Al-Ghazzawi Karim, Mairinger Fabian D, Pförtner Roman, Horstmann Mareike, Bechrakis Nikolaos, Mohr Christopher, Eckstein Anja, Oeverhaus Michael
Department of Ophthalmology, University Hospital Essen, 45147 Essen, Germany.
Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
Life (Basel). 2022 Oct 20;12(10):1660. doi: 10.3390/life12101660.
Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are currently treated with non-specific immunosuppressive agents based on non-randomized, uncontrolled studies. Therefore, relapses and prolongated courses are common and remain challenging. For a more specific therapy, a better understanding of the underlying pathophysiology is crucial. Therefore, we aimed to analyze signaling pathways to expand the knowledge on the pathophysiology and possibly identify specific targets in the future, as occurred recently in Graves' orbitopathy with the IGF-1 receptor. Furthermore, we analyzed potential mechanisms for the described potential progression to orbital MALT (mucosa-associated lymphoid tissue) lymphoma. The investigation cohort for this screening study comprised of 12 patients with either typical NSOI (n = 6), IgG4-ROD or MALT lymphoma (n = 3 each). Mean age was 56.4 ± 17 years. MALT samples, in contrast with IgG4-ROD and NSOI, showed overall upregulation for extracellular matrix receptor interaction (ECM) and adipocytokine signaling. Investigating signaling compounds for MALT samples, differentially expressed genes were re-identified as targets with relevant expression. Even though pathway analysis showed differentially altered products when comparing IgG4-ROD with MALT, main conductors of differentiation in B- and T-cell signaling were commonly altered when observing the microenvironment of examined tissues. Our data reveal the characteristic differences and similarities in genetic-expression-based pathway profiles between MALT lymphoma, IgG4-ROD and NSOI, which may be useful for elucidating the associated pathogenic mechanisms and developing specific treatments for these orbital diseases.
基于非随机、非对照研究，目前非特异性眼眶炎症（NSOI）和IgG4相关性眼眶疾病（IgG4-ROD）采用非特异性免疫抑制剂治疗。因此，复发和病程延长很常见，且仍然具有挑战性。对于更具特异性的治疗，深入了解潜在的病理生理学至关重要。因此，我们旨在分析信号通路，以扩展对病理生理学的认识，并可能在未来确定特定靶点，就像最近在格雷夫斯眼病中针对胰岛素样生长因子-1受体所做的那样。此外，我们分析了所描述的向眼眶黏膜相关淋巴组织（MALT）淋巴瘤潜在进展的潜在机制。这项筛查研究的调查队列包括12例患者，其中典型NSOI患者6例，IgG4-ROD或MALT淋巴瘤患者各3例。平均年龄为56.4±17岁。与IgG4-ROD和NSOI相比，MALT样本显示细胞外基质受体相互作用（ECM）和脂肪细胞因子信号总体上调。在研究MALT样本的信号化合物时，差异表达基因被重新确定为具有相关表达的靶点。尽管通路分析显示，将IgG4-ROD与MALT进行比较时产物有差异改变，但在观察所检查组织的微环境时，B细胞和T细胞信号转导的主要调节因子通常会发生改变。我们的数据揭示了MALT淋巴瘤、IgG4-ROD和NSOI之间基于基因表达的通路谱的特征性差异和相似性，这可能有助于阐明相关的致病机制，并为这些眼眶疾病开发特异性治疗方法。
