Abstract
Psoriasis (Ps), an autoimmune disease, and multiple myeloma (MM), a blood neoplasm, are characterized by immune dysregulation resulting from the imbalance between the effector and regulatory cells, including B regulatory (Breg) lymphocytes. Peripheral blood samples from 80 Ps patients, 17 relapsed/refractory MM patients before and after daratumumab (anti-CD38 monoclonal antibody) treatment, 23 healthy volunteers (HVs), and bone marrow samples from 59 MM patients were used in the study. Bregs were determined by flow cytometry using CD19, CD24, and CD38. Intracellular production of interleukin-10 (IL-10) was assessed by flow cytometry after CD40L, LPS, and CpG stimulation. IL-10 serum or plasma concentrations were tested using ELISA method. The percentage of CD19+CD24hiCD38hi Bregs was not different whereas the production of IL-10 in Bregs was significantly higher in Ps patients in comparison with HVs. The percentage of CD19+CD24hiCD38hi Bregs in MM patients was significantly higher than in HVs (p < 0.0001). The percentage of CD19+CD24hiCD38hi Bregs was significantly higher in MM patients with the ISS stage I (p = 0.0233) while IL-10 production in Bregs was significantly higher in ISS stage III (p = 0.0165). IL-10 serum or plasma concentration was significantly higher in Ps and MM patients when compared to HVs (p < 0.0001). Following the treatment with daratumumab the percentages of CD19+CD24hiCD38hi Bregs significantly decreased (p < 0.0003). Here, in the two opposite immune conditions, despite the differences in percentages of Bregs in Ps and MM we have identified some similarities in the IL-10 producing Bregs. Effective treatment of daratumumab besides the anti-myeloma effect was accompanied by the eradication of Bregs.
Highlights
The regulatory B cells (Bregs) are essential contributors to the pathogenesis of inflammatory and autoimmune conditions as well as a neoplastic disease [1].B regulatory (Breg) are known to mediate inflammation and maintain homeostasis and peripheral immune tolerance mainly via secretion of suppressive cytokines, such as interleukin-10(IL-10), interleukin-35 (IL-35), and the transforming growth factor-β (TGF-β), as well as via expression of inhibitory molecules, such as the programmed cell death ligand 1 (PDL1) [1,2]
CD19+CD24hiCD38hi Bregs Are Increased in Bone marrow mononuclear cells (BMMCs) of MM Patients, Whereas They Are
Flow cytometry was used to analyze the frequency of Bregs after short term cell cultures in Ps as well as MM patients
Summary
The regulatory B cells (Bregs) are essential contributors to the pathogenesis of inflammatory and autoimmune conditions as well as a neoplastic disease [1].Bregs are known to mediate inflammation and maintain homeostasis and peripheral immune tolerance mainly via secretion of suppressive cytokines, such as interleukin-10(IL-10), interleukin-35 (IL-35), and the transforming growth factor-β (TGF-β), as well as via expression of inhibitory molecules, such as the programmed cell death ligand 1 (PDL1) [1,2]. Bregs are known to mediate inflammation and maintain homeostasis and peripheral immune tolerance mainly via secretion of suppressive cytokines, such as interleukin-10. The level of IL-10 production by Bregs is indicative of their regulatory functions; the Bregs’ cell subsets producing IL-10, ranging from early immature transitional B cells (CD24hiCD38hi) to highly differentiated plasmablasts (CD27intCD38+) and plasma cells, are collectively referred to as the B10 cells [1,3,4]. T cells’ immunity and facilitation of their conversion into the regulatory T cells (Tregs), which is executed through the communication of CD40 on the Bregs’ surface with CD40L on the effector T cells, thereby leading to the T cells’ death and reduced response to the autoantigen [1]. Blair et al [3] found that within the peripheral blood of healthy individuals
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