Yu Hanjie, Wang Ling, Qin Ling, Yu Hanqing, Hu Ran, Jia Zhenghu, Bao Hui, Wang Haichao, Xue Wen, Song Yaxiang, Yin Zhinan, Peng Ai
Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
Front Immunol. 2025 Apr 17;16:1540429. doi: 10.3389/fimmu.2025.1540429. eCollection 2025.
Lymphocytes and their subsets are implicated in both the onset and remission of gout. However, the specific roles in gout recurrence and complete remission remain unclear. This study aimed to characterize lymphocyte immunophenotypes across different stages of gout and developed a predictive model for remission and recurrence of gout.
Plasma levels of 75 lymphocyte immunophenotypes were determined using multiplex flow cytometry in patients with acute gout flare (AG, n=78), gout remission (RG, n=63), and healthy controls (NC, n=66). Lymphocyte immunophenotyping candidates and significant clinical parameters were subjected to LASSO regression for conducting a predictive model.
Significant variations in lymphocyte profiles were identified among the groups. A combination of T peripheral helper cells, virus-specific cytotoxic natural killer (NK) cells, inhibition of Vδ1 and Vδ2 cells, along with BMI, eGFR, hemoglobin, uric acid, distinguished RG from NC (AUC=0.934). Similarly, inhibition of Vδ2 cells, virus-specific cytotoxic NK cells, inactive and terminally differentiated virus-specific CD8 T cells, plus hematological parameters, classified RG from AG (AUC = 0.814) and predicted gout recurrence in a one-year follow-up validation cohort (AUC = 0.724). Inhibition of Vδ2 cells and virus-infected specific cytotoxic NK cells are strongly associated with gout recurrence and complete remission.
Significant alterations in lymphocyte immunophenotypes, notably the inhibition of Vδ2 cells and virus-infected specific cytotoxic NK cells during the transition from gout recurrence to complete remission, provide compelling evidence to enhance the clinical delineation of gout stages and propel mechanistic investigations into the progression of gout.
淋巴细胞及其亚群与痛风的发作和缓解均有关联。然而，它们在痛风复发和完全缓解中的具体作用仍不明确。本研究旨在描绘痛风不同阶段的淋巴细胞免疫表型特征，并建立痛风缓解和复发的预测模型。
采用多重流式细胞术测定急性痛风发作患者（AG，n = 78）、痛风缓解患者（RG，n = 63）和健康对照者（NC，n = 66）血浆中75种淋巴细胞免疫表型的水平。对淋巴细胞免疫表型候选指标和重要临床参数进行LASSO回归以构建预测模型。
各组间淋巴细胞谱存在显著差异。外周辅助性T细胞、病毒特异性细胞毒性自然杀伤（NK）细胞、Vδ1和Vδ2细胞的抑制，以及BMI、估算肾小球滤过率（eGFR）、血红蛋白、尿酸的组合，可将RG与NC区分开来（AUC = 0.934）。同样，Vδ2细胞的抑制、病毒特异性细胞毒性NK细胞、无活性和终末分化的病毒特异性CD8 T细胞，加上血液学参数，可将RG与AG区分开来（AUC = 0.814），并在一年随访验证队列中预测痛风复发（AUC = 0.724）。Vδ2细胞的抑制和病毒感染特异性细胞毒性NK细胞与痛风复发和完全缓解密切相关。
淋巴细胞免疫表型的显著改变，尤其是在从痛风复发到完全缓解的转变过程中Vδ2细胞和病毒感染特异性细胞毒性NK细胞的抑制，为加强痛风阶段的临床界定和推动痛风进展的机制研究提供了有力证据。
