Peng Xiang, Lu Yamei, Wei Jianbo, Lin Tianhui, Lu Qinyan, Liu Qiaonan, Ting Wei-Jen
Nephrology Centre, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangdong, China.
Department of Ophthalmology, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangdong, China.
Clin Exp Rheumatol. 2021 Nov-Dec;39 Suppl 133(6):159-165. doi: 10.55563/clinexprheumatol/tlnr4z. Epub 2021 Sep 27.
Sjögren's syndrome (SS) is the most common autoimmune disease with dry eye (DE) syndrome and some systemic lupus erythematosus (SLE) patients are also with DE syndrome. The occurrence of immune-related DE disease is closely related to T helper (Th) 17 cells in SS patients, and SLE patients have abnormal levels of multiple Th17 cell-related cytokines in their blood. However, the degree of expression of these cytokines in blood differs from that in tears. We hypothesised that the occurrence of DE symptoms in SLE and SS patients may be related to Th17 cells.
In this study, Th17 cell-related cytokines, including interleukin (IL)-1β, IL-2, IL-4, interferon-γ, IL 6, IL-8, IL-17F, tumour necrosis factor (TNF)-α, IL-21, IL-22, and IL-23 were analysed in tear samples of DE, SLE, and SS patients. Ocular surface examinations for patients with DE symptoms, including tear secretion test (Schirmer I Test, SIT) and tests for ocular surface disease index (OSDI), tear break-up time (BUT), and corneal fluorescein stain (CFS), were performed and compared between the following patient groups: normal healthy people (control group, n=30), patients with simple DE disease (DE group, n=13), SLE patients with DE disease (SLE group, n=17), and SS patients with DE disease (SS group, n=18).
The expression of Th17 cell-related cytokines in each tear sample was analysed using Luminex assay. The SIT and BUT scores of the SLE group were lower than those of the control (p<0.001) and DE (p<0.05) groups. However, SIT, BUT, CFS, and OSDI scores were not significantly different between SLE and SS patients. TNF-α, IL-6, IL-8, and IL-21 levels in tear samples were higher in DE, SLE, and SS patients (p<0.05) than in control individuals. IL-2 and IL-4 levels in tear samples of SLE patients were higher than DE (p<0.001) but lower than the control (p<0.001) group patients. IL-23 levels in tear samples of DE, SLE, and SS patients were all lower than those in the control group (p<0.001). SIT, BUT, CFS, and OSDI results showed that the DE symptoms of SLE and SS patients were more severe than those of the DE group.
It is known that cytokine expression levels in tears are different from those in blood. Abnormal regulation of the Th17 cell pathway may be related to the occurrence of DE disease in SLE and SS patients, and Th17 cell-related cytokines, such as IL-8 and IL-21, may be potential therapeutic targets for treating SLE or SS DE disease.
干燥综合征(SS)是最常见的伴有干眼(DE)综合征的自身免疫性疾病,一些系统性红斑狼疮(SLE)患者也伴有DE综合征。免疫相关性DE疾病的发生与SS患者的辅助性T(Th)17细胞密切相关,SLE患者血液中多种Th17细胞相关细胞因子水平异常。然而,这些细胞因子在血液中的表达程度与泪液中的不同。我们推测SLE和SS患者DE症状的发生可能与Th17细胞有关。
在本研究中,分析了DE、SLE和SS患者泪液样本中Th17细胞相关细胞因子,包括白细胞介素(IL)-1β、IL-2、IL-4、干扰素-γ、IL-6、IL-8、IL-17F、肿瘤坏死因子(TNF)-α、IL-21、IL-22和IL-23。对有DE症状的患者进行眼表检查,包括泪液分泌试验(Schirmer I试验,SIT)和眼表疾病指数(OSDI)、泪膜破裂时间(BUT)及角膜荧光素染色(CFS)检测,并在以下患者组之间进行比较:正常健康人(对照组,n = 30)、单纯DE疾病患者(DE组,n = 13)、伴有DE疾病的SLE患者(SLE组,n = 17)和伴有DE疾病的SS患者(SS组,n = 18)。
使用Luminex检测法分析各泪液样本中Th17细胞相关细胞因子的表达。SLE组的SIT和BUT评分低于对照组(p < 0.001)和DE组(p < 0.05)。然而,SLE和SS患者之间的SIT、BUT、CFS和OSDI评分无显著差异。DE、SLE和SS患者泪液样本中的TNF-α、IL-6、IL-8和IL-21水平高于对照组个体(p < 0.05)。SLE患者泪液样本中的IL-2和IL-4水平高于DE组(p < 0.001)但低于对照组(p < 0.001)患者。DE、SLE和SS患者泪液样本中的IL-23水平均低于对照组(p < 0.001)。SIT、BUT、CFS和OSDI结果显示,SLE和SS患者的DE症状比DE组更严重。
已知泪液中的细胞因子表达水平与血液中的不同。Th17细胞途径的异常调节可能与SLE和SS患者DE疾病的发生有关,Th17细胞相关细胞因子,如IL-8和IL-21,可能是治疗SLE或SS DE疾病的潜在治疗靶点。