Non-Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology that can be difficult to diagnose. In this study we aim to identify serum miRNAs associated with NHOL and IOI. We performed OpenArray® miRNA profiling in 33 patients and controls. Differentially expressed miRNAs were technically validated across technology platforms and replicated in an additional cohort of 32 patients and controls. We identified and independently validated a serum miRNA profile of NHOL that was remarkably similar to IOI and characterized by an increased expression of a cluster of eight miRNAs. Pathway enrichment analysis indicated that the miRNA-cluster is associated with immune-mediated pathways, which we supported by demonstrating the elevated expression of this cluster in serum of patients with other inflammatory conditions. The cluster contained miR-148a, a key driver of B-cell tolerance, and miR-365 that correlated with serum IgG and IgM concentrations. In addition, miR-29a and miR-223 were associated with blood lymphocyte and neutrophil populations, respectively. NHOL and IOI are characterized by an abnormal serum miRNA-cluster associated with immune pathway activation and linked to B cell and neutrophil dysfunction.

中文翻译：

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泛炎性 microRNA 簇与眼眶非霍奇金淋巴瘤和特发性眼眶炎症相关。

非霍奇金眼眶淋巴瘤 (NHOL) 和特发性眼眶炎症 (IOI) 是常见的眼眶疾病，其病理生理学很大程度上未知，很难诊断。在本研究中，我们的目的是鉴定与 NHOL 和 IOI 相关的血清 miRNA。我们对 33 名患者和对照进行了 OpenArray® miRNA 分析。差异表达的 miRNA 在各个技术平台上进行了技术验证，并在另外 32 名患者和对照组的队列中进行了复制。我们鉴定并独立验证了 NHOL 的血清 miRNA 谱，该谱与 IOI 非常相似，其特征是八个 miRNA 簇的表达增加。通路富集分析表明 miRNA 簇与免疫介导的通路相关，我们通过证明该簇在其他炎症性疾病患者的血清中表达升高来支持这一点。该簇包含 miR-148a（B 细胞耐受的关键驱动因素）和 miR-365（与血清 IgG 和 IgM 浓度相关）。此外，miR-29a 和 miR-223 分别与血液淋巴细胞和中性粒细胞群相关。NHOL 和 IOI 的特点是异常的血清 miRNA 簇，与免疫通路激活相关，并与 B 细胞和中性粒细胞功能障碍有关。