Department of Cosmetology and Aestetic Medicine, Medical University of Lublin, 20-093 Lublin, Poland.
Experimental Hematooncology Department, Medical University of Lublin, 20-093 Lublin, Poland.
Cells. 2021 Feb 16;10(2):411. doi: 10.3390/cells10020411.
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 ( < 0.0001). The percentage of CD19+CD24hiCD38hi Bregs was significantly higher in MM patients with the ISS stage I ( = 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 ( < 0.0001). Following the treatment with daratumumab the percentages of CD19+CD24hiCD38hi Bregs significantly decreased ( < 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.
银屑病（Ps）是一种自身免疫性疾病，多发性骨髓瘤（MM）是一种血液肿瘤，其特征是效应细胞和调节细胞之间失衡导致免疫失调，包括 B 调节性（Breg）淋巴细胞。本研究使用了 80 例银屑病患者、17 例接受达雷妥尤单抗（抗 CD38 单克隆抗体）治疗前后复发/难治性 MM 患者、23 名健康志愿者（HV）和 59 例 MM 患者的骨髓样本。通过流式细胞术使用 CD19、CD24 和 CD38 来确定 Breg。通过流式细胞术在 CD40L、LPS 和 CpG 刺激后评估白细胞介素-10（IL-10）的细胞内产生。使用 ELISA 方法测试 IL-10 血清或血浆浓度。与 HV 相比，Ps 患者的 CD19+CD24hiCD38hi Breg 百分比没有差异，而 Breg 中 IL-10 的产生明显更高。与 HV 相比，MM 患者的 CD19+CD24hiCD38hi Breg 百分比明显更高（<0.0001）。ISS 分期 I 的 MM 患者的 CD19+CD24hiCD38hi Breg 百分比明显更高（=0.0233），而 Breg 中 IL-10 的产生在 ISS 分期 III 时明显更高（p=0.0165）。与 HV 相比，Ps 和 MM 患者的 IL-10 血清或血浆浓度明显更高（<0.0001）。达雷妥尤单抗治疗后，CD19+CD24hiCD38hi Breg 的百分比明显降低（<0.0003）。在这里，在两种相反的免疫条件下，尽管 Ps 和 MM 中的 Breg 百分比存在差异，但我们发现了一些产生 IL-10 的 Breg 之间的相似之处。达雷妥尤单抗的有效治疗除了抗骨髓瘤作用外，还伴随着 Breg 的消除。
