Objective Assess the proportion of myeloid derived suppressor cells (MDSC), their expression of arginase-1 and PD-L1, and their relationship with the clinical phenotype of patients with idiopathic inflammatory myopathies (IIM). Methods We recruited 37 IIM adult patients and 10 healthy donors in Mexico City. We evaluated their clinical features, the proportion of MDSC and their expression of PD-L1 and arginase-1 by flow cytometry. Polymorphonuclear (PMN)-MDSC were defined as CD33int, CD11b+ and CD66b+ whilst monocytic (M)-MDSC were CD33+, CD11b+, HLA-DR- and CD14+. Serum cytokines were analyzed with a multiplex assay. We compared the quantitative variables with the Kruskal-Wallis and Mann–Whitney U tests and assessed correlations with Spearman Rho. Results Most patients had dermatomyositis (N = 30, 81.0%). IIM patients had a peripheral expansion of PMN-MDSC, and M-MDSC with an enhanced expression of arginase-1 and PD-L1. Patients with active disease had a decreased percentage (1.75% (0.31–5.50 vs 10.71 (3.16–15.58), p= 0.011) of M-MDSC, higher absolute number of PD-L1+ M-MDSC (23.21 cells/mm3 (11.16–148.9) vs 5.95 (4.66–102.7), p= 0.046) with increased expression of PD-L1 (3136 arbitrary units (2258–4992) vs 1961 (1885–2335), p= 0.038). PD-L1 expression in PMN-MDSC correlated with the visual analogue scale (VAS) of pulmonary disease activity (R = 0.34, p= 0.040), and damage (R = 0.36, p= 0.031), serum IL-5 (R = 0.55, p= 0.003), IL-6 (R = 0.46, p= 0.003), IL-8 (R = 0.53, p= 0.018), IL-10 (R = 0.48, p= 0.005) and GM-CSF (R = 0.48, p= 0.012). M-MDSC negatively correlated with the skeletal MITAX (R=-0.34, p= 0.038) and positively with IL-6 (R = 0.40, p= 0.045). Conclusion MDSC expressing arginase-1 and PD-L1 are expanded in IIM and correlate with disease activity, damage accrual and serum cytokines.

中文翻译：

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髓源性抑制细胞的外周扩张与炎症性肌病的疾病活动和损伤累积有关

目的 评估髓源性抑制细胞（MDSC）的比例、精氨酸酶-1和PD-L1的表达及其与特发性炎症性肌病（IIM）患者临床表型的关系。方法 我们在墨西哥城招募了 37 名 IIM 成年患者和 10 名健康供体。我们通过流式细胞术评估了他们的临床特征、MDSC 的比例以及他们的 PD-L1 和精氨酸酶-1 的表达。多形核 (PMN)-MDSC 被定义为 CD33int、CD11b+ 和 CD66b+，而单核细胞 (M)-MDSC 被定义为 CD33+、CD11b+、HLA-DR- 和 CD14+。用多重测定法分析血清细胞因子。我们将定量变量与 Kruskal-Wallis 和 Mann-Whitney U 检验进行了比较，并评估了与 Spearman Rho 的相关性。结果 大多数患者患有皮肌炎 (N = 30, 81.0%)。IIM 患者外周有 PMN-MDSC 和 M-MDSC 的扩张，精氨酸酶-1 和 PD-L1 的表达增强。活动性疾病患者的 M-MDSC 百分比下降（1.75%（0.31–5.50 vs 10.71 (3.16–15.58)，p= 0.011），PD-L1+ M-MDSC 的绝对数量较高（23.21 个细胞/mm3 (11.16–15.58) 148.9) 对比 5.95 (4.66–102.7)，p= 0.046) PD-L1 表达增加（3136 任意单位 (2258–4992) 对比 1961 (1885–2335)，p= 0.038）。PMN- 中的 PD-L1 表达MDSC 与肺部疾病活动（R = 0.34，p = 0.040）和损伤（R = 0.36，p = 0.031）、血清 IL-5（R = 0.55，p = 0.003）的视觉模拟量表（VAS）相关， IL-6（R = 0.46，p = 0.003），IL-8（R = 0.53，p = 0.018），IL-10（R = 0.48，p = 0.005）和 GM-CSF（R = 0.48，p = 0.012 ). M-MDSC 与骨骼 MITAX 呈负相关 (R=-0.34, p= 0.038)，与 IL-6 呈正相关 (R = 0.40, p = 0.045）。结论 表达精氨酸酶-1 和 PD-L1 的 MDSC 在 IIM 中扩增，并与疾病活动、损伤累积和血清细胞因子相关。