Department of Nephrology (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310007, China.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Eur J Med Res. 2022 Aug 11;27(1):147. doi: 10.1186/s40001-022-00779-9.
This study aimed to analyze the distribution of IgG subclass in diabetic nephropathy (DN) and its association with clinicopathological features.
This is a single-center retrospective study enrolling 108 patients with biopsy-proven DN. Immunofluorescence and immunohistochemistry staining were applied, and clinicopathological features and renal outcomes were compared between patients with different patterns or categories of IgG subclass deposition.
Both IgG and its subclasses colocalized with collagen IV α5 on glomerular basement membrane (GBM) and some of tubular basement membrane (TBM). IgG1 and the Mixed type were two predominant types of deposition, no matter on GBM or TBM, and IgG1 showed a much higher deposition rate on GBM than that on TBM (P = 0.004). IgG subclass deposit on multi-location was more associated with a shorter duration of nephropathy and severer tubular interstitial injury (P < 0.05). The mixed type of IgG subclass deposit on GBM was merely associated with higher levels of proteinuria, whereas the deposition on TBM was more associated with higher levels of proteinuria, lower levels of albumin, more KIM-1 positive area, and thicker TBM (P < 0.05). Survival analysis revealed that none of the pattern or the category of IgG subclass deposit was a risk factor or a renal outcome indicator.
IgG subclass was selectively deposited along GBM and/or TBM in DN, and the mixed type of IgG subclass deposition on TBM had more clinical significance than the isotype and that on GBM. IgG subclass deposition is merely a manifestation or a consequence rather than a cause in DN.
本研究旨在分析糖尿病肾病（DN）中 IgG 亚类的分布及其与临床病理特征的关系。
这是一项单中心回顾性研究，纳入了 108 例经活检证实的 DN 患者。应用免疫荧光和免疫组化染色，比较不同 IgG 亚类沉积模式或类别患者的临床病理特征和肾脏结局。
IgG 及其亚类与肾小球基底膜（GBM）上的胶原 IV α5 以及部分肾小管基底膜（TBM）共定位。在 GBM 和 TBM 上，IgG1 和混合类型都是两种主要的沉积类型，且 IgG1 在 GBM 上的沉积率明显高于 TBM（P=0.004）。多部位 IgG 亚类沉积与肾病病程较短和肾小管间质损伤较重更相关（P<0.05）。GBM 上 IgG 亚类混合沉积类型仅与蛋白尿水平较高相关，而 TBM 上的沉积与蛋白尿水平较高、白蛋白水平较低、更多的 KIM-1 阳性面积和更厚的 TBM 相关（P<0.05）。生存分析显示，IgG 亚类沉积模式或类别均不是肾脏结局的风险因素。
在 DN 中，IgG 亚类选择性沉积于 GBM 和/或 TBM，TBM 上的 IgG 亚类混合沉积类型比其他类型具有更重要的临床意义。IgG 亚类沉积只是 DN 的一种表现或后果，而不是原因。
