Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE.
Dysregulated CD38 Expression on Peripheral Blood Immune Cell Subsets in SLE.
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DOI：
10.3390/ijms22052424
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发表时间：
2021-02-28
影响因子：
5.6
通讯作者：
Alexander T
中科院分区：
文献类型：
--
作者：
Burns M;Ostendorf L;Biesen R;Grützkau A;Hiepe F;Mei HE;Alexander T
鉴于CD38在浆细胞上的一致高表达，CD38被认为是系统性红斑狼疮（SLE）患者的治疗靶点。在此，我们研究了CD38在外周血白细胞谱系中的表达分布，以评估CD38靶向抗体对这些免疫细胞亚群的潜在治疗效果，并描述了CD38作为SLE生物标志物的用途。我们通过流式细胞术和质量细胞术分析了两个不同队列中CD38在外周血白细胞亚群上的表达，共包括56例SLE患者。CD38表达水平随后在免疫细胞系和亚群之间以及与SLE的临床和血清学疾病参数相关。与健康对照（HC）相比，SLE患者循环浆细胞样树突状细胞、CD14++CD16+单核细胞、CD56+ CD16dim自然杀伤细胞、边缘区样IgD+CD27+ B细胞以及CD4+和CD8+记忆T细胞中的CD38表达水平显著升高。相关分析显示SLE患者个体先天T细胞亚群和记忆T细胞亚群协调表达CD38，而HC患者不协调表达CD38。然而，不同患者的CD38表达水平存在差异，免疫细胞亚群的CD38表达与疾病活动性指数SLEDAI-2K或已建立的疾病活动性血清学和免疫学标志物之间没有相关性。总之，我们确定了SLE免疫细胞CD38表达的广泛变化，在个体患者中不同白细胞亚群之间高度相关，但在SLE患者群体中是异质性的，无论疾病严重程度或临床表现如何。随着抗cd38治疗在SLE中的研究，我们的结果可能对抗cd38单克隆抗体靶向致病性白细胞具有重要意义。
Given its uniformly high expression on plasma cells, CD38 has been considered as a therapeutic target in patients with systemic lupus erythematosus (SLE). Herein, we investigate the distribution of CD38 expression by peripheral blood leukocyte lineages to evaluate the potential therapeutic effect of CD38-targeting antibodies on these immune cell subsets and to delineate the use of CD38 as a biomarker in SLE. We analyzed the expression of CD38 on peripheral blood leukocyte subsets by flow and mass cytometry in two different cohorts, comprising a total of 56 SLE patients. The CD38 expression levels were subsequently correlated across immune cell lineages and subsets, and with clinical and serologic disease parameters of SLE. Compared to healthy controls (HC), CD38 expression levels in SLE were significantly increased on circulating plasmacytoid dendritic cells, CD14++CD16+ monocytes, CD56+ CD16dim natural killer cells, marginal zone-like IgD+CD27+ B cells, and on CD4+ and CD8+ memory T cells. Correlation analyses revealed coordinated CD38 expression between individual innate and memory T cell subsets in SLE but not HC. However, CD38 expression levels were heterogeneous across patients, and no correlation was found between CD38 expression on immune cell subsets and the disease activity index SLEDAI-2K or established serologic and immunological markers of disease activity. In conclusion, we identified widespread changes in CD38 expression on SLE immune cells that highly correlated over different leukocyte subsets within individual patients, but was heterogenous within the population of SLE patients, regardless of disease severity or clinical manifestations. As anti-CD38 treatment is being investigated in SLE, our results may have important implications for the personalized targeting of pathogenic leukocytes by anti-CD38 monoclonal antibodies.
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影响因子：
16.6
作者：
Belkina, Anna C.;Ciccolella, Christopher O.;Snyder-Cappione, Jennifer E.
通讯作者：
Snyder-Cappione, Jennifer E.
影响因子：
--
作者：
Nowicka, Malgorzata;Krieg, Carsten;Robinson, Mark D
通讯作者：
Robinson, Mark D
影响因子：
8.8
作者：
Katsuyama E;Suarez-Fueyo A;Bradley SJ;Mizui M;Marin AV;Mulki L;Krishfield S;Malavasi F;Yoon J;Sui SJH;Kyttaris VC;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
4.9
作者：
Cole S;Walsh A;Yin X;Wechalekar MD;Smith MD;Proudman SM;Veale DJ;Fearon U;Pitzalis C;Humby F;Bombardieri M;Axel A;Adams H 3rd;Chiu C;Sharp M;Alvarez J;Anderson I;Madakamutil L;Nagpal S;Guo Y
通讯作者：
Guo Y
影响因子：
13.3
作者：
Aringer, Martin;Costenbader, Karen;Johnson, Sindhu R.
通讯作者：
Johnson, Sindhu R.