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Unique cytokine signature in ocular Stevens-Johnson syndrome non-responders
The Ocular Surface ( IF 6.4 ) Pub Date : 2024-03-13 , DOI: 10.1016/j.jtos.2024.03.007
Srividya Gurumurthy , Bhaskar Srinivasan , Shweta Agarwal , Hiren Matai , Narayanasamy Angayarkanni , Geetha Iyer

To clinically define a subset of patients with chronic ocular Stevens-Johnson syndrome non-responders (SJS-NR) and analyze their cytokine profile compared to clinical responders (SJS-CR) A total of 32 SJS cases (n = 32, 64 eyes) managed over a period of three years were segregated into clinical responders (n = 24, 48 eyes) and non-responders (n = 8, 16 eyes). Cases were determined as non-responders based on persistent, refractory, and non-mechanical inflammation of the conjunctiva. Age- and sex-matched healthy controls (n = 25, 50 eyes) were recruited. Tear specimens collected using Schirmer's strip were profiled for 27 cytokines using an immunoassay-based 27-bioplex array. Tear cytokine profiling revealed 18 cytokines to be differentially expressed in SJS-NR compared to SJS-CR. While PDGF-BB, IL-4, IL-1β, VEGF, IL-12p70, IFN-γ, IL-9, and IL-1RA were upregulated, GM-CSF, eotaxin, IP-10, IL-10, MCP-1, G-CSF, IL-6, IL-13, and bFGF were downregulated in SJS-NR compared to SJS-CR. The cytokines IL-13, IL-10, and IP-10 were decreased in both SJS-NR and SJS-CR compared to controls. The inflammation in SJS-NR continues to worsen despite the correction of mechanical causes, resulting in progressive deterioration of the cornea. The cytokine profile of SJS-NR was remarkably different from that of SJS-CR, indicating a T helper 2-type protective proliferative response and an impaired migratory potential of the conjunctival epithelium. These factors could possibly lead to poor healing of the corneal epithelium in a markedly pro-inflammatory and pro-angiogenic milieu. The top four differentially expressed cytokines, PDGF-BB, IL-4, IL-10, and IL-6, are proposed as potential biomarkers of SJS-NR.

中文翻译:

史蒂文斯-约翰逊综合征眼部无反应者的独特细胞因子特征

临床定义慢性眼史蒂文斯​​-约翰逊综合征无反应者 (SJS-NR) 患者的子集,并与临床反应者 (SJS-CR) 相比分析他们的细胞因子谱。 总共 32 例 SJS 病例(n = 32,64 只眼睛)为期三年的管理被分为临床反应者(n = 24,48只眼睛)和无反应者(n = 8,16只眼睛)。根据结膜持续性、难治性和非机械性炎症,将病例确定为无反应者。招募了年龄和性别匹配的健康对照(n = 25,50 只眼睛)。使用基于免疫测定的 27-bioplex 阵列对使用 Schirmer 试纸条收集的泪液样本的 27 种细胞因子进行分析。泪液细胞因子分析显示,与 SJS-CR 相比,SJS-NR 中有 18 种细胞因子的表达存在差异。虽然 PDGF-BB、IL-4、IL-1β、VEGF、IL-12p70、IFN-γ、IL-9 和 IL-1RA 上调,但 GM-CSF、eotaxin、IP-10、IL-10、MCP-如图 1 所示,与 SJS-CR 相比,SJS-NR 中的 G-CSF、IL-6、IL-13 和 bFGF 下调。与对照组相比,SJS-NR 和 SJS-CR 中的细胞因子 IL-13、IL-10 和 IP-10 均减少。尽管机械原因已得到纠正,SJS-NR 的炎症仍在继续恶化,导致角膜进行性恶化。 SJS-NR 的细胞因子谱与 SJS-CR 显着不同,表明 T 辅助细胞 2 型保护性增殖反应和结膜上皮迁移潜力受损。这些因素可能会导致在明显促炎和促血管生成的环境中角膜上皮愈合不良。前四种差异表达的细胞因子:PDGF-BB、IL-4、IL-10 和 IL-6,被提议作为 SJS-NR 的潜在生物标志物。
更新日期:2024-03-13
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