IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAVN) are related glomerular diseases characterized by marked similarities in immunological and histological findings. We herein performed a comparative proteomic analysis of glomerular proteins in IgAN and IgAVN. We used renal biopsy specimens from 6 IgAN patients without nephrotic syndrome (NS) (IgAN-I subgroup), 6 IgAN patients with NS (IgAN-II subgroup), 6 IgAVN patients with 0–8.0% of glomeruli with crescent formation (IgAVN-I subgroup), 6 IgAVN patients with 21.2–44.8% of glomeruli with crescent formation (IgAVN-II subgroup), 9 IgAVN patients without NS (IgAVN-III subgroup), 3 IgAVN patients with NS (IgAN-IV subgroup), and 5 control cases. Proteins were extracted from laser microdissected glomeruli and analyzed using mass spectrometry. The relative abundance of proteins was compared between groups. An immunohistochemical validation study was also performed. More than 850 proteins with high confidence were identified. A principal component analysis revealed a clear separation between IgAN and IgAVN patients and control cases. In further analyses, 546 proteins that were matched with ≥ 2 peptides were selected. The levels of immunoglobulins (IgA, IgG, and IgM), complements (C3, C4A, C5, and C9), complement factor H-related proteins (CFHR) 1 and 5, vitronectin, fibrinogen chains, and transforming growth factor-β inducible gene-h3 were higher (> 2.6 fold) in the IgAN and IgAVN subgroups than in the control group, whereas hornerin levels were lower (< 0.3 fold). Furthermore, C9 and CFHR1 levels were significantly higher in the IgAN group than in the IgAVN group. The abundance of some podocyte-associated proteins and glomerular basement membrane (GBM) proteins was significantly less in the IgAN-II subgroup than in the IgAN-I subgroup as well as in the IgAVN-IV subgroup than in the IgAVN-III subgroup. Among the IgAN and IgAVN subgroups, talin 1 was not detected in the IgAN-II subgroup. This result was supported by immunohistochemical findings. The present results suggest shared molecular mechanisms for glomerular injury in IgAN and IgAVN, except for enhanced glomerular complement activation in IgAN. Differences in the protein abundance of podocyte-associated and GBM proteins between IgAN and IgAVN patients with and without NS may be associated with the severity of proteinuria.

中文翻译：

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IgA肾病和IgA血管炎伴肾炎肾小球蛋白的比较蛋白质组学分析

IgA 肾病 (IgAN) 和 IgA 血管炎伴肾炎 (IgAVN) 是相关的肾小球疾病，其特征在于免疫学和组织学发现具有显着相似性。我们在此对 IgAN 和 IgAVN 中的肾小球蛋白进行了比较蛋白质组学分析。我们使用的肾活检标本来自 6 名无肾病综合征 (NS) 的 IgAN 患者（IgAN-I 亚组）、6 名 IgAN NS 患者（IgAN-II 亚组）、6 名具有 0-8.0% 肾小球新月体形成的 IgAVN 患者（IgAVN- I 亚组），6 名 IgAVN 患者有 21.2-44.8% 的肾小球新月体形成（IgAVN-II 亚组），9 名 IgAVN 患者没有 NS（IgAVN-III 亚组），3 名 IgAVN 患者有 NS（IgAN-IV 亚组），和 5控制案例。从激光显微切割的肾小球中提取蛋白质，并使用质谱法进行分析。比较组间蛋白质的相对丰度。还进行了免疫组织化学验证研究。鉴定出超过 850 种具有高置信度的蛋白质。主成分分析揭示了 IgAN 和 IgAVN 患者与对照病例之间的明显分离。在进一步分析中，选择了与 ≥ 2 个肽匹配的 546 种蛋白质。免疫球蛋白（IgA、IgG 和 IgM）、补体（C3、C4A、C5 和 C9）、补体因子 H 相关蛋白 (CFHR) 1 和 5、玻连蛋白、纤维蛋白原链和转化生长因子-β 诱导因子的水平gene-h3 在 IgAN 和 IgAVN 亚组中比在对照组中更高（> 2.6 倍），而 hornerin 水平较低（< 0.3 倍）。此外，IgAN 组的 C9 和 CFHR1 水平显着高于 IgAVN 组。一些足细胞相关蛋白和肾小球基底膜 (GBM) 蛋白的丰度在 IgAN-II 亚组中明显低于 IgAN-I 亚组，在 IgAVN-IV 亚组中明显低于 IgAVN-III 亚组。在 IgAN 和 IgAVN 亚组中，talin 1 在 IgAN-II 亚组中未检测到。这一结果得到了免疫组织化学发现的支持。目前的结果表明 IgAN 和 IgAVN 中肾小球损伤的共同分子机制，除了 IgAN 中增强的肾小球补体激活。伴有和不伴有 NS 的 IgAN 和 IgAVN 患者足细胞相关蛋白和 GBM 蛋白的蛋白质丰度差异可能与蛋白尿的严重程度有关。