Alaiya Ayodele, Assad Lina, Alkhafaji Dania, Shinwari Zakia, Almana Hadeel, Shoukri Mohamed, Alkorbi Lutfi, Ibrahim Hossamaldin Galal, Abdelsalam Mohamed Said, Skolnik Edward, Adra Chaker, Albaqumi Mamdouh
Proteomics Unit, Stem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Nephrol Dial Transplant. 2015 Jan;30(1):62-70. doi: 10.1093/ndt/gfu215. Epub 2014 Jun 9.
There have been several attempts to standardize the definition and increase reproducibility in classifying lupus nephritis (LN). The last was made by the International Society of Nephrology and Renal Pathology Society in 2003 where the introduction of Class IV subcategories (global and segmental) was introduced.
We investigated whether this subdivision is important using a proteomics approach. All patients with renal biopsies along with their clinical outcome of LN were identified and regrouped according to the above 2003 classifications. Fresh-frozen renal biopsies of Class IV LN (global and segmental), antineutrophil cytoplasmic antibody-associated vasculitis and normal tissue were analyzed using two-dimensional gel electrophoresis (2-DE) and mass spectrometry. Differentially expressed proteins were identified and subjected to principal component analysis (PCA), and post hoc analysis for the four sample groups.
PCA of 72 differentially expressed spots separated Class IV global and Class IV segmental from both normal and antineutrophil cytoplasmic antibody-associated vasculitis (ANCA). The 28 identified proteins were used in a post hoc analysis, and showed that IV-global and IV-segmental differ in several protein expression when compared with normal and ANCA. To confirm the proteomic results, a total of 78 patients (50 Class IV-Global and 28 Class IV-Segmental) were re-classified according to 2003 classification. There was no difference in therapy between the groups. The renal survival and patient survivals were similar in both groups.
There is no strong evidence to support a different outcome between the two subcategories of Class-IV LN and, they should thus be treated the same until further studies indicate otherwise.
为使狼疮性肾炎（LN）的定义标准化并提高其分类的可重复性，已经进行了多次尝试。最近一次尝试是由国际肾脏病学会和肾脏病理学会在2003年进行的，当时引入了IV类亚分类（弥漫性和节段性）。
我们使用蛋白质组学方法研究这种细分是否重要。确定了所有接受肾活检的患者及其LN的临床结局，并根据上述2003年分类重新分组。使用二维凝胶电泳（2-DE）和质谱分析IV类LN（弥漫性和节段性）、抗中性粒细胞胞浆抗体相关性血管炎和正常组织的新鲜冷冻肾活检标本。鉴定差异表达的蛋白质，并进行主成分分析（PCA）以及对四个样本组的事后分析。
72个差异表达斑点的PCA将IV类弥漫性和IV类节段性与正常组织和抗中性粒细胞胞浆抗体相关性血管炎（ANCA）区分开来。28种鉴定出的蛋白质用于事后分析，结果显示与正常组织和ANCA相比，IV-弥漫性和IV-节段性在几种蛋白质表达上存在差异。为了证实蛋白质组学结果，根据2003年分类对总共78例患者（50例IV-弥漫性和28例IV-节段性）进行了重新分类。两组之间的治疗无差异。两组的肾脏存活率和患者存活率相似。
没有强有力的证据支持IV类LN的两个亚分类之间存在不同的结局，因此在进一步研究表明并非如此之前，应将它们同等对待。
