Peliçari Karina de Oliveira, Postal Mariana, Sinicato Nailú Angelica, Londe Ana Carolina, Fernandes Paula Teixeira, Marini Roberto, Costallat Lilian Tereza Lavras, Appenzeller Simone
Rheumatology Lab, School of Medical Sciences, University of Campinas, Brazil.
Child and Adolescent Health Graduate Program - School of Medical Science - University of Campinas, Brazil.
J Transl Autoimmun. 2022 May 26;5:100158. doi: 10.1016/j.jtauto.2022.100158. eCollection 2022.
To compare the levels of Th1 (IL-12) and Th2 (IL-6 and IL10) cytokines over a two-year period among systemic lupus erythematosus patients with childhood-onset (cSLE), adult-onset (sSLE), and healthy controls, and correlate with their clinical, laboratory, and treatment manifestations.
The study included 63 patients with cSLE [57 (90%) women; mean age 19.7 ± 4.3 years (range = 10-29); mean disease duration 7.3 ± 4.2 years (range 2-15)], 67 patients with aSLE [65 (97%) women; mean age of 39.9 ± 11.8 years (range 21-68); disease duration 7.7 ± 3.1 years (range 4-16)], and 40 healthy controls [36 (90%) women; mean age of 29.6 ± 10 years (range 12-49)]. cSLE and aSLE patients were paired by disease duration. Clinical and laboratory manifestations, disease activity (SLEDAI), cumulative damage (SDI), and current drug exposures were evaluated. Symptoms of anxiety and depression were evaluated by the Beck inventory (BAI and BDI, respectively). Th1 (IL-12) and Th2 (IL-6 and IL-10) cytokines were measured by the ELISA test. Data were collected at four different time points (TI, TII, TIII, and TIV) and compared by non-parametric tests.
IL-6 levels were significantly higher in aSLE patients compared to healthy controls at times I, II, and III (TI p = 0.013, TII p = 0.015, TIII p = 0.004, and TIV p = 0.634). However, no difference was observed between cSLE patients and healthy controls (TI p = 0.223, TII p = 0.613, TIII p = 0.341, and TIV p = 0.977). In addition, no difference was observed between aSLE and cSLE patients (TI p = 0.377, TII p = 0.123, TIII p = 0.105, and TIV p = 0.591). The levels of IL-12 were significantly higher in cSLE patients compared to healthy controls at all time points (TI p = 0.04, TII p < 0.001, TIII p = 0.015, and TIV p = 0.021). aSLE patients showed significantly elevated levels when compared to healthy controls at time III and IV (TI p = 0.752, TII p = 0.827, TIII p = 0.011*, and TIV p < 0.001*). cSLE patients showed significantly higher levels than aSLE patients at times I and II (TI p = 0.07*, TII p < 0.001*, TIII p = 0.998, and TIV p = 0.140). In aSLE patients, IL-6 was associated with headache (p = 0.006), arthritis (p = 0.044), and nephritis (p = 0.012); IL-10 was associated with nephritis (p = 0.043), hypocomplementemia (p = 0.001), and disease activity (p = 0.001); in these patients, IL-12 was associated with alopecia (p = 0.025) and leukopenia (p = 0.044). In cSLE patients, IL-6 was associated with arthritis (p = 0.022) and malar rash (p = 0.012).
aSLE and cSLE patients with long disease duration present similar levels of cytokines, despite differences in clinical activity patterns over time.
比较儿童期起病的系统性红斑狼疮（cSLE）患者、成人期起病的系统性红斑狼疮（aSLE）患者和健康对照者在两年时间内Th1（白细胞介素-12，IL-12）和Th2（白细胞介素-6，IL-6；白细胞介素-10，IL-10）细胞因子的水平，并将其与临床、实验室及治疗表现相关联。
该研究纳入63例cSLE患者[57例（90%）为女性；平均年龄19.7±4.3岁（范围10 - 29岁）；平均病程7.3±4.2年（范围2 - 15年）]、67例aSLE患者[65例（97%）为女性；平均年龄39.9±11.8岁（范围21 - 68岁）；病程7.7±3.1年（范围4 - 16年）]以及40例健康对照者[36例（90%）为女性；平均年龄29.6±10岁（范围12 - 49岁）]。cSLE患者和aSLE患者按病程配对。评估临床和实验室表现、疾病活动度（SLEDAI）、累积损伤（SDI）及当前药物暴露情况。分别通过贝克焦虑量表（BAI）和贝克抑郁量表（BDI）评估焦虑和抑郁症状。采用酶联免疫吸附测定（ELISA）法检测Th1（IL-12）和Th2（IL-6和IL-10）细胞因子。在四个不同时间点（TⅠ、TⅡ、TⅢ和TⅣ）收集数据，并通过非参数检验进行比较。
与健康对照者相比，aSLE患者在时间点Ⅰ、Ⅱ和Ⅲ时IL-6水平显著更高（TⅠ，p = 0.013；TⅡ，p = 0.015；TⅢ，p = 0.004；TⅣ，p = 0.634）。然而，cSLE患者与健康对照者之间未观察到差异（TⅠ，p = 0.223；TⅡ，p = 0.613；TⅢ，p = 0.341；TⅣ，p = 0.977）。此外，aSLE患者与cSLE患者之间也未观察到差异（TⅠ，p = 0.377；TⅡ，p = 0.123；TⅢ，p = 0.105；TⅣ，p = 0.591）。在所有时间点，cSLE患者的IL-12水平均显著高于健康对照者（TⅠ，p = 0.04；TⅡ，p < 0.001；TⅢ，p = 0.015；TⅣ，p = 0.021）。与健康对照者相比，aSLE患者在时间点Ⅲ和Ⅳ时IL-12水平显著升高（TⅠ，p = 0.752；TⅡ，p = 0.827；TⅢ，p = 0.011*；TⅣ，p < 0.001*）。在时间点Ⅰ和Ⅱ时，cSLE患者的IL-12水平显著高于aSLE患者（TⅠ，p = 0.07*；TⅡ，p < 0.001*；TⅢ，p = 0.998；TⅣ，p = 0.140）。在aSLE患者中，IL-6与头痛（p = 0.006）、关节炎（p = 0.044）和肾炎（p = 0.012）相关；IL-10与肾炎（p = 0.043）、低补体血症（p = 0.001）和疾病活动度（p = 0.001）相关；在这些患者中，IL-12与脱发（p = 0.025）和白细胞减少（p = 0.044）相关。在cSLE患者中，IL-6与关节炎（p = 0.022）和蝶形红斑（p = 0.012）相关。
尽管随着时间推移临床活动模式存在差异，但病程较长的aSLE和cSLE患者的细胞因子水平相似。
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