新月体IgA肾病是IgA肾病的一个重症类型，也是引起急进性肾炎的常见原因。IgA1铰链区存在5个O-糖结合位点，尽管该区域半乳糖缺失是引起IgA肾病发病的关键机制，但是IgA1沉积后如何引起广泛的