Department of Health Sciences, University of Firenze, Firenze, Italy; Immunology Unit, Department of Pediatrics, Meyer Children's Hospital, Firenze, Italy.
Rheumatology Unit, Department of Pediatrics, Meyer Children's Hospital, Firenze, Italy.
Kidney Int. 2022 Jun;101(6):1142-1159. doi: 10.1016/j.kint.2022.02.031. Epub 2022 Mar 24.
Type I interferon (IFN-I) mediates tissue damage in a wide range of kidney disorders, directly affecting the biology and function of several renal cell types including podocytes, mesangial, endothelial, and parietal epithelial cells. Enhanced IFN-I signaling is observed in the context of viral infections, autoimmunity (e.g., systemic lupus erythematosus), and type 1 interferonopathies, rare monogenic disorders characterized by constitutive activation of the IFN-I pathway. All these IFN-I-related disorders can cause renal dysfunction and share pathogenic and histopathological features. Collapsing glomerulopathy, a histopathological lesion characterized by podocyte loss, collapse of the vascular tuft, and parietal epithelial cell proliferation, is commonly associated with viral infections, has been described in type 1 interferonopathies such as Aicardi-Goutières syndrome and stimulator of IFN genes-associated vasculopathy with onset in infancy, and can also be induced by recombinant IFN therapy. In all these conditions, podocytes and parietal epithelial cells seem to be the primary target of IFN-I-mediated damage. Additionally, immune-mediated glomerular injury is common to viral infections, systemic lupus erythematosus, and type 1 interferonopathies such as coatomer subunit-α syndrome (COPA) and DNASE1L3 deficiency, diseases in which IFN-I apparently promotes immune-mediated kidney injury. Finally, kidney pathology primarily characterized by vascular lesions (e.g., thrombotic microangiopathy and vasculitis) is a hallmark of type 1 interferonopathy adenosine deaminase 2 deficiency as well as of systemic lupus erythematosus, viral infections, and IFN therapy. Defining the nosology, pathogenic mechanisms, and histopathological patterns of IFN-I-related kidney disorders has diagnostic and therapeutic implications, especially considering the likely near-term availability of novel drugs targeting the IFN-I pathway.
I 型干扰素 (IFN-I) 在广泛的肾脏疾病中介导组织损伤，直接影响包括足细胞、系膜、内皮和壁层上皮细胞在内的几种肾细胞类型的生物学和功能。在病毒感染、自身免疫（例如系统性红斑狼疮）和 I 型干扰素病的情况下观察到增强的 IFN-I 信号，这些罕见的单基因疾病的特征是 IFN-I 途径的组成性激活。所有这些与 IFN-I 相关的疾病都可导致肾功能障碍，并具有共同的发病和组织病理学特征。塌陷性肾小球病是一种组织病理学病变，其特征是足细胞丧失、血管丛塌陷和壁层上皮细胞增殖，通常与病毒感染有关，已在 I 型干扰素病如 Aicardi-Goutières 综合征和刺激 IFN 基因相关血管病中描述，这些疾病在婴儿期发病，也可由重组 IFN 治疗诱导。在所有这些情况下，足细胞和壁层上皮细胞似乎是 IFN-I 介导损伤的主要靶标。此外，免疫介导的肾小球损伤在病毒感染、系统性红斑狼疮和 I 型干扰素病（如衣壳蛋白亚单位-α 综合征 (COPA) 和 DNASE1L3 缺乏症）中很常见，在这些疾病中 IFN-I 显然促进了免疫介导的肾脏损伤。最后，主要以血管病变为特征的肾脏病理学（例如血栓性微血管病和血管炎）是 I 型干扰素病腺苷脱氨酶 2 缺乏症以及系统性红斑狼疮、病毒感染和 IFN 治疗的特征。定义 IFN-I 相关肾脏疾病的分类学、发病机制和组织病理学模式具有诊断和治疗意义，尤其是考虑到新型靶向 IFN-I 途径的药物可能很快就会问世。
