subsets might provide a useful diagnostic tool for distinction SLE and pSS. More research needed to investigate clinical value of B-cell subsets in autoimmune rheumatic diseases.Table 1.Peripheral B-cell subset composition in SLE and SS patients vs. HV group assessed by discriminant analysis.ParameterF-testp-levelPlasmoblasts (CD27hiCD38hi), %7,93<0.001Resting memory B-cells (CD27dimCD38low), %13,72<0.001Transitional B-cells (CD27lowCD38hi)29,74<0.001Mature active B-cells (CD27dimCD38dim), %5,20<0.001Naive mature B-cells (CD27dimCD38low), %3,100.049Double negative (CD27lowCD38low), %1,980,14Resting memory B-cells (CD27dimCD38low)1,020,36Double negative (CD27lowCD38low)2,320,10Plasmoblasts (CD27hiCD38hi)1,020,36Naive mature B-cells (CD27dimCD38low)1,030,36Mature active B-cells (CD27dimCD38dim)1,020,36Transitional B-cells (CD27lowCD38hi), %1,030,36Disclosure of Interests:None declared

scholarly journals B Cell Toll-like Receptors with Respect to the Pathogenesis of Sjögren’s Syndrome

2011 ◽  
Vol 54 (2) ◽  
pp. 51-57 ◽  
Author(s):  
Irena Berglová ◽  
Jan Krejsek ◽  
Martina Koláčková ◽  
Radovan Slezák
Keyword(s):  
B Cells ◽  
B Cell ◽  
Sjögren’S Syndrome ◽  
Lupus Erythematosus ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Toll Like Receptors ◽  
Glandular Secretion ◽  
Sjögren‘S Syndrome

Sjőgren’s syndrome (SS) is a chronic autoimmune immunopathological disease of unknown aetiology. It is characterized by focal lymphocyte infiltration and inflammation in exocrinne glands, involving especially salivary and lacrimal glands. Hypofunction of the glands leads to the decreased glandular secretion together with impaired production of saliva and tears, resulting in dryness of the mouth and eyes (xerostomia and xerophthalmia, respectively). Some of the studies have suggested that Toll-like receptors and B cells play a pivotal role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and SS etc. Stimulation of B cells via the TLRs pathway leads to several important changes including increase in antibody production, differentiation to plasma cells, cytokine production and up-regulation of molecules essential for antigen presentation to (autoreactive) T cells. Experimental data support the idea that co-engagement of BCR and TLR might be sufficient for B cell activation and lead to the failure of tolerance. In human naive B cells, most TLRs are expressed at very low or undetectable level, but expression of TLR 7 and 9 is rapidly induced by B cell receptor triggering. This review will focus on the possible role of B cells and TLRs signaling in the pathogenesis of SS.

scholarly journals Autoimmune B Cell Repertoire in a Mouse Model of Sjögren’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel Sáez Moya ◽  
Rebeca Gutiérrez-Cózar ◽  
Joan Puñet-Ortiz ◽  
María Luisa Rodríguez de la Concepción ◽  
Julià Blanco ◽  
...  
Keyword(s):  
B Cells ◽  
Mouse Model ◽  
B Cell ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Sjögren‘S Syndrome

In genetically prone individuals, chronic immune activation may lead to expansion of autoreactive lymphocyte clones that can induce organ damage developing autoimmune disorders. Sjögren’s Syndrome (SjS) is a systemic chronic autoimmune disease that primarily affects exocrine glands. Despite the accumulated evidences of profound B-cell alterations of humoral immunity, the repertoire and development of B-cell autoreactivity in SjS remains to be determined. We hypothesize that SjS mice will have an increased frequency of self-reactive B cells with a progressive evolution to antigen-driven oligoclonality. Here, we study the B cell repertoire of NOD.H-2h4 mice, a mouse model of spontaneous autoimmunity mimicking SjS without developing diabetes. A library of 168 hybridomas from NOD.H-2h4 mice and 186 C57BL/6J splenocytes at different ages was created. The presence of mono or polyreactive autoantibodies to several antigens was evaluated by ELISA, and their staining patterns and cellular reactivity were tested by IFA and FACS. We observed a higher frequency of autoreactivity among B-cell clones from NOD.H-2h4 mice as compared to wild-type mice. The presence of polyreactive and autoreactive IgG clones increased with mice age. Strikingly, all anti-Ro52 autoantibodies were polyreactive. No loss of polyreactivity was observed upon antibody class switching to IgG. There was a progression to oligoclonality in IgG B cells with mice aging. Our results indicate that in the NOD.H-2h4 mouse model of SjS, IgG+ B cells are mainly polyreactive and might expand following an unknown antigen-driven positive selection process.

