Abstract
Introduction: Belimumab is a monoclonal antibody against soluble BLyS used for treatment of refractory Systemic Lupus Erythematosus (SLE). Although B cells are the main target of this therapy, a BLyS-dependent T cell activation pathway has also been demonstrated. The aim of the study is to analyze B and T cells phenotype modifications in a cohort of SLE patients treated with belimumab in correlation with serum BLyS levels.Materials and Methods: Fourteen SLE patients were enrolled in the study. Lymphocyte immunophenotyping by flow cytometry and determination of serum BLyS levels by high sensitivity ELISA were performed before the first infusion of belimumab, after 6 and 12 months of treatment. Sex and age-matched healthy controls were enrolled for the comparisons.Results: Baseline number of total B cells, especially switched memory B cells, were lower in SLE patients compared to control subjects. After 6 months of treatment, the total number of B cells, particularly, naive and transitional B cells, was significantly reduced in correlation with the reduction of BLyS levels. No significant association was found between baseline counts of B cells and reduction of SLEDAI-2K over time. In terms of response prediction, a significant association between SLEDAI-2K improvement at 12 months and the decrease of total number of B cells within the first 6 months of therapy was observed. Concerning the T cell compartment, the baseline percentage number of CD8+ effector memory was associated with SLEDAI-2K at baseline and with its improvement after 12 months of therapy. Furthermore, T cell lymphopenia and low number of circulating recent thymic emigrants were also observed compared to control subjects measured at baseline.Discussion: The effects of belimumab on B cell subpopulations could be explained by the direct blockage of soluble BLyS, while the mild effects on T cells might be explained indirectly by the reduction of disease activity by means of therapy. B cell immunophenotyping during belimumab might be useful for monitoring the response to treatment.
Highlights
Belimumab is a monoclonal antibody against soluble BLyS used for treatment of refractory Systemic Lupus Erythematosus (SLE)
As previously reported (Piantoni et al, 2018), T cell lymphopenia was observed in patients with SLE, with increased percentages of effector cells
Since lymphopenia is a common clinical manifestation and one of the classification criteria for SLE (Hochberg, 1997), the low absolute number of B and T cells observed in our patients at baseline were expected
Summary
Belimumab is a monoclonal antibody against soluble BLyS used for treatment of refractory Systemic Lupus Erythematosus (SLE). Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of several autoantibodies. Both innate and adaptive immunity are involved in the pathogenesis of the disease, but recent evidences showed that adaptive immunity has a central role (Mak and Kow, 2014). SLE patients have a severe defect in the B cell tolerance check, resulting in high numbers of autoreactive mature naïve B cells, which subsequently give rise to autoantibody producing plasma cells (Vossenkämper et al, 2011). The defect most likely occurs at the transitional stage between new bone marrow emigrants and mature naïve B cells in the periphery; an expansion of transitional B cells may be detected in peripheral blood of SLE patients (Vossenkämper et al, 2011). The mechanisms of selection of transitional B cells in humans are not yet fully understood (Sims et al, 2005); a crucial signal for the B cell development through this stage is thought to be delivered by B lymphocyte stimulator (BLyS, known as BAFF), a member of the tumor necrosis factor superfamily (Mackay et al, 2010)
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