Department of Immunopathology, Post Graduate Institute of Medical Education and Research, India.
Lupus. 2012 Sep;21(10):1105-12. doi: 10.1177/0961203312451200. Epub 2012 Jun 29.
Paediatric systemic lupus erythematosus (pSLE) exhibits an aggressive clinical phenotype and severe complications commonly renal involvement. This could be reflective of the ongoing chronic pro-inflammatory cytokine milieu. We examined relative gene expression of tumour necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and serum levels of interleukin-17 (IL-17) and IL-23 and their association with SLEDAI (SLE disease activity index) score and organ manifestations in pSLE.
We enrolled 40 pSLE patients (age 5-16 years, on treatment) and 20 age-matched healthy controls. Relative gene expression levels of IFN-γ and TNF-α in the peripheral blood were determined by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). β actin gene was used for normalization of gene expression. Serum levels of IL-17 and IL-23 were determined by solid phase sandwich ELISA. Statistical analysis were carried out for comparing (Mann-Whitney U test) and correlating data (Univariate, multivariate analysis and Pearson correlation test) with SLEDAI scores and clinical manifestations.
Over-expression of TNF-α and IFN-γ was found in 90% (36/40) and 80% (32/40) of pSLE patients, respectively. The relative gene expression of TNF-α and IFN-γ were significantly correlated with renal manifestations (p < 0.05). Further, relative expression of IFN-γ gene correlated significantly with skin manifestations and SLEDAI (p < 0.05). Serum levels of IL-17 (766.95 ± 357.83 pg/ml) and IL-23 (135.4 ± 54.23 pg/ml) in pSLE were significantly higher than in controls (IL-17, 172.7 ± 39.19 pg/ml and IL-23, 21.15 ± 10.99 pg/ml) (p < 0.05). Patients with cutaneous (p = 0.002) and haematological involvement (p = 0.003) had high serum IL-17 levels. Serum IL-17 levels correlated with SLEDAI (r = 0.447; p < 0.05).
In this preliminary study, we observed a persistent, strong pro-inflammatory cytokine milieu in pSLE patients which reflects ongoing inflammatory damage in different organs. The gene expression profile of these cytokines may be used for assessing organ involvement in pSLE. IL-17 may also serve as a prognostic marker in pSLE. However, longitudinal studies on treatment of naïve patients are required to corroborate these findings.
儿科系统性红斑狼疮（pSLE）表现出侵袭性临床表型和严重并发症，常见肾脏受累。这可能反映了持续存在的慢性促炎细胞因子环境。我们研究了肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）的相对基因表达以及白细胞介素-17（IL-17）和白细胞介素-23（IL-23）的血清水平及其与 pSLE 的SLE 疾病活动指数（SLEDAI）评分和器官表现的关系。
我们纳入了 40 例 pSLE 患者（年龄 5-16 岁，正在接受治疗）和 20 名年龄匹配的健康对照者。通过实时定量逆转录聚合酶链反应（RT-PCR）测定外周血中 IFN-γ和 TNF-α的相对基因表达。β肌动蛋白基因用于基因表达的归一化。通过固相夹心 ELISA 测定血清中 IL-17 和 IL-23 的水平。采用 Mann-Whitney U 检验比较（Mann-Whitney U 检验）和相关数据（单变量、多变量分析和 Pearson 相关检验）与 SLEDAI 评分和临床表现。
90%（36/40）和 80%（32/40）的 pSLE 患者分别发现 TNF-α和 IFN-γ过度表达。TNF-α和 IFN-γ的相对基因表达与肾脏表现显著相关（p<0.05）。此外，IFN-γ基因的相对表达与皮肤表现和 SLEDAI 显著相关（p<0.05）。pSLE 患者的血清 IL-17（766.95±357.83pg/ml）和 IL-23（135.4±54.23pg/ml）水平明显高于对照组（IL-17，172.7±39.19pg/ml 和 IL-23，21.15±10.99pg/ml）（p<0.05）。有皮肤（p=0.002）和血液学受累（p=0.003）的患者血清 IL-17 水平较高。血清 IL-17 水平与 SLEDAI 相关（r=0.447；p<0.05）。
在这项初步研究中，我们观察到 pSLE 患者持续存在强烈的促炎细胞因子环境，反映了不同器官的持续炎症损伤。这些细胞因子的基因表达谱可用于评估 pSLE 的器官受累情况。IL-17 也可作为 pSLE 的预后标志物。然而，需要对初治患者进行纵向研究来证实这些发现。
