Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Nephrology, Dialysis and Transplantation Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Int J Mol Sci. 2024 Oct 16;25(20):11096. doi: 10.3390/ijms252011096.
Epitope spreading is a critical mechanism driving the progression of autoimmune glomerulonephritis. This phenomenon, where immune responses broaden from a single epitope to encompass additional targets, contributes to the complexity and severity of diseases such as membranous nephropathy (MN), lupus nephritis (LN), and ANCA-associated vasculitis (AAV). In MN, intramolecular spreading within the phospholipase A2 receptor correlates with a worse prognosis, while LN exemplifies both intra- and intermolecular spreading, exacerbating renal involvement. Similarly, ANCA reactivity in AAV highlights the destructive potential of epitope diversification. Understanding these immunological cascades reveals therapeutic opportunities-targeting early epitope spreading could curb disease progression. Despite promising insights, the clinical utility of epitope spreading as a prognostic tool remains debated. This review provides a complete overview of the current evidence, exploring the dual-edged nature of epitope spreading, the intricate immune mechanisms behind it, and its therapeutic implications. By elucidating these dynamics, we aim to pave the way for more precise, targeted interventions in autoimmune glomerular diseases.
表位扩展是驱动自身免疫性肾小球肾炎进展的关键机制。这种免疫反应从单一表位扩展到包含更多靶标的现象，导致了膜性肾病（MN）、狼疮性肾炎（LN）和抗中性粒细胞胞质抗体相关性血管炎（AAV）等疾病的复杂性和严重性。在 MN 中，磷脂酶 A2 受体内部的分子内扩展与预后不良相关，而 LN 则同时体现了分子内和分子间的扩展，加重了肾脏受累。同样，AAV 中的 ANC 反应突出了表位多样化的破坏性潜力。了解这些免疫级联反应揭示了治疗机会——靶向早期表位扩展可能会抑制疾病进展。尽管有很有前景的见解，但表位扩展作为一种预后工具的临床实用性仍存在争议。本综述提供了当前证据的全面概述，探讨了表位扩展的双重性质、其背后复杂的免疫机制及其治疗意义。通过阐明这些动态，我们旨在为自身免疫性肾小球疾病的更精确、靶向干预铺平道路。
