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Abstract：
Immunoglobulin A (IgA) vasculitis (IgAV, also known as Henoch-Schoenlein purpura, HSP) is the most common vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4-12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of inflammation during the window of opportunity between disease presentation and onset of significant nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of nephritis in children with IgAV apart from the early use of corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of complement pathways, amongst others. Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent nephritis in this condition. Key Points • Kidney involvement is the main cause of long-term morbidity and mortality in IgA vasculitis despite the current treatment recommendations. • The evolving understanding of the pathophysiology of IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways. • Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors. • Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis.
摘要：
免疫球蛋白A（IgA）血管炎（IgAV，也被称为过敏性紫癜，HSP）是儿童最常见的血管炎。它通常呈现一个简单的，自我限制的疾病过程;然而,一小部分患者可能发生肾脏受累(IgAV-N),发生在疾病发病后4~12周,是长期发病的最大因素.目前治疗的目标是已确定肾脏受累的患者；然而，人们希望在疾病出现和严重肾炎发作之间的机会窗口中早期预防炎症。除了早期使用无益处的皮质类固醇外，没有临床试验评估可以预防或阻止IgAV儿童肾炎进展的药物。本文总结了最新的科学证据和临床试验，这些证据和临床试验支持目前正在基于对IgAV-N病理生理学的不断发展的理解而开发的IgAV-N的潜在治疗靶标。这些跨越粘膜免疫，B细胞和T细胞调制，RAAS抑制,和调节补体途径，在其他人中。可考虑用于早期肾炎的新药包括TRF-布地奈德;B细胞抑制剂，包括贝利木单抗，telitacicept,blisibimod,VIS649和BION-1301;B细胞消耗剂，如利妥昔单抗，Ofatumumab,和硼替佐米;斯帕生坦;血管紧张素转换酶抑制剂（ACE-Is）;和补体途径抑制剂，包括阿瓦科潘，iptacopan,还有Narsoplimab.进一步的临床试验，以及临床前科学研究，需要确定机制途径，因为在这种情况下可能有机会预防肾炎。要点•肾脏受累是IgA血管炎长期发病和死亡的主要原因，尽管目前的治疗建议。•对IgA血管炎病理生理学的不断发展的理解允许探索靶向潜在免疫途径的新治疗选择。•由于潜在病理生理学的相似性，目前正在IgA肾病中试验的新疗法可能对IgA血管炎有益。如TRF-布地奈德，B细胞调节剂，和补体抑制剂。•进一步研究，包括新药的临床试验，迫切需要改善IgA血管炎肾炎患儿的长期结局。
