Aberrant expression of CD6 on B-cell subsets from patients with 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

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

Frontiers in Immunology ◽

10.3389/fimmu.2021.684999 ◽

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.

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