Research Laboratory, Division of Pediatric Infectious Diseases, Department of Pediatrics, 28105Universidade Federal de São Paulo, São Paulo, Brazil.
Unit of Pediatric Rheumatology, Department of Pediatrics, 28105Universidade Federal de São Paulo, São Paulo, Brazil.
Lupus. 2022 Sep;31(10):1237-1244. doi: 10.1177/09612033221112809. Epub 2022 Jul 18.
Juvenile systemic lupus erythematosus (jSLE) is known to be more severe and with a higher frequency of renal and central nervous system impairment when compared to systemic lupus erythematosus in adults. The study of immunological characteristics of jSLE patients might help to envisage better treatment strategies to reduce the burden of the disease.
To characterize peripheral lymphocytes, assessing activation markers, and PD-1 expression on T cells; to evaluate in vitro cytokine expression upon stimulation in jSLE patients and age-matched controls.
Eighteen jSLE patients on low disease activity and 25 matched healthy adolescents were evaluated for immune activation and PD-1 expression on peripheral blood lymphocytes by flow cytometry. Twenty-one cytokines were assessed by X-MAP technology after in vitro stimulation of peripheral blood with phytohemagglutinin.
jSLE patients had lower numbers of CD4 T, CD8 T, B, and NK cells; higher central memory CD8 T cell percentages were noted in jSLE adolescents in comparison with controls ( = 0.014). B cells subsets showed a higher percentage of exhausted memory subset than controls ( = 0.014). The expression of PD-1 on CD4 T and CD8 T cells did not show relevant changes in jSLE adolescents. After stimulation of peripheral blood, cell supernatant of jSLE patients showed a trend to lower concentrations of IL-10 (=0.080) and higher concentrations of IL-23 ( = 0.063) than controls.
jSLE patients on low disease activity maintain lymphopenia of all subsets, with a B cell profile of exhaustion. Upon in vitro stimulation, peripheral blood cell supernatant showed a shift to IL-23, suggesting a role of inhibitors of this cytokine as another potential therapeutic target for those patients.
与成人系统性红斑狼疮（SLE）相比，幼年系统性红斑狼疮（jSLE）的病情更为严重，且更常伴有肾脏和中枢神经系统损害。研究 jSLE 患者的免疫学特征可能有助于设想更好的治疗策略，以减轻疾病负担。
描述 jSLE 患者外周血淋巴细胞的特征，评估其 T 细胞的激活标志物和 PD-1 表达；评估 jSLE 患者和年龄匹配的健康对照者体外刺激后的细胞因子表达情况。
通过流式细胞术评估 18 例处于低疾病活动度的 jSLE 患者和 25 名匹配的健康青少年的外周血淋巴细胞的免疫激活和 PD-1 表达情况。通过 X-MAP 技术评估植物血凝素体外刺激外周血后 21 种细胞因子的表达情况。
jSLE 患者的 CD4 T、CD8 T、B 和 NK 细胞数量较低；与对照组相比，jSLE 青少年的中央记忆 CD8 T 细胞百分比更高（ = 0.014）。B 细胞亚群中耗尽的记忆亚群比例高于对照组（ = 0.014）。jSLE 青少年的 CD4 T 和 CD8 T 细胞上 PD-1 的表达没有明显变化。外周血刺激后，jSLE 患者的细胞上清液中 IL-10 的浓度呈下降趋势（ = 0.080），IL-23 的浓度呈上升趋势（ = 0.063），高于对照组。
处于低疾病活动度的 jSLE 患者仍存在所有亚群的淋巴细胞减少，B 细胞表现为耗竭状态。体外刺激后，外周血细胞上清液中出现向 IL-23 的转移，这表明抑制这种细胞因子可能成为这些患者的另一个潜在治疗靶点。
