Bristol Myers Squibb, Princeton, NJ, 08540, USA.
DxTerity®, Rancho Dominguez, CA, USA.
J Transl Med. 2022 Oct 25;20(1):486. doi: 10.1186/s12967-022-03682-3.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition that can lead to severe impairment of physical, psychological, cognitive, social, and occupational functions. The cause of ME/CFS remains incompletely understood. There is no clinical diagnostic test for ME/CFS. Although many therapies have been used off-label to manage symptoms of ME/CFS, there are limited, if any, specific therapies or cure for ME/CFS. In this study, we investigated the expression of genes specific to key immune functions, and viral infection status in ME/CFS patients with an aim of identifying biomarkers for characterization and/or treatment of the disease.
In 2021, one-hundred and sixty-six (166) patients diagnosed with ME/CFS and 83 healthy controls in the US participated in this study via a social media-based application (app). The patients and heathy volunteers consented to the study and provided self-collected finger-stick blood and first morning void urine samples from home. RNA from the fingerstick blood was tested using DxTerity's 51-gene autoimmune RNA expression panel (AIP). In addition, DNA from the same fingerstick blood sample was extracted to detect viral load of 4 known ME/CFS associated viruses (HHV6, HHV7, CMV and EBV) using a real-time PCR method.
Among the 166 ME/CFS participants in the study, approximately half (49%) of the ME/CFS patients reported being house-bound or bedridden due to severe symptoms of the disease. From the AIP testing, ME/CFS patients with severe, bedridden conditions displayed significant increases in gene expression of IKZF2, IKZF3, HSPA8, BACH2, ABCE1 and CD3D, as compared to patients with mild to moderate disease conditions. These six aforementioned genes were further upregulated in the 22 bedridden participants who suffer not only from ME/CFS but also from other autoimmune diseases. These genes are involved in T cell, B cell and autoimmunity functions. Furthermore, IKZF3 (Aiolos) and IKZF2 (Helios), and BACH2 have been implicated in other autoimmune diseases such as systemic lupus erythematosus (SLE) and Rheumatoid Arthritis (RA). Among the 240 participants tested with the viral assays, 9 samples showed positive results (including 1 EBV positive and 8 HHV6 positives).
Our study indicates that gene expression biomarkers may be used in identifying or differentiating subsets of ME/CFS patients having different levels of disease severity. These gene targets may also represent opportunities for new therapeutic modalities for the treatment of ME/CFS. The use of social media engaged patient recruitment and at-home sample collection represents a novel approach for conducting clinical research which saves cost, time and eliminates travel for office visits.
肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）是一种使人衰弱的疾病，可导致身体、心理、认知、社会和职业功能严重受损。ME/CFS 的病因仍不完全清楚。目前没有针对 ME/CFS 的临床诊断测试。尽管有许多治疗方法已被用于治疗 ME/CFS 的症状，但针对 ME/CFS 并没有特定的治疗方法或治愈方法。在这项研究中，我们研究了特定于关键免疫功能的基因的表达和病毒感染状态，旨在确定用于表征和/或治疗该疾病的生物标志物。
2021 年，美国有 166 名被诊断患有 ME/CFS 的患者和 83 名健康对照者通过基于社交媒体的应用程序（app）参与了这项研究。患者和健康志愿者同意参与这项研究，并在家中自行采集指尖血和晨尿样本。使用 DxTerity 的 51 个基因自身免疫 RNA 表达谱（AIP）测试指尖血中的 RNA。此外，从同一指尖血样中提取 DNA，使用实时 PCR 方法检测 4 种已知与 ME/CFS 相关的病毒（HHV6、HHV7、CMV 和 EBV）的病毒载量。
在研究中的 166 名 ME/CFS 参与者中，约一半（49%）的 ME/CFS 患者因疾病的严重症状而处于足不出户或卧床不起的状态。通过 AIP 测试，与病情较轻至中度的患者相比，病情严重、卧床不起的 ME/CFS 患者的 IKZF2、IKZF3、HSPA8、BACH2、ABCE1 和 CD3D 基因表达显著增加。在 22 名不仅患有 ME/CFS 而且患有其他自身免疫性疾病的卧床不起参与者中，上述六个基因进一步上调。这些基因参与 T 细胞、B 细胞和自身免疫功能。此外，IKZF3（Aiolos）和 IKZF2（Helios）以及 BACH2 已被牵连到其他自身免疫性疾病，如系统性红斑狼疮（SLE）和类风湿关节炎（RA）。在接受病毒检测的 240 名参与者中，有 9 份样本呈阳性（包括 1 份 EBV 阳性和 8 份 HHV6 阳性）。
我们的研究表明，基因表达生物标志物可用于识别或区分具有不同疾病严重程度的 ME/CFS 患者亚组。这些基因靶点也可能为治疗 ME/CFS 的新治疗方法提供机会。使用社交媒体招募患者并在家中采集样本代表了一种进行临床研究的新方法，可节省成本、时间并避免因就诊而出行。
