Zhao Ping, Song Saizhe, Cheng Wei, Peng Cheng, Wang Junrong, Chang Xin, Wu Jian, Hu Zhongli, Liu Cuiping
Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-Related Diseases, Bengbu, China.
Clin Rheumatol. 2025 Sep 4. doi: 10.1007/s10067-025-07665-9.
We aimed to explore the expression and clinical significance of TIGITCD56NK cells within the peripheral blood of patients with primary Sjögren's syndrome (pSS) in this study, as well as to examine the role of TIGIT in modulating NK cell function in individuals with pSS.
The percentage of TIGITCD56NK cells was detected in the peripheral blood of 76 individuals with pSS and 63 healthy controls (HCs) using flow cytometry. The percentage of TIGITCD56NK cells across various clinical features, laboratory parameters, and between active and inactive patients was analyzed. Subsequently, we analyzed the relativity between the percentage of TIGITCD56NK cells and the clinical parameters in pSS patients. The percentage of TIGITCD56NK cells in 10 patients with pSS was observed before and after treatment. Furthermore, we constructed receiver operating characteristic (ROC) curves to assess the diagnostic value of the percentage of TIGITCD56NK cells in pSS and to predict the disease activity of pSS. We further detected the levels of cytokines secreted by TIGIT and TIGITNK cells in 5 pSS patients to assess the function of NK cells.
In patients with pSS, there was a reduction in the percentage of TIGITCD56NK cells, particularly among those with active disease. The percentage of TIGITCD56NK cells exhibited a significant reduction in patients with pSS accompanying xerostomia, decayed tooth, glandular swelling, fatigue, arthralgia, cutaneous manifestations, renal tubular acidosis (RTA), interstitial lung disease (ILD), leukopenia, lymphopenia, increased serum globulin, increased ESR, increased IgG, increased IgA, and positive tests for anti-Ro52, anti-Ro60, and rheumatoid factor (RF), compared to those with negative results. TIGIT expression on CD56 NK cells exhibited a negative relevance with ESR, serum globulin levels, RF, IgG levels, ESSDAI scores, and ESSPRI scores. After treatment, the TIGITCD56NK cells percentage increased notably. The ROC curve demonstrated that the level of TIGITCD56NK cell percentage exhibited an excellent capacity for differentiating pSS and predicting disease activity. The expression levels of CD69, Ki67, perforin, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were found to be lower in TIGITCD56NK cells compared to TIGITCD56NK cells among patients with pSS. Furthermore, we discovered that expression levels of perforin and TNF-α were negatively related with that of TIGITCD56NK cells.
Our research indicated that a reduction in TIGITCD56NK cell percentage was related with clinical characteristics, laboratory indicators, disease progression, and outcome prediction in patients with pSS. TIGIT negatively regulates the function of NK cells, and reduced TIGITCD56NK cells contribute to the development of pSS disease. In brief, TIGITCD56NK cells might function as a prospective indicator for the assessment of disease progression and outcome prediction in pSS, and may even be regarded as a potential candidate target for immunotherapy in pSS. Key Points • In patients with pSS, there was a reduction in the percentage of TIGIT+CD56+NK cells, particularly among those with active disease. • Our research indicated that a reduction in TIGIT+CD56+NK cell percentage was related with clinical characteristics, laboratory indicators, disease progression, and outcome prediction in patients with pSS. • TIGIT negatively regulates the function of NK cells, and reduced TIGIT+CD56+NK cells contribute to the development of pSS disease.
本研究旨在探讨原发性干燥综合征（pSS）患者外周血中TIGIT⁺CD56⁺NK细胞的表达及临床意义，并研究TIGIT在调节pSS患者NK细胞功能中的作用。
采用流式细胞术检测76例pSS患者和63例健康对照（HCs）外周血中TIGIT⁺CD56⁺NK细胞的百分比。分析不同临床特征、实验室参数以及活动期和非活动期患者中TIGIT⁺CD56⁺NK细胞的百分比。随后，分析pSS患者中TIGIT⁺CD56⁺NK细胞百分比与临床参数之间的相关性。观察10例pSS患者治疗前后TIGIT⁺CD56⁺NK细胞的百分比。此外，构建受试者工作特征（ROC）曲线，评估TIGIT⁺CD56⁺NK细胞百分比在pSS诊断中的价值以及预测pSS疾病活动度。进一步检测5例pSS患者中TIGIT⁺和TIGIT⁻NK细胞分泌的细胞因子水平，以评估NK细胞的功能。
pSS患者中，TIGIT⁺CD56⁺NK细胞百分比降低，尤其是活动期患者。与结果为阴性的患者相比，伴有口干、龋齿、腺体肿大、疲劳、关节痛、皮肤表现、肾小管酸中毒（RTA）、间质性肺病（ILD）、白细胞减少、淋巴细胞减少、血清球蛋白升高、血沉升高、IgG升高、IgA升高以及抗Ro52、抗Ro60和类风湿因子（RF）检测阳性的pSS患者中，TIGIT⁺CD56⁺NK细胞百分比显著降低。CD56⁺NK细胞上TIGIT的表达与血沉、血清球蛋白水平、RF、IgG水平、ESSDAI评分和ESSPRI评分呈负相关。治疗后，TIGIT⁺CD56⁺NK细胞百分比显著增加。ROC曲线表明，TIGIT⁺CD56⁺NK细胞百分比水平在区分pSS和预测疾病活动度方面具有良好能力。发现pSS患者中TIGIT⁻CD56⁺NK细胞中CD69、Ki67、穿孔素、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的表达水平低于TIGIT⁺CD56⁺NK细胞。此外，我们发现穿孔素和TNF-α的表达水平与TIGIT⁺CD56⁺NK细胞的表达水平呈负相关。
我们的研究表明，TIGIT⁺CD56⁺NK细胞百分比降低与pSS患者的临床特征、实验室指标、疾病进展和预后预测相关。TIGIT负向调节NK细胞的功能，TIGIT⁺CD56⁺NK细胞减少促进pSS疾病的发展。简而言之，TIGIT⁺CD56⁺NK细胞可能作为评估pSS疾病进展和预后预测的潜在指标，甚至可能被视为pSS免疫治疗的潜在候选靶点。要点：• pSS患者中，TIGIT⁺CD56⁺NK细胞百分比降低，尤其是活动期患者。• 我们的研究表明，TIGIT⁺CD56⁺NK细胞百分比降低与pSS患者的临床特征、实验室指标、疾病进展和预后预测相关。• TIGIT负向调节NK细胞的功能，TIGIT⁺CD56⁺NK细胞减少促进pSS疾病的发展。
