从BAFF-TACI信号通路探讨IgA分泌B淋巴细胞归巢在IgA肾病发病中的作用及益气清解方的干预机制

IgA肾病（IgAN）是最重要的原发肾小球疾病，多方证据表明黏膜免疫异常致血清低半乳糖基化IgA1（GD-IgA1）增多与发病直接关联；分泌型IgA1生成过量及IgA+浆/B细胞错位归巢至骨髓是GD-IgA1来源；BAFF及其受体TACI在上述非T细胞依赖的B细胞成熟和向分泌IgA类别转化起关键作用。我们观察到IgAN患者因“黏膜感染”症状而表现为“风热、湿热”证，并与GD-IgA1水平相关，益气清解方可显著减轻症状并改善预后，据此我们提出“肺脾气虚、卫气不固、风湿热毒伤肾”是IgAN病机，益气清解方作用机制可能与调控BAFF-TACI信号、减少IgA分泌细胞生成过度和错位归巢，进而减少GD-IgA1入血有关。本研究基于B细胞在诱导-效应部位间归巢现象，结合中医“脏腑相关（肺-大肠）理论”，围绕黏膜IgA应答动力学，探讨IgAN中医病机的现代科学内涵，为防治IgAN提供中医方法和理论支撑。

IgA nephropathy (IgAN) is the most important primary glomerular disease, multiple evidences suggest that mucosal immune abnormalities lead to increased galactose-deficient IgA1 (GD-IgA1) into the blood circulation is directly related to the pathogenesis of IgA nephropathy; excessive secretion of secretory IgA1 and IgA+B cell mistakenly homing to bone marrow is a source of GD-IgA1; BAFF and its receptor TACI play a key role in the above-described non-T cell-dependent B cell maturation and transformation to the secretory IgA class. We observed that IgAN patients showed "wind-heat, damp-heat" syndrome due to "mucosal infection" symptoms, and were associated with GD-IgA1 levels. Yiqi QingJie Recipe can significantly alleviate symptoms and improve prognosis. Based on this, we presumed “Qi deficiency of Lung and Spleen，defensive non-solid, rheumatic and damp-heat poisonous impairing kidney” is the pathogenesis of IgAN. The mechanism of Yiqi QingJie Recipe may be related to the regulation of BAFF-TACI signal, the reduction of IgA secretory cell overproduction and misplaced homing, and thus the reduction of GD-IgA1 blood. . This study is based on the homing phenomenon of B cells in the induction-effect site, combined with the "dirty-related (lung-large intestine) theory" of Chinese medicine, focused on the mucosal IgA response kinetics, to explore the modern scientific connotation of IgAN TCM pathogenesis, and to provide TCM treatment of IgAN and treatment method’s theoretical support.