scholarly journals The Multiple Roles of B Cells in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenhan Du ◽  
Man Han ◽  
Xiaoxia Zhu ◽  
Fan Xiao ◽  
Enyu Huang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Sjögren’S Syndrome ◽  
Lymphoid Tissue ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Exocrine Glands ◽  
B Cell Subsets ◽  
Sjögren‘S Syndrome

Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by lymphocytic infiltration and tissue destruction of exocrine glands such as salivary glands. Although the formation of ectopic lymphoid tissue in exocrine glands and overproduction of autoantibodies by autoreactive B cells highlight the critical involvement of B cells in disease development, the precise roles of various B cell subsets in pSS pathogenesis remain partially understood. Current studies have identified several novel B cell subsets with multiple functions in pSS, among which autoreactive age-associated B cells, and plasma cells with augmented autoantibody production contribute to the disease progression. In addition, tissue-resident Fc Receptor-Like 4 (FcRL4)+ B cell subset with enhanced pro-inflammatory cytokine production serves as a key driver in pSS patients with mucosa-associated lymphoid tissue (MALT)-lymphomas. Recently, regulatory B (Breg) cells with impaired immunosuppressive functions are found negatively correlated with T follicular helper (Tfh) cells in pSS patients. Further studies have revealed a pivotal role of Breg cells in constraining Tfh response in autoimmune pathogenesis. This review provides an overview of recent advances in the identification of pathogenic B cell subsets and Breg cells, as well as new development of B-cell targeted therapies in pSS patients.

scholarly journals Significance of B cells and B cell clonality in Sjögren's syndrome

2010 ◽  
Vol 62 (9) ◽  
pp. 2605-2610 ◽  
Author(s):  
Pierre Youinou ◽  
Valérie Devauchelle-Pensec ◽  
Jacques-Olivier Pers
Keyword(s):  
B Cells ◽  
B Cell ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Cell Clonality ◽  
Sjögren‘S Syndrome

scholarly journals Pathogenetic Mechanisms Implicated in Sjögren’s Syndrome Lymphomagenesis: A Review of the Literature

2020 ◽  
Vol 9 (12) ◽  
pp. 3794
Author(s):  
Ioanna E. Stergiou ◽  
Aikaterini Poulaki ◽  
Michael Voulgarelis
Keyword(s):  
Cell Proliferation ◽  
B Cells ◽  
B Cell ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Antigenic Stimulation ◽  
Chronic Antigenic Stimulation ◽  
Sjögren‘S Syndrome

Sjögren’s Syndrome (SS) is a chronic autoimmune disorder characterized by focal mononuclear cell infiltrates that surround the ducts of the exocrine glands, impairing the function of their secretory units. Compared to other autoimmune disorders, SS is associated with a notably high incidence of non-Hodgkin lymphoma (NHL) and more frequently mucosa associated lymphoid tissue (MALT) lymphoma, leading to increased morbidity and mortality rates. High risk features of lymphoma development include systemic extraepithelial manifestations, low serum levels of complement component C4 and mixed type II cryoglobulinemia. The discrimination between reactive and neoplastic lymphoepithelial lesion (LEL) is challenging, probably reflecting a continuum in the evolution from purely inflammatory lymphoid infiltration to the clonal neoplastic evolution. Early lesions display a predominance of activated T cells, while B cells prevail in severe histologic lesions. This strong B cell infiltration is not only a morphologic phenomenon, but it is also progressively associated with the presence of ectopic germinal centers (GCs). Ectopic formation of GCs in SS represents a complex process regulated by an array of cytokines, adhesion molecules and chemokines. Chronic antigenic stimulation is the major driver of specific B cell proliferation and increases the frequency of their transformation in the ectopic GCs and marginal zone (MZ) equivalents. B cells expressing cell surface rheumatoid factor (RF) are frequently detected in the salivary glands, suggesting that clonal expansion might arise from antigen selection of RF-expressing B cells. Abnormal stimulation and incomplete control mechanisms within ectopic lymphoid structures predispose RF MZ like cells to lymphoma development. Immunoglobulin recombination, somatic mutation and isotype switching during B cell development are events that may increase the translocation of oncogenes to immunoglobulin loci or tumor suppressor gene inactivation, leading to monoclonal B cell proliferation and lymphoma development. Concerning chronic antigenic stimulation, conclusive data is so far lacking. However immune complexes containing DNA or RNA are the most likely candidates. Whether additional molecular oncogenic events contribute to the malignant overgrowth remains to be proved.

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