Divisions of Nephrology and Immunology, RWTH University of Aachen, Pauwelstrasse 30, D 52057 Aachen, Germany.
The John Walls Renal Unit, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
Nat Rev Nephrol. 2016 Mar;12(3):147-56. doi: 10.1038/nrneph.2015.208. Epub 2015 Dec 30.
Links between IgA nephropathy (IgAN) and the mucosa have been recognized since the 1970s. In particular, the observation of visible haematuria induced by respiratory infections in patients with IgAN and the association of IgAN with diseases in which the mucosa plays a part, especially coeliac disease, have been taken as evidence of a mucosa-kidney axis. Here, we review current evidence that links the mucosa, in particular the gastrointestinal mucosa, and IgA produced by the bone marrow with IgAN. Genome-wide association studies in patients with IgAN have identified risk loci in genes involved in the intestinal mucosal integrity and immune network. Furthermore, the systemic immune response to mucosal antigens in IgAN is increased. Moreover, patients with IgAN have an increased reactivity to dietary proteins associated with subclinical intestinal mucosal inflammation. Associations between IgAN and gastrointestinal diseases have also been reported in a small number of patients, but whether these diseases share a common pathogenesis or whether gastrointestinal inflammation exacerbates IgAN is uncertain. Indeed, mucosal alterations such as infections could activate the innate immune system, aggravate a pre-existing IgAN and promote disease manifestations such as macrohaematuria. Various clinical interventions and trials targeting the mucosa or presumed mucosa-associated mechanisms have so far not yielded consistent findings and the results of ongoing trials are eagerly awaited.
自 20 世纪 70 年代以来，人们就已经认识到 IgA 肾病（IgAN）与黏膜之间存在联系。特别是，在 IgAN 患者中观察到由呼吸道感染引起的肉眼血尿，以及 IgAN 与黏膜起作用的疾病之间的关联，特别是乳糜泻，被认为是黏膜-肾脏轴的证据。在这里，我们回顾了将黏膜（特别是胃肠道黏膜）和骨髓产生的 IgA 与 IgAN 联系起来的现有证据。在 IgAN 患者中进行的全基因组关联研究已经确定了涉及肠道黏膜完整性和免疫网络的基因中的风险位点。此外，IgAN 患者对黏膜抗原的全身免疫反应增加。此外，IgAN 患者对与亚临床肠道黏膜炎症相关的膳食蛋白的反应性增加。在少数患者中也报道了 IgAN 与胃肠道疾病之间的关联，但这些疾病是否具有共同的发病机制，或者胃肠道炎症是否会加重 IgAN 尚不确定。事实上，黏膜改变（如感染）可能会激活先天免疫系统，加重已存在的 IgAN 并促进肉眼血尿等疾病表现。迄今为止，针对黏膜或假定的黏膜相关机制的各种临床干预和试验并未产生一致的结果，正在进行的试验的结果备受期待。
