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Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome.

ABSTRACT: B-cell differentiation and B-cell tolerance checkpoints may be different in antiphospholipid syndrome (APS) from systemic lupus erythematosus (SLE) and can help to understand differences between them. Our aim was to define alterations of B-cell subsets in patients with primary APS (pAPS) and to compare them with SLE patients and healthy controls (HC).Cross-sectional study including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age- and gender-matched HC. We determined the frequencies of different B-cell subsets in peripheral blood naïve and memory compartments. In addition, we measured serum B cell-activating factor (BAFF) levels and circulating pro-inflammatory cytokines, such as IL-6, by commercial ELISA and CBA, respectively.Patients with pAPS showed a lower percentage of immature and naïve B cells than patients with SLE (p = 0.013 and p = 0.010, respectively) and a higher percentage of non-switched memory B cells than patients with SLE (p = 0.001). No differences either in the percentage of switched memory cells or plasma cells were found among the different groups. Serum BAFF levels were higher in SLE patients than in healthy controls and pAPS patients (p = 0.001 and p = 0.017, respectively). A significant increase in the serum BAFF levels was also observed in pAPS patients compared to HC (p = 0.047). Circulating IL-6 levels were higher in SLE and pAPS patients than HC (p = 0.036 and p = 0.048, respectively). A positive correlation was found between serum BAFF and IL-6 levels in patients with SLE but not in pAPS (p = 0.011).Our characterization of peripheral blood B-cell phenotypes in pAPS demonstrates different frequencies of circulating B cells at different stages of differentiation. These differences in the naïve B-cell repertoire could explain the higher number and variety of autoantibodies in SLE patients in comparison to pAPS patients, especially in those with obstetric complications.

SUBMITTER: Alvarez-Rodriguez L

PROVIDER: S-EPMC5855811 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

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Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome.

Alvarez-Rodriguez Lorena L Riancho-Zarrabeitia Leyre L Calvo-Alén Jime J López-Hoyos Marcos M Martínez-Taboada Victor V

International journal of molecular sciences 20180216 2

<h4>Background</h4>B-cell differentiation and B-cell tolerance checkpoints may be different in antiphospholipid syndrome (APS) from systemic lupus erythematosus (SLE) and can help to understand differences between them. Our aim was to define alterations of B-cell subsets in patients with primary APS (pAPS) and to compare them with SLE patients and healthy controls (HC).<h4>Methods</h4>Cross-sectional study including three study groups: 37 patients with pAPS, 11 SLE patients, and 21 age- and gend ...[more]

PMID: 29462939

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Project description:Introduction: The role of the immune response in the pathogenesis of antiphospholipid syndrome (APS) remains elusive. It is possible that differences in the frequencies of Th17 cells and/or defects in the immunoregulatory mechanisms are involved in the pathogenesis of APS. Our aim was to determine the peripheral blood Th cells phenotype and the circulating cytokine profile in patients with primary APS (pAPS) and compare it with systemic lupus erythemathosus (SLE) as disease control group. Methods: The frequencies of circulating regulatory T cells (Tregs) were determined in PBMCs from 36 patients with pAPS by flow cytometry. As control groups we included 21 age- and gender-matched healthy controls (HC) and 11 patients with SLE. The suppressive capacity of Tregs was evaluated in vitro by coculture assay. On the other hand, intracellular cytokine production was assessed in Th1, Th2, and Th17 cells and circulating IL-6, IL-10, and IL-35 were measured by Cytometric Bead Array and ELISA. The quantification of Th master gene expression levels was performed by real time quantitative PCR. Results: pAPS patients and SLE patients did not show differences in the percentage or number of Tregs compared to HC. The suppressive capacity of Tregs was also similar in the three study group. Instead, we found higher FoxP3·mRNA expression levels in pAPS patients and HC than SLE patients. Regarding the Th17 response, patients with pAPS and HC showed a significantly lower frequency of circulating Th17 cells than SLE. However, no differences were observed in the Th1 response between patients and controls. Thus, increased Th17/Th1 and Th17/Treg ratios were found in SLE patients but not in pAPS patients. pAPS and SLE patients had higher serum IL-6 levels than HC but there was not difference between both disease groups. Besides, a significant increase in the immunosuppressive cytokine levels was observed only in pAPS as compared to HC. Conclusions: Our data demonstrate an increased inflammatory profile of peripheral blood CD4+ T cells from SLE as compared with pAPS mostly due to an increased Th17 response. In conclusion, there seems not to be a direct pathogenic role for Th cells in pAPS but in SLE.

Dataset Information

Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome.

Publications

Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome.

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