Barratt J, Bailey E M, Buck K S, Mailley J, Moayyedi P, Feehally J, Turney J H, Crabtree J E, Allen A C
Department of Nephrology, Leicester General Hospital, Leicester, UK, USA.
Am J Kidney Dis. 1999 Jun;33(6):1049-57. doi: 10.1016/S0272-6386(99)70141-1.
Numerous studies in the literature report aberrant immune responsiveness in immunoglobulin A (IgA) nephropathy. However, all these studies investigate immune responses invoked by an artificially engineered antigen challenge. For the first time in IgA nephropathy, we report the systemic humoral responses generated as part of an active mucosal immune response against a common environmental pathogen, Helicobacter pylori (Hp). We studied 22 patients with IgA nephropathy and 9 controls without renal disease who were shown to be infected with Hp, using a 13C-urea breath test. Hp antigen-specific enzyme-linked immunosorbent assays were established to measure the anti-Hp IgA, IgG, and IgA and IgG subclass antibody levels. In addition, anti-Hp responses in the monomeric and polymeric (pIgA) fractions of serum IgA were measured after separation by gel filtration high-performance liquid chromatography. IgA nephropathy was associated with both a greater rate of IgA anti-Hp seropositivity (P < 0.05) and a more pronounced IgA anti-Hp antibody response (P < 0.01). In almost all cases, IgA anti-Hp was IgA1, and more than 90% was polymeric. There was no difference in the frequency of IgG anti-Hp seropositivity, but patients produced a much greater IgG anti-Hp response (P < 0.01). In addition, the IgG subclass responses were markedly different, with IgG1 predominant in controls and IgG2 and IgG3 the major subclasses produced in IgA nephropathy. We have shown an exaggerated systemic antibody response to mucosal infection caused by Hp in patients with IgA nephropathy, predominantly consisting of pIgA1, IgG2, and IgG3. This suggests that in IgA nephropathy, not only is pIgA1 production poorly controlled, but regulation of IgG isotype switching in response to mucosal pathogens is also deranged.
文献中的众多研究报告了免疫球蛋白A（IgA）肾病中异常的免疫反应性。然而，所有这些研究都调查了人工设计的抗原刺激所引发的免疫反应。在IgA肾病研究中，我们首次报告了作为针对常见环境病原体幽门螺杆菌（Hp）的活跃黏膜免疫反应一部分而产生的全身体液反应。我们使用13C-尿素呼气试验研究了22例IgA肾病患者和9例无肾脏疾病且被证明感染Hp的对照者。建立了Hp抗原特异性酶联免疫吸附测定法来测量抗Hp IgA、IgG以及IgA和IgG亚类抗体水平。此外，通过凝胶过滤高效液相色谱分离后，测量血清IgA单体和多聚体（pIgA）部分中的抗Hp反应。IgA肾病与更高的IgA抗Hp血清阳性率（P < 0.05）以及更明显的IgA抗Hp抗体反应（P < 0.01）相关。在几乎所有病例中，IgA抗Hp为IgA1，且超过90%为多聚体。IgG抗Hp血清阳性频率没有差异，但患者产生的IgG抗Hp反应要大得多（P < 0.01）。此外，IgG亚类反应明显不同，对照组中以IgG1为主，而在IgA肾病中产生的主要亚类是IgG2和IgG3。我们已经表明，IgA肾病患者对Hp引起的黏膜感染存在过度的全身抗体反应，主要由pIgA1、IgG2和IgG3组成。这表明在IgA肾病中，不仅pIgA1的产生控制不佳，而且对黏膜病原体的IgG同种型转换调节也紊乱。
