R. S. Mehta Jain Dept. of Biochemistry and Cell Biology, KBIRVO, Vision Research Foundation, Chennai, 600 006, India.
C. J. Shah Cornea Services, Dr. G Sitalakshmi Memorial Clinic for Ocular Disorders, SN-Sanmar Center of Excellence for SJS, Medical Research Foundation, Sankara Nethralaya, Chennai, 600 006, India.
Ocul Surf. 2024 Apr;32:173-181. doi: 10.1016/j.jtos.2024.03.007. Epub 2024 Mar 13.
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.
从临床上定义慢性眼部史蒂文斯-约翰逊综合征无反应者（SJS-NR）亚组患者，并分析其细胞因子谱与临床反应者（SJS-CR）相比的差异。
将三年内收治的 32 例 SJS 患者（n=32，64 只眼）分为临床反应者（n=24，48 只眼）和无反应者（n=8，16 只眼）。无反应者的确定基于持续性、难治性和非机械性结膜炎炎症。招募年龄和性别匹配的健康对照者（n=25，50 只眼）。使用 Schirmer 条收集的泪液标本使用基于免疫测定的 27 生物素芯片阵列对 27 种细胞因子进行分析。
泪液细胞因子谱分析显示，与 SJS-CR 相比，SJS-NR 中有 18 种细胞因子表达差异。SJS-NR 中 PDGF-BB、IL-4、IL-1β、VEGF、IL-12p70、IFN-γ、IL-9 和 IL-1RA 上调，而 GM-CSF、eotaxin、IP-10、IL-10、MCP-1、G-CSF、IL-6、IL-13 和 bFGF 下调。与 SJS-CR 相比，SJS-NR 和 SJS-CR 中细胞因子 IL-13、IL-10 和 IP-10 均降低。
尽管纠正了机械原因，但 SJS-NR 的炎症仍继续恶化，导致角膜进行性恶化。SJS-NR 的细胞因子谱与 SJS-CR 明显不同，表明辅助性 T 细胞 2 型保护性增殖反应和结膜上皮迁移潜能受损。这些因素可能导致角膜上皮在明显的促炎和促血管生成环境中愈合不良。提出 PDGF-BB、IL-4、IL-10 和 IL-6 这四种差异表达的细胞因子作为 SJS-NR 的潜在生物标志物。
