Laboratory for Cell Genetics, Department Biology, Faculty of Sciences and Bio-engineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.
Environmental Carcinogenesis Unit, Ospedale Policlinico San Martino, 16132 Genoa, Italy.
Mutat Res Rev Mutat Res. 2020 Oct-Dec;786:108335. doi: 10.1016/j.mrrev.2020.108335. Epub 2020 Sep 15.
Auto-immune diseases (AUD) are characterized by an immune response to antigenic components of the host itself. The etiology of AUD is not well understood. The available evidence points to an interaction between genetic, epigenetic, environmental, infectious and life-style factors. AUD are more prevalent in women than in men; sex hormones play a crucial role in this sex bias. Micronuclei (MN) emerged as a new player in the induction of AUD, based on the capacity of DNA-sensors to detect self-DNA that leaks into the cytoplasm from disrupted MN and induce the cGAS-STING pathway triggering an innate auto-immune response and chronic inflammation. It was found that inflammation can induce MN and MN can induce inflammation, leading to a vicious inflammation-oxidative-DNA damage-MN-formation-chromothripsis cycle. MN originating from sex chromosome-loss may induce inflammation and AUD. We performed a systematic review of studies reporting MN in patients with systemic or organ-specific AUD. A meta-analysis was performed on lymphocyte MN in diabetes mellitus (10 studies, 457 patients/290 controls) and Behcet's disease (3 studies, 100 patients/70 controls) and for buccal MN in diabetes mellitus (11 studies, 507 patients/427 controls). A statistically significant increase in patients compared to controls was found in the meta-analyses providing an indication of an association between MN and AUD. A 36%-higher mean-MRi in buccal cells (3.8+/-0.7) was found compared to lymphocytes (2.8+/-0.7)(P = 0.01). The meta-MRi in lymphocytes and buccal cells (1.7 and 3.0 respectively) suggest that buccal cells may be more sensitive. To assess their relative sensitivity, studies with measurements from the same subjects would be desirable. It is important that future studies (i) investigate, in well-designed powered studies, the prospective association of MN-formation with AUD and (ii) explore the molecular mechanisms by which chromosome shattering in MN and the release of chromatin fragments from MN lead to the formation of auto-antibodies.
自身免疫性疾病（AUD）的特征是针对宿主自身抗原的免疫反应。AUD 的病因尚不清楚。现有证据表明，遗传、表观遗传、环境、感染和生活方式等因素相互作用。AUD 在女性中的发病率高于男性；性激素在这种性别偏差中起着至关重要的作用。微核（MN）作为诱导 AUD 的新参与者出现，基于 DNA 传感器检测从受损 MN 漏入细胞质的自身 DNA 的能力，并诱导 cGAS-STING 途径触发先天自身免疫反应和慢性炎症。据发现，炎症可以诱导 MN，MN 可以诱导炎症，导致炎症-氧化-DNA 损伤-MN 形成-染色体重排的恶性循环。源自性染色体缺失的 MN 可能会引发炎症和 AUD。我们对报告系统性或器官特异性 AUD 患者 MN 的研究进行了系统评价。对糖尿病（10 项研究，457 例患者/290 例对照）和贝切特病（3 项研究，100 例患者/70 例对照）的淋巴细胞 MN 以及糖尿病的口腔 MN（11 项研究，507 例患者/427 例对照）进行了荟萃分析。荟萃分析显示，与对照组相比，患者的 MN 明显增加，表明 MN 与 AUD 之间存在关联。与淋巴细胞（2.8+/-0.7）相比，口腔细胞的平均-MRi 高 36%（3.8+/-0.7）（P = 0.01）。淋巴细胞和口腔细胞的荟萃-MRi（分别为 1.7 和 3.0）表明口腔细胞可能更敏感。为了评估它们的相对敏感性，最好进行来自同一受试者的测量的研究。重要的是，未来的研究（i）在精心设计的、有影响力的研究中，调查 MN 形成与 AUD 的前瞻性关联，（ii）探索 MN 中染色体破碎和 MN 中染色质片段释放导致自身抗体形成的分子机制。
