Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome.

Lorena Álvarez-Rodríguez,Jaime Calvo-Alén,Marcos López-Hoyos,Leyre Riancho-Zarrabeitia,Víctor Martínez-Taboada

doi:10.3390/ijms19020589

Abstract

Background: 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). Methods: 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. Results: 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). Conclusions: 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.

Highlights

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized serologically by the presence of antiphospholipid antibodies and at least one clinical event defined as vascular thrombosis and/or pregnancy morbidity [1]. aPL are a heterogeneous group of autoantibodies, which includes lupus anticoagulant (LA), immunoglobulin (Ig) G and IgM anti-cardiolipin antibodies, and anti-β2 glycoprotein I antibodies
To study possible alterations of B-cell subsets, we first determined the absolute number of peripheral blood CD19+ B cells in the peripheral blood of both patients and healthy controls
There were no significant differences in the circulating B cells among the different groups (226.5 cells/mm3 (181.8–341.3) versus 185 cells/mm3 (140.5–296) versus 112 cells/mm3 (87–325) in healthy controls (HC), primary APS (pAPS), and systemic lupus erythematosus (SLE) respectively, p = 0.184) (Table 1)

Summary

Introduction

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized serologically by the presence of antiphospholipid antibodies (aPL) and at least one clinical event defined as vascular thrombosis and/or pregnancy morbidity [1]. aPL are a heterogeneous group of autoantibodies, which includes lupus anticoagulant (LA), immunoglobulin (Ig) G and IgM anti-cardiolipin antibodies (aCL), and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Alterations of B-cell activation and B-cell subsets contribute to the development of autoimmune diseases, such as rheumatoid arthritis (RA), type 1 diabetes (T1D), Sjögren syndrome (SS), multiple sclerosis (MS), and systemic lupus erythematosus (SLE) [7,8,9,10]. Serum BAFF levels were higher in SLE patients than in healthy controls and pAPS patients (p = 0.001 and p = 0.017, respectively). Conclusions: 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

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