Experimental poststreptococcal glomerulonephritis elicited by IgG Fc-binding M family proteins and blocked by IgG Fc fragment
Experimental poststreptococcal glomerulonephritis elicited by IgG Fc-binding M family proteins and blocked by IgG Fc fragment
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DOI：
10.1111/j.1600-0463.2011.02826.x
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发表时间：
2012-03-01
期刊：
影响因子：
2.8
通讯作者：
Totolian, Artem
中科院分区：
文献类型：
--
作者：
Burova, Larissa;Pigarevsky, Peter;Totolian, Artem
急性链球菌感染后肾小球肾炎（APSGN）是A组链球菌（GAS）咽喉或皮肤疾病的主要非化脓性并发症，其发病机制尚不清楚。近年来，基于某些链球菌细胞外因子以及链球菌和肾组织之间的免疫模拟的各种理论已经被提出。我们先前报道了许多临床GAS分离株具有致肾炎能力，显示单体或聚集IgG的非免疫结合。此外，在APSGN的兔模型中，我们获得了属于M家族表面蛋白的链球菌IgG Fc结合蛋白（IgGFcBPs）的重要作用的证据;因此，整个IgGFcBP阳性链球菌的超免疫显示诱导肾小球变化，IgG和补体C3沉积，类似于人类APSGN中记录的图片。这些典型的肾脏变化之前总是出现循环抗IgG抗体。在本工作中，使用相同的兔模型，发现从M22型GAS分离的两种纯化的IgGFcBP中的每一种引起与全细菌引起的肾小球变性损伤相当的肾小球变性损伤，以及抗IgG的形成。此外，i. v.施用纯化的人或兔IgG Fc片段，而不是Fab片段，支持Fc介导的机制在引起肾小球肾炎中的重要性。我们建议，抗IgG抗体，诱导链球菌IgGFcBP，促进肾脏积累的IgG含复合物，这反过来又引发补体沉积和促炎级联反应。对IgG Fc片段在APSGN中可能的有益作用的进一步研究应该是有意义的。
The pathogenesis of acute poststreptococcal glomerulonephritis (APSGN), a major nonsuppurative complication of group A streptococcal (GAS) throat or skin disease, remains unclear. During the years, various theories based on certain streptococcal extracellular factors, as well as immunological mimicry between streptococci and renal tissue, have been forwarded. We earlier reported that many clinical GAS isolates with documented nephritogenic capacity show non-immune binding of monomeric or aggregated IgG. Moreover, in a rabbit model of APSGN we obtained evidence for an important role of streptococcal IgG Fc binding proteins (IgGFcBPs) belonging to the M family surface proteins; thus, hyperimmunization by whole IgGFcBP-positive streptococci was shown to induce renal glomerular changes with deposition of IgG and complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by the appearance of circulating anti-IgG antibodies. In the present work, using the same rabbit model, each of two purified IgGFcBPs, isolated from type M22 GAS, were found to elicit glomerular degenerative damage comparable to that caused by whole bacteria, as well as formation of anti-IgG. In addition, the induction by whole streptococci (type M1) of experimental APSGN was inhibited by the i. v. administration of purified human or rabbit IgG Fc, but not Fab, fragment, supporting the importance of Fc-mediated mechanisms in causation of glomerulonephritis. We propose that anti-IgG antibody, induced by streptococcal IgGFcBP, facilitated renal accumulation of IgG-containing complexes, which in turn triggered complement deposition and proinflammatory cascades. Further studies on the possible beneficial effect of IgG Fc fragment in APSGN should be of interest.