Peripheral B-Cell Subset Distribution in Primary Antiphospholipid Syndrome

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.

Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome

“…APS and SLE share some clinical features, such as multiorgan manifestations, and the aPL profile and complement activation. At the same time, there are differences in the serum autoantibodies detected in both syndromes and we have recently demonstrated that the B cell phenotype differs between pAPS and SLE ( 8 ). From a pathogenic point of view, both entities are inflammatory disorders in which the activation of the innate immune response triggers an exacerbated acquired immune response ( 9 ).…”

Follicular helper and follicular regulatory T cell subset imbalance is associated with higher activated B cells and abnormal autoantibody production in primary anti-phospholipid syndrome patients

“…Abnormal B cell maturation and differentiation is the underlying cause of this autoantibody production, and numerous studies have triggered a great deal of interest in the possibility of a crucial role for activated B cells and B cell subsets in the pathophysiology of autoimmune diseases, including rheumatoid arthritis (RA), Sjögren's syndrome (SS), multiple sclerosis (MS) and systemic lupus erythematosus (SLE) [5][6][7][8]. Furthermore, the dysfunction of B cell activation and B cell subset levels have also been suggested to be associated with the development of pAPS, but the phenotype changes of B cells and the potential mechanisms of B cell changes and autoantibody generation remain unknown [9][10][11].…”

Utilization of physiologically‐based pharmacokinetic model to assess disease‐mediated therapeutic protein‐disease‐drug interaction in immune‐mediated inflammatory diseases

“…The systemic IL‐6 levels collected from previous studies of various IMID populations were highly varied, as show in Figure 1 , ranging from 3.6 to 30.2 pg/ml in SLE, 1.3 to 85 pg/ml in UC, 4.25 to 47 pg/ml in CD, and 2.1 to 187 pg/ml in T1D. 11 , 13 , 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 The calculated mean ± SD of systemic IL‐6 levels were 12.7 ± 8.5, 23.9 ± 27.6, 20.6 ± 19.8, 56.7 ± 75.6 pg/ml in SLE, UC, CD, and T1D patient populations, respectively. The reported local GI tissue IL‐6 concentration in patients with UC and CD were also highly variable: 917–5885 pg/ml for UC and 704–7649 pg/ml for CD based on patient‐derived cell culture.…”

“…Literature data of systemic baseline IL‐6 levels in healthy subjects 22 and in patients with UC, CD, SLE and T1D, 11 , 13 , 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 and baseline IL‐6 levels in the local GI tract of patients with UC and CD were collected and examined. 43 , 49 , 50 , 51 , 52 , 53 The systemic or local IL‐6 concentrations obtained from different studies were pooled and the average IL‐6 levels with associated variability was calculated with GraphPad (GraphPad Software, Inc.).…”