IgA肾病靶向治疗新策略：黏膜免疫、补体途径与肠道微生态的综合视角

A New Strategy of Targeted Therapy for IgA Nephropathy: A Comprehensive Perspective of Mucosal Immunity, Complement Pathway and Intestinal Microecology

摘要: IgA肾病(IgA nephropathy, IgAN)是我国终末期肾病的首要原发因素，传统激素联合免疫抑制剂疗效已达平台且副作用突出。近年来，随着“多重打击”发病模型和肠–肾轴等概念的提出，针对黏膜免疫、补体途径及肠道微生态的靶向干预迅速成为研究热点：布地奈德靶向释放胶囊通过肠道–骨髓回路降低异常IgA1已获III期阳性结果，抗CD20、抗B细胞活化因子(B-cell activating factor, BAFF)等生物制剂正在早期试验中验证安全性；抗C5、抗C5aR1和抗Factor B药物可快速抑制补体激活，显著减少蛋白尿并稳定肾功能；抗生素、益生菌甚至粪菌移植则通过重塑肠道菌群和短链脂肪酸代谢，间接降低半乳糖缺陷型IgA1 (galactose-deficient IgA1, Gd-IgA1)生成和全身炎症。本文回顾上述三方面的最新机制与临床证据，探讨多靶点联合策略的前景与挑战，以期为IgAN的精准治疗提供理论依据与临床实践新策略。

Abstract: IgA nephropathy (IgAN) is the primary factor of end-stage renal disease in China. The efficacy of traditional hormone combined with immunosuppressive agents has reached a plateau and the side effects are prominent. In recent years, with the proposal of the “multiple hit” pathogenesis model and the concept of gut kidney axis, targeted intervention for mucosal immunity, complement pathway and intestinal microecology has rapidly become a research hotspot: Budesonide targeted release capsules have achieved phase III positive results in reducing abnormal IgA1 through the gut bone marrow circuit, and biological agents such as anti-CD20 and anti-B-cell activating factor (BAFF) are being tested in early trials to verify their safety; Anti-C5, anti-c5ar1 and anti factor B drugs can rapidly inhibit complement activation, significantly reduce proteinuria and stabilize renal function; Antibiotics, probiotics and even fecal bacteria transplantation indirectly reduce the production of galactose deficient IgA1 (gd-iga1) and systemic inflammation by remodeling the intestinal flora and short chain fatty acid metabolism. This article reviews the latest mechanism and clinical evidence of the above three aspects, and discusses the prospects and challenges of multi-target combination strategy, in order to provide theoretical basis and new strategies for clinical practice of precision treatment of IgAN.