{"title":"儿童期系统性红斑狼疮患者CD4+中枢记忆T细胞水平及其临床相关性","authors":"Feng-Qiao Gao, Xiao-Zhen Zhao, Shi-Peng Li, Chao Li, Jiang-Hong Deng, Jun-Mei Zhang, Xiao-Hua Tan, Xuan-Yi Liu, Cai-Feng Li","doi":"10.1177/09612033251366398","DOIUrl":null,"url":null,"abstract":"<p><p>ObjectivesThis study aims to investigate CD4<sup>+</sup> central memory T cells (CD4<sup>+</sup> TCM) levels in childhood-onset systemic lupus erythematosus (cSLE) and their association with disease activity, clinical features, and treatment responses.MethodsA total of 202 children with newly diagnosed, untreated rheumatic diseases were recruited, comprising 64 cases of cSLE, 71 cases of juvenile idiopathic arthritis, 31 cases of juvenile dermatomyositis, 36 cases of autoinflammatory diseases, and 22 healthy controls. Lymphocyte subsets were analyzed using multi-color flow cytometry, and clinical data and laboratory test results were collected. The correlation between CD4<sup>+</sup> TCM levels and SLEDAI scores, clinical manifestations, autoantibodies, and kidney injury markers was examined. Subsequently, 21 cSLE patients underwent follow-up assessments and retesting post-treatment.ResultsThe proportion of CD4<sup>+</sup> TCM (44.3 ± 11.5%) in cSLE was significantly higher compared to those with other pediatric rheumatic diseases (<i>p</i> < .05). A negative correlation was observed between the level of CD4<sup>+</sup> TCM and the SLEDAI-2000 score (r = -0.255, <i>p</i> = .021), indicating that higher disease activity was associated with lower CD4<sup>+</sup> TCM levels. Furthermore, CD4<sup>+</sup> TCM levels were negatively correlated with oral ulcers (r = -0.285, <i>p</i> = .011) and positively correlated with leukopenia (r = 0.302, <i>p</i> = .008). In terms of laboratory indicators, CD4<sup>+</sup> TCM showed negative correlations with anti-dsDNA antibodies (r = -0.294, <i>p</i> = .009) and anti-histone antibodies (r = -0.232, <i>p</i> = .033), while exhibiting a positive correlation with anti-Sm antibodies (r = 0.245, <i>p</i> = .025). Additionally, CD4<sup>+</sup> TCM demonstrated significant negative correlations with early renal injury markers, urinary transferrin (r = -0.315, <i>p</i> = .008), and urinary microalbumin (r = -0.284, <i>p</i> = .015). CD4<sup>+</sup> TCM was strongly negatively correlated with CD4<sup>+</sup> Naive cells (r = -0.831, <i>p</i> < .001), positively correlated with other memory cell subsets, and negatively correlated with IFN-α levels (r = -0.364, <i>p</i> = .031). Longitudinal analysis revealed a time-dependent biphasic pattern in CD4<sup>+</sup> TCM levels. Cyclophosphamide-treated patients showed significantly increased CD4<sup>+</sup> TCM levels compared to non-cyclophosphamide groups (<i>p</i> = .034).ConclusionsCD4<sup>+</sup> TCM likely plays a central immune regulatory role in cSLE, with its levels closely associated with disease activity, specific autoantibody production, and early organ damage. Post-treatment changes in CD4<sup>+</sup> TCM levels may indicate therapeutic efficacy and suggest their potential as biomarkers, offering a fresh perspective on immune memory regulation in cSLE and exploring novel treatment approaches.</p>","PeriodicalId":18044,"journal":{"name":"Lupus","volume":" ","pages":"1166-1177"},"PeriodicalIF":1.9000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Level of CD4<sup>+</sup> central memory T cells and its clinical correlation in childhood-onset systemic lupus erythematosus.\",\"authors\":\"Feng-Qiao Gao, Xiao-Zhen Zhao, Shi-Peng Li, Chao Li, Jiang-Hong Deng, Jun-Mei Zhang, Xiao-Hua Tan, Xuan-Yi Liu, Cai-Feng Li\",\"doi\":\"10.1177/09612033251366398\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>ObjectivesThis study aims to investigate CD4<sup>+</sup> central memory T cells (CD4<sup>+</sup> TCM) levels in childhood-onset systemic lupus erythematosus (cSLE) and their association with disease activity, clinical features, and treatment responses.MethodsA total of 202 children with newly diagnosed, untreated rheumatic diseases were recruited, comprising 64 cases of cSLE, 71 cases of juvenile idiopathic arthritis, 31 cases of juvenile dermatomyositis, 36 cases of autoinflammatory diseases, and 22 healthy controls. Lymphocyte subsets were analyzed using multi-color flow cytometry, and clinical data and laboratory test results were collected. The correlation between CD4<sup>+</sup> TCM levels and SLEDAI scores, clinical manifestations, autoantibodies, and kidney injury markers was examined. Subsequently, 21 cSLE patients underwent follow-up assessments and retesting post-treatment.ResultsThe proportion of CD4<sup>+</sup> TCM (44.3 ± 11.5%) in cSLE was significantly higher compared to those with other pediatric rheumatic diseases (<i>p</i> < .05). A negative correlation was observed between the level of CD4<sup>+</sup> TCM and the SLEDAI-2000 score (r = -0.255, <i>p</i> = .021), indicating that higher disease activity was associated with lower CD4<sup>+</sup> TCM levels. Furthermore, CD4<sup>+</sup> TCM levels were negatively correlated with oral ulcers (r = -0.285, <i>p</i> = .011) and positively correlated with leukopenia (r = 0.302, <i>p</i> = .008). In terms of laboratory indicators, CD4<sup>+</sup> TCM showed negative correlations with anti-dsDNA antibodies (r = -0.294, <i>p</i> = .009) and anti-histone antibodies (r = -0.232, <i>p</i> = .033), while exhibiting a positive correlation with anti-Sm antibodies (r = 0.245, <i>p</i> = .025). Additionally, CD4<sup>+</sup> TCM demonstrated significant negative correlations with early renal injury markers, urinary transferrin (r = -0.315, <i>p</i> = .008), and urinary microalbumin (r = -0.284, <i>p</i> = .015). CD4<sup>+</sup> TCM was strongly negatively correlated with CD4<sup>+</sup> Naive cells (r = -0.831, <i>p</i> < .001), positively correlated with other memory cell subsets, and negatively correlated with IFN-α levels (r = -0.364, <i>p</i> = .031). Longitudinal analysis revealed a time-dependent biphasic pattern in CD4<sup>+</sup> TCM levels. Cyclophosphamide-treated patients showed significantly increased CD4<sup>+</sup> TCM levels compared to non-cyclophosphamide groups (<i>p</i> = .034).ConclusionsCD4<sup>+</sup> TCM likely plays a central immune regulatory role in cSLE, with its levels closely associated with disease activity, specific autoantibody production, and early organ damage. Post-treatment changes in CD4<sup>+</sup> TCM levels may indicate therapeutic efficacy and suggest their potential as biomarkers, offering a fresh perspective on immune memory regulation in cSLE and exploring novel treatment approaches.</p>\",\"PeriodicalId\":18044,\"journal\":{\"name\":\"Lupus\",\"volume\":\" \",\"pages\":\"1166-1177\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2025-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lupus\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/09612033251366398\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/4 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"RHEUMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lupus","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/09612033251366398","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/4 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的探讨儿童期系统性红斑狼疮(cSLE)患者CD4+中枢记忆T细胞(CD4+ TCM)水平及其与疾病活动性、临床特征和治疗反应的关系。方法纳入202例新诊断、未经治疗的风湿病患儿,其中慢性风湿性关节炎64例,幼年特发性关节炎71例,幼年皮肌炎31例,自身炎症性疾病36例,健康对照22例。采用多色流式细胞术分析淋巴细胞亚群,收集临床资料和实验室检测结果。检测CD4+ TCM水平与SLEDAI评分、临床表现、自身抗体及肾损伤标志物的相关性。随后,21例cSLE患者接受了随访评估和治疗后复查。结果cle患儿CD4+中医比例(44.3±11.5%)明显高于其他儿童风湿疾病(p < 0.05)。CD4+ TCM水平与SLEDAI-2000评分呈负相关(r = -0.255, p = 0.021),表明疾病活动度越高,CD4+ TCM水平越低。CD4+ TCM水平与口腔溃疡呈负相关(r = -0.285, p = 0.011),与白细胞减少呈正相关(r = 0.302, p = 0.008)。在实验室指标方面,CD4+ TCM与抗dsdna抗体(r = -0.294, p = 0.009)、抗组蛋白抗体(r = -0.232, p = 0.033)呈负相关,与抗sm抗体呈正相关(r = 0.245, p = 0.025)。此外,CD4+ TCM与早期肾损伤标志物、尿转铁蛋白(r = -0.315, p = 0.008)、尿微量白蛋白(r = -0.284, p = 0.015)呈显著负相关。CD4+ TCM与CD4+ Naive细胞呈强负相关(r = -0.831, p < 0.001),与其他记忆细胞亚群呈正相关,与IFN-α水平呈负相关(r = -0.364, p = 0.031)。纵向分析显示CD4+ TCM水平具有时间依赖性的双相模式。与非环磷酰胺组相比,环磷酰胺组患者CD4+ TCM水平显著升高(p = 0.034)。结论scd4 +中药可能在cSLE中发挥核心免疫调节作用,其水平与疾病活动性、特异性自身抗体产生和早期器官损伤密切相关。治疗后CD4+中医水平的变化可能表明治疗效果,并提示其作为生物标志物的潜力,为cSLE免疫记忆调节提供新的视角,探索新的治疗方法。
Level of CD4+ central memory T cells and its clinical correlation in childhood-onset systemic lupus erythematosus.
ObjectivesThis study aims to investigate CD4+ central memory T cells (CD4+ TCM) levels in childhood-onset systemic lupus erythematosus (cSLE) and their association with disease activity, clinical features, and treatment responses.MethodsA total of 202 children with newly diagnosed, untreated rheumatic diseases were recruited, comprising 64 cases of cSLE, 71 cases of juvenile idiopathic arthritis, 31 cases of juvenile dermatomyositis, 36 cases of autoinflammatory diseases, and 22 healthy controls. Lymphocyte subsets were analyzed using multi-color flow cytometry, and clinical data and laboratory test results were collected. The correlation between CD4+ TCM levels and SLEDAI scores, clinical manifestations, autoantibodies, and kidney injury markers was examined. Subsequently, 21 cSLE patients underwent follow-up assessments and retesting post-treatment.ResultsThe proportion of CD4+ TCM (44.3 ± 11.5%) in cSLE was significantly higher compared to those with other pediatric rheumatic diseases (p < .05). A negative correlation was observed between the level of CD4+ TCM and the SLEDAI-2000 score (r = -0.255, p = .021), indicating that higher disease activity was associated with lower CD4+ TCM levels. Furthermore, CD4+ TCM levels were negatively correlated with oral ulcers (r = -0.285, p = .011) and positively correlated with leukopenia (r = 0.302, p = .008). In terms of laboratory indicators, CD4+ TCM showed negative correlations with anti-dsDNA antibodies (r = -0.294, p = .009) and anti-histone antibodies (r = -0.232, p = .033), while exhibiting a positive correlation with anti-Sm antibodies (r = 0.245, p = .025). Additionally, CD4+ TCM demonstrated significant negative correlations with early renal injury markers, urinary transferrin (r = -0.315, p = .008), and urinary microalbumin (r = -0.284, p = .015). CD4+ TCM was strongly negatively correlated with CD4+ Naive cells (r = -0.831, p < .001), positively correlated with other memory cell subsets, and negatively correlated with IFN-α levels (r = -0.364, p = .031). Longitudinal analysis revealed a time-dependent biphasic pattern in CD4+ TCM levels. Cyclophosphamide-treated patients showed significantly increased CD4+ TCM levels compared to non-cyclophosphamide groups (p = .034).ConclusionsCD4+ TCM likely plays a central immune regulatory role in cSLE, with its levels closely associated with disease activity, specific autoantibody production, and early organ damage. Post-treatment changes in CD4+ TCM levels may indicate therapeutic efficacy and suggest their potential as biomarkers, offering a fresh perspective on immune memory regulation in cSLE and exploring novel treatment approaches.
期刊介绍:
The only fully peer reviewed international journal devoted exclusively to lupus (and related disease) research. Lupus includes the most promising new clinical and laboratory-based studies from leading specialists in all lupus-related disciplines. Invaluable reading, with extended coverage, lupus-related disciplines include: Rheumatology, Dermatology, Immunology, Obstetrics, Psychiatry and Cardiovascular Research…