Department of Ophthalmology, University Hospital Essen, 45147 Essen, Germany.
Department of Oral and Maxillofacial Surgery, University of Duisburg-Essen, Kliniken-Essen-Mitte, 45136 Essen, Germany.
Int J Mol Sci. 2022 Aug 3;23(15):8609. doi: 10.3390/ijms23158609.
Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000−2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.
非特异性眼眶炎症（NSOI）和 IgG4 相关眼眶疾病（IgG4-ROD）常难以鉴别。此外，慢性炎症（如 IgG4-ROD）如何导致黏膜相关淋巴组织（MALT）淋巴瘤仍不确定。因此，我们旨在评估基因表达分析对鉴别眼眶自身免疫性疾病和阐明遗传重叠的诊断价值。首先，我们建立了我们眼眶中心的 NSOI、复发性 NSOI、IgG4-ROD 和 MALT 淋巴瘤患者数据库（2000-2019）。在一个共识过程中，选择了上述三组中三个典型患者（平均年龄 56.4 ± 17 岁），且位于相似部位。随后，使用 RNeasy FFPE 试剂盒（Qiagen）从存档的石蜡包埋组织中分离 RNA。对这 12 名患者的 RNA 进行基因表达分析（NanoString nCounter®），包括总共 1364 个靶基因。使用机器学习算法区分实体的最显著上调和下调基因。这是可能的，概率很高（p < 0.0001）。有趣的是，基因表达模式显示出淋巴瘤与 IgG4-ROD 和 NSOI 的特征重叠。相比之下，IgG4-ROD 与 NSOI 仅共享一个基因的改变表达。为了验证我们的潜在生物标志物基因，我们分离了另外 48 名患者（24 名 NSOI、11 名 IgG4-ROD、13 名淋巴瘤患者）的 RNA。然后，使用定制设计的 CodeSet 对 35 个鉴定的靶基因进行基因表达模式分析，以评估多参数评分算法的预测准确性。它们表现出高准确性和良好的性能（AUC ROC：IgG4-ROD 0.81、MALT 0.82、NSOI 0.67）。总之，基因表达分析有可能更快、更安全地区分 NSOI 和 IgG4-ROD。MALT 淋巴瘤和 IgG4-ROD 显示出更多的遗传相似性，这表明向淋巴瘤进展。
