Department of Emergency and Organ Transplant, University of Bari, Bari, Italy.
Schena Foundation, Policlinic, Bari, Italy.
Semin Immunopathol. 2021 Oct;43(5):691-705. doi: 10.1007/s00281-021-00891-8. Epub 2021 Oct 21.
Kidney biopsy is the cornerstone for the diagnosis of immunoglobulin A nephropathy (IgAN). The immunofluorescence technique evidences the IgA deposits in the glomeruli; the routine histology shows degree of active and chronic renal lesions. The spectrum of renal lesions is highly variable, ranging from minor or no detectable lesions to diffuse proliferative or crescentic lesions. Over the past three decades, renal transcriptomic studies have been performed on fresh or frozen renal tissue, and formalin-fixed paraffin-embedded kidney tissue specimens obtained from archival histological repositories. This paper aims to describe (1) the transcriptomic profiles of the kidney biopsy and (2) the potential urinary biomarkers that can be used to monitor the follow-up of IgAN patients. The use of quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), microarrays and RNA-sequencing (RNA-seq) techniques on renal tissue and separated compartments of the nephron such as glomeruli and tubule-interstitium has clarified many aspects of the renal damage in IgAN. Recently, the introduction of the single-cell RNA-seq techniques has overcome the limitations of the previous methods, making that it is possible to study the whole renal tissue without the dissection of the nephron segments; it also allows better analysis of the cell-specific gene expression involved in cell differentiation. These gene products could represent effective candidates for urinary biomarkers for clinical decision making. Finally, some of these molecules may be the targets of old drugs, such as corticosteroids, renin-angiotensin-aldosterone blockers, and new drugs such as monoclonal antibodies. In the era of personalized medicine and precision therapy, high-throughput technologies may better characterize different renal patterns of IgAN and deliver targeted treatments to individual patients.
肾活检是诊断免疫球蛋白 A 肾病（IgAN）的基石。免疫荧光技术可证实肾小球内 IgA 沉积；常规组织学显示活跃和慢性肾损伤程度。肾损伤谱高度可变，从轻微或无法检测到的病变到弥漫性增生性或新月体性病变不等。在过去的三十年中，对新鲜或冷冻肾组织以及来自存档组织学库的福尔马林固定石蜡包埋肾组织标本进行了肾转录组学研究。本文旨在描述（1）肾活检的转录组谱，（2）可用于监测 IgAN 患者随访的潜在尿生物标志物。定量实时聚合酶链反应（qRT-PCR）、微阵列和 RNA 测序（RNA-seq）技术在肾组织和肾单位的分离区室（如肾小球和小管间质）中的应用，阐明了 IgAN 肾损伤的许多方面。最近，单细胞 RNA-seq 技术的引入克服了以前方法的局限性，使得有可能在不分离肾单位的情况下研究整个肾组织；它还允许更好地分析参与细胞分化的细胞特异性基因表达。这些基因产物可能是用于临床决策的尿生物标志物的有效候选物。最后，其中一些分子可能是旧药物（如皮质类固醇、肾素-血管紧张素-醛固酮阻滞剂）和新药物（如单克隆抗体）的靶点。在个性化医学和精准治疗时代，高通量技术可能更好地描述 IgAN 的不同肾脏模式，并为个体患者提供靶向治疗。
