Cells with regulatory function of the innate and adaptive immune system in primary Sjögren’s syndrome

Szodoray, Péter; Papp, Gábor; Horváth, Ildikó; Baráth, Sándor; Sipka, Sándor; Nakken, Britt; Zeher, Margit

doi:10.1111/j.1365-2249.2009.03966.x

Cited by 75 publications

(54 citation statements)

References 33 publications

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“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 The role of regulatory T cells in systemic autoimmune diseases and UCTD In line with this hypothesis, previous studies conducted on patients with systemic autoimmune and rheumatic disease described that the selective decrease in the number of Tregs or, alternatively, a diminished suppressor function of Tregs are characteristic to these diseases (e.g. SLE, MCTD, Sjögren's syndrome or RA [13][14][15][16][17]. These data indicate that in patients with established autoimmune conditions a well-characterized quantitative and/or qualitative impairment of the regulatory T-cell pool exists.…”

supporting

confidence: 52%

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Nakken

Bodolay

Szodoray

2014

Clinic Rev Allerg Immunol

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Undifferentiated connective tissue disease (UCTD) is a unique clinical entity, a potential forerunner of well-established systemic autoimmune/rheumatic diseases. UCTD is characterized by the presence of various clinical symptoms, as well as a diverse repertoire of autoantibodies, resembling systemic autoimmune diseases. Since approximately one-third of these patients consequently transform into a full-blown systemic autoimmune/rheumatic disease, it is of major importance to assess pathogenic factors leading to this progression. In view of the fact that the serological and clinical picture of UCTD and systemic autoimmune diseases are very similar, it is assumed that analogous pathogenic factors perpetuate both disease entities. In systemic autoimmune conditions a quantitative and qualitative impairment of regulatory T cells have been shown previously and in parallel a relative dominance of proinflammatory Th17 cells has been introduced. Moreover the imbalance between regulatory and Th17 cells plays a pivotal role in the initiation and propagation of UCTD. Additionally, we depict a cytokine imbalance, which give raise to a biased T-cell homeostasis from the UCTD phase throughout the fully developed systemic autoimmune disease stage. The levels of IL-6, IL-12, IL-17, IL-23 and IFN- were pathologically increased with a parallel reduction of IL-10. We believe that the assessment of Th17/Treg cell ratio, as well as the simultaneous quantitation of cytokines may give a useful diagnostic tool at the early UCTD stage to identify patients with a higher chance of consecutive disease progression towards serious systemic autoimmune diseases. Moreover, the early-targeted immunomodulating therapy in these patients may decelerate, or even stop this progression, before the development of serious autoimmune conditions with organ damage.

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supporting

confidence: 52%

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Nakken

Bodolay

Szodoray

2014

Clinic Rev Allerg Immunol

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“…For phenotypic analysis from heparinized blood samples we used CD3-fluorescein isothiocyanate (FITC), CD4-FITC, CD8-R-phycoerythrin (PE), CD19-R-phycoerythrinCyanine dye 5 (PE-Cy5), and CD16+CD56-PE (BD Biosciences, San Diego, CA, USA and For the identification of CD4 + T helper cell subsets we used intracytoplasmic cytokine staining method which has been described previously [25,26]. …”

Section: Determination Of Lymphocyte Subpopulationsmentioning

confidence: 99%

Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome

Szabó

Papp

Baráth

et al. 2013

Clinical Immunology

139

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“…The decreased IL-10-producing B reg cell percentages in pSS may elucidate our previous observations that, despite the increased peripheral IL-10-producing regulatory T (Tr1) cell proportions, a significant decrease in soluble IL-10 levels can be detected in the disease. We assume that, along with the decrease in IL-10 production of B reg cells, the intensification of a counterbalance mechanism appears; thus, levels of IL-10-producing Tr1 cells increase as a feedback process attempting to compensate the progression of disproportional immune responses [42].…”

Section: Cd27mentioning

confidence: 99%

A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjögren’s syndrome and systemic lupus erythematosus

Szabó

Papp

Szántó

et al. 2015

Clinical and Experimental Immunology

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108

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SummaryFollicular T helper (Tfh) cells have a crucial role in regulating immune responses within secondary lymphoid follicles by directing B cell differentiation towards memory B cells and plasma cells. Because abnormal humoral responses are key features in both primary Sj€ ogren's syndrome (pSS) and systemic lupus erythematosus (SLE), the aim of this study was to profile the pathological connection between peripheral Tfh cells and B cells in the two diseases. Twenty-five pSS patients, 25 SLE patients and 21 healthy controls were enrolled into the study. We determined the ratio of circulating Tfh-like cells, their interleukin (IL)-21 production and different B cell subsets by flow cytometry. We observed higher percentages of naive B cells in both diseases, while non-switched and switched memory B cells showed decreased frequencies. The proportions of double-negative B cells and plasmablasts were elevated in SLE and decreased in pSS. The percentages of transitional B cells and mature-naive B cells were higher in SLE. Patients with more severe disease course had an elevated ratio of T FHlike cells and increased IL-21 production. Moreover, expansion of Tfh-like cells correlated positively with parameters related to antibody secretion, including serum immunoglobulin (Ig)G, immune complexes (ICs) and autoantibodies. Correlation analysis between Tfh-like cells and certain B cell subsets revealed possible defects during B cell selection. In conclusion, our observations on the profound expansion of circulating Tfh-like cells and their IL-21 production, along with the characteristic aberrant peripheral B cell distribution in both pSS and SLE, indicate the prominent role of Tfh cell in the regulation of B cell selection.

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Cells with regulatory function of the innate and adaptive immune system in primary Sjögren’s syndrome

Abstract: SummaryThe aim of the present study was to describe subsets of cells with regulatory properties in primary Sjögren's syndrome (pSS) ,

Cited by 75 publications

References 33 publications

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Cytokine Milieu in Undifferentiated Connective Tissue Disease: a Comprehensive Review

Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome

A comprehensive investigation on the distribution of circulating follicular T helper cells and B cell subsets in primary Sjögren’s syndrome and systemic lupus erythematosus

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