Department of Pathology and Laboratory Medicine, The Ohio State University, Columbus, OH 43210, USA.
Mod Pathol. 2013 Jun;26(6):799-805. doi: 10.1038/modpathol.2012.237. Epub 2013 Jan 18.
Recent breakthrough findings revealed that most patients with idiopathic (primary) membranous glomerulonephritis have IgG4 antibodies to the phospholipase A2 receptor (PLA2R). These IgG4 antibodies can be detected in the glomerular immune complexes and they colocalize with PLA2R. In secondary forms of membranous glomerulonephritis, such IgG4 antibodies are absent or less prevalent. There are no studies addressing the IgG subclass distribution across different stages of membranous glomerulonephritis. During a 25-month period, we identified 157 consecutive biopsies with membranous glomerulonephritis with adequate tissue for light, immunofluorescence and electron microscopy. Of the 157 membranous glomerulonephritis cases, 114 were primary membranous glomerulonephritis and 43 were secondary membranous glomerulonephritis. We compared the intensity of IgG subclass staining (on a semiquantitative scale of 0 to 3+) and the IgG subclass dominance between primary and secondary membranous glomerulonephritis and between the different stages of membranous glomerulonephritis. In primary membranous glomerulonephritis most (76% of cases) were IgG4 dominant. In contrast, in secondary membranous glomerulonephritis IgG1 was dominant in 60% of biopsies (P=0.0018). Interestingly, in early stage (stage 1) primary membranous glomerulonephritis, IgG1 was the dominant IgG subclass (64% of cases); in all later stages IgG4 dominated (P=0.0493). It appears that there is an inverse relationship between the intensity of glomerular capillary IgG4 and C1q staining. In secondary forms of membranous glomerulonephritis (heterogeneous group with low case numbers), we did not find such associations. Our data indicate that in early stage membranous glomerulonephritis, antibody response is different from later stages, with IgG1 dominant deposits. It is possible that early on, antigens other than PLA2R have an important role, Alternately, there may be an IgG subclass switch in the antibody response with IgG4 taking over later as the dominant immunoglobulin.
最近的突破性发现表明，大多数特发性（原发性）膜性肾小球肾炎患者的 IgG4 抗体针对磷脂酶 A2 受体（PLA2R）。这些 IgG4 抗体可在肾小球免疫复合物中检测到，并且与 PLA2R 共定位。在继发性膜性肾小球肾炎中，这些 IgG4 抗体不存在或较少见。目前尚无研究探讨 IgG 亚类在膜性肾小球肾炎不同阶段的分布情况。在 25 个月的时间里，我们鉴定了 157 例连续的膜性肾小球肾炎活检，这些活检均有足够的组织进行光镜、免疫荧光和电子显微镜检查。在这 157 例膜性肾小球肾炎病例中，114 例为原发性膜性肾小球肾炎，43 例为继发性膜性肾小球肾炎。我们比较了原发性和继发性膜性肾小球肾炎以及膜性肾小球肾炎不同阶段之间 IgG 亚类染色强度（半定量评分 0-3+）和 IgG 亚类优势。在原发性膜性肾小球肾炎中，大多数（76%的病例）为 IgG4 优势。相比之下，在继发性膜性肾小球肾炎中，60%的活检 IgG1 占优势（P=0.0018）。有趣的是，在早期（1 期）原发性膜性肾小球肾炎中，IgG1 是优势 IgG 亚类（64%的病例）；在所有较晚阶段，IgG4 占优势（P=0.0493）。似乎肾小球毛细血管 IgG4 和 C1q 染色的强度之间存在反比关系。在继发性膜性肾小球肾炎（病例数较少的异质性组）中，我们没有发现这种关联。我们的数据表明，在早期膜性肾小球肾炎中，抗体反应与后期不同，IgG1 优势沉积。早期可能除了 PLA2R 以外的抗原起重要作用，或者抗体反应中存在 IgG 亚类转换，IgG4 后来成为优势免疫球蛋白。
