Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.
Clin Exp Med. 2023 Nov;23(7):3605-3617. doi: 10.1007/s10238-023-01155-5. Epub 2023 Aug 2.
Dermatomyositis (DM) represents a multifaceted chronic inflammatory myopathy, primarily manifesting as progressive deterioration of muscular and cutaneous tissues. Despite an incomplete comprehension of DM's etiology and pathogenesis, current evidence implicates the involvement of T lymphocyte infiltration, extensive cytokine release, myositis-specific antibodies, and myositis-associated antibodies in disease development. Serum soluble interleukin-2 receptor (sIL-2R) frequently serves as a marker for T cell activation; however, its role remains elusive. Consequently, this investigation sought to elucidate the association between sIL-2R levels, peripheral blood lymphocyte subset counts, and related cytokines in DM patients, with the aim of uncovering the intricate mechanisms underlying DM and establishing a theoretical foundation for the implementation of precise, targeted, individualized immunomodulatory therapy. In this study, a cohort of 60 dermatomyositis (DM) patients, comprising 32 with inactive DM and 28 with active DM, was enrolled and stratified into inactive and active groups based on the Myositis Disease Activity Visual Analogue Scale (MYOACT). Flow cytometry was employed to quantify the absolute counts of peripheral lymphocyte subsets and CD4+T cell subsets in each group, while a flow cytometry bead array was utilized to measure serum cytokine levels. In a comparative analysis between healthy individuals and patients diagnosed with DM, we observed a marked elevation in serum sIL-2R concentrations (P < 0.001) and T-helper 17 cell/regulatory T cell (Th17/Treg) ratios (P < 0.01) within the latter group. A positive correlation was identified between serum sIL-2R levels and various parameters, including ESR, CRP, VAS, AST, CKMB, LDH, HBDH, PT, APTT, DDi, IL-6, IL-10, and IFN-γlevels (P < 0.05). In contrast, serum sIL-2R levels demonstrated a negative correlation with LY, HGB, ALB, Th17 cell populations, and Th17/Treg cell ratios (P < 0.05). Employing multivariate logistic regression, we identified serum sIL-2R concentrations as an independent risk factor for both disease activity and hepatic involvement in DM patients. Moreover, receiver operating characteristic (ROC) curve analyses revealed that serum sIL-2R levels significantly contributed to the differentiation of disease activity and the detection of liver involvement in DM patients, with areas under the ROC curve (AUC) of 0.757 (95% CI 0.630-0.884, P = 0.001) and 0.826 (95% CI 0.717-0.935, P < 0.001), respectively. This study highlights the potential utility of serum sIL-2R levels as a valuable biomarker for assessing disease activity and liver involvement in dermatomyositis. Elevated serum concentrations of sIL-2R were observed in patients with DM, exhibiting significant associations with Th17 cell populations and Th17/ Treg ratios. These findings indicate that sIL-2R may be implicated in the immunopathogenesis of DM, thereby warranting further investigation to elucidate its role in the disease process.
皮肌炎(DM)是一种多方面的慢性炎症性肌病,主要表现为肌肉和皮肤组织的进行性恶化。尽管人们对 DM 的病因和发病机制还不完全了解,但目前的证据表明 T 淋巴细胞浸润、广泛的细胞因子释放、肌炎特异性抗体和肌炎相关抗体参与了疾病的发展。血清可溶性白细胞介素-2 受体(sIL-2R)通常作为 T 细胞活化的标志物;然而,其作用仍不清楚。因此,本研究旨在探讨 DM 患者血清 sIL-2R 水平、外周血淋巴细胞亚群计数及相关细胞因子之间的关系,以期揭示 DM 的复杂发病机制,为实施精确、靶向、个体化免疫调节治疗提供理论依据。本研究纳入了 60 例皮肌炎(DM)患者,其中 32 例为无活动 DM 患者,28 例为活动 DM 患者。根据肌炎疾病活动视觉模拟量表(MYOACT)将患者分为无活动组和活动组。采用流式细胞术检测各组外周血淋巴细胞亚群和 CD4+T 细胞亚群的绝对计数,采用流式细胞术微珠阵列检测血清细胞因子水平。在健康对照者与 DM 患者的比较分析中,我们发现后者血清 sIL-2R 浓度显著升高(P<0.001),Th17/Treg 比值升高(P<0.01)。血清 sIL-2R 水平与 ESR、CRP、VAS、AST、CKMB、LDH、HBDH、PT、APTT、DDi、IL-6、IL-10 和 IFN-γ水平等参数呈正相关(P<0.05)。相反,血清 sIL-2R 水平与 LY、HGB、ALB、Th17 细胞群和 Th17/Treg 细胞比值呈负相关(P<0.05)。采用多变量 logistic 回归分析,我们发现血清 sIL-2R 浓度是 DM 患者疾病活动度和肝受累的独立危险因素。此外,受试者工作特征(ROC)曲线分析显示,血清 sIL-2R 水平对 DM 患者疾病活动度的区分和肝受累的检测具有显著意义,ROC 曲线下面积(AUC)分别为 0.757(95%CI 0.630-0.884,P=0.001)和 0.826(95%CI 0.717-0.935,P<0.001)。本研究表明,血清 sIL-2R 水平可作为评估皮肌炎疾病活动度和肝受累的有价值的生物标志物。DM 患者血清 sIL-2R 浓度升高,与 Th17 细胞群和 Th17/Treg 比值呈显著相关。这些发现表明 sIL-2R 可能参与 DM 的免疫发病机制,因此需要进一步研究其在疾病过程中的作用。