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全身型幼年特发性关节炎中淋巴细胞亚群、相关细胞因子、临床表型及预后的相关性

Associations of Lymphocyte Subpopulations, Related Cytokines, Clinical Phenotypes, and Outcomes in Systemic Juvenile Idiopathic Arthritis.

作者信息

Lerkvaleekul Butsabong, Sitthisarunkul Noppasorn, Apiwattanakul Nopporn, Klinmalai Chompunuch, Pongsakul Nutkridta, Vilaiyuk Soamarat

机构信息

Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

ACR Open Rheumatol. 2025 Aug;7(8):e70070. doi: 10.1002/acr2.70070.

DOI:10.1002/acr2.70070
PMID:40728052
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12305351/
Abstract

OBJECTIVE

To facilitate appropriate management, we aimed to evaluate associations between lymphocyte subsets and related cytokines with clinical characteristics and treatment outcomes of patients with systemic juvenile idiopathic arthritis (sJIA).

METHODS

We collected blood samples from 53 patients with sJIA and evaluated the percentages of lymphocyte subsets and cytokine levels. Patients were categorized into active (n = 18), persistent (n = 11), and inactive (n = 24) sJIA groups based on clinical phenotypes. Seventeen patients with active disease provided longitudinal blood samples at 0, 4 to 6, and 24 weeks. Among these patients, 12 patients were classified as sJIA treatment responders (sJIA-R) and 5 patients were classified as sJIA treatment nonresponders (sJIA-NR). The healthy control (HC) group comprised 32 age-matched children.

RESULTS

Dynamic changes in lymphocyte subsets and cytokine levels were observed over time. In the longitudinal cohort, patients in the sJIA-R group showed a significant decline in proinflammatory cytokines, including interleukin-1 (IL-1), interferon-γ (IFN-γ), monocyte chemoattractant protein-1, and IL-23, along with increases in CD3, CD4, and CD8 T cells. In contrast, patients in the sJIA-NR group had persistently elevated IL-1, IL-23, and tumor necrosis factor levels and natural killer (NK) T cell percentages. Despite clinical improvement, IL-18 and IFN-γ levels remained elevated compared to HCs throughout the 24-week follow-up. Analysis of minor lymphocyte subsets revealed low NK and gamma delta (γδ) T cell percentages during active disease and follow-up. Notably, IL-23 levels and γδ T cell percentages were significantly associated with several disease activity parameters.

CONCLUSION

Patients with sJIA exhibit altered lymphocyte subsets and inflammatory mediator production during the disease course, which may assist in identifying treatment responders and guiding therapeutic strategies. This study investigated associations of lymphocyte subpopulations, related cytokines, clinical phenotypes, and outcomes in systemic juvenile idiopathic (sJIA). Low percentages of NK and γδ-T cells were observed in patients with sJIA, particularly during active disease, compared to healthy controls. Persistent elevations in IL-1, IL-23, TNF, and NK T cell percentage were associated with poor treatment response.

摘要

目的

为促进合理管理,我们旨在评估淋巴细胞亚群和相关细胞因子与全身型幼年特发性关节炎(sJIA)患者的临床特征及治疗结果之间的关联。

方法

我们收集了53例sJIA患者的血样,评估淋巴细胞亚群的百分比和细胞因子水平。根据临床表型将患者分为活动期(n = 18)、持续期(n = 11)和非活动期(n = 24)sJIA组。17例活动期疾病患者在第0、4至6周和24周提供了纵向血样。在这些患者中,12例患者被分类为sJIA治疗反应者(sJIA-R),5例患者被分类为sJIA治疗无反应者(sJIA-NR)。健康对照组(HC)由32名年龄匹配的儿童组成。

结果

观察到淋巴细胞亚群和细胞因子水平随时间的动态变化。在纵向队列中,sJIA-R组患者的促炎细胞因子,包括白细胞介素-1(IL-1)、干扰素-γ(IFN-γ)、单核细胞趋化蛋白-1和IL-23显著下降,同时CD3、CD4和CD8 T细胞增加。相比之下,sJIA-NR组患者的IL-1、IL-23和肿瘤坏死因子水平以及自然杀伤(NK)T细胞百分比持续升高。尽管临床症状有所改善,但在整个24周的随访中,与健康对照组相比,IL-18和IFN-γ水平仍保持升高。对次要淋巴细胞亚群的分析显示,在活动期疾病和随访期间,NK和γδ T细胞百分比低。值得注意的是,IL-23水平和γδ T细胞百分比与几个疾病活动参数显著相关。

结论

sJIA患者在疾病过程中表现出淋巴细胞亚群和炎症介质产生的改变,这可能有助于识别治疗反应者并指导治疗策略。本研究调查了全身型幼年特发性关节炎(sJIA)中淋巴细胞亚群、相关细胞因子、临床表型和结果之间的关联。与健康对照组相比,sJIA患者中NK和γδ-T细胞百分比低,尤其是在活动期疾病期间。IL-1、IL-23、TNF和NK T细胞百分比持续升高与治疗反应不佳相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/b84aa07b64de/ACR2-7-e70070-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/1fea0c8c72af/ACR2-7-e70070-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/c7372e47b316/ACR2-7-e70070-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/34769fb340d5/ACR2-7-e70070-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/b84aa07b64de/ACR2-7-e70070-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/1fea0c8c72af/ACR2-7-e70070-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/6c1e80b108a6/ACR2-7-e70070-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/c7372e47b316/ACR2-7-e70070-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/990e2d181556/ACR2-7-e70070-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/34769fb340d5/ACR2-7-e70070-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5462/12305351/b84aa07b64de/ACR2-7-e70070-g005.jpg

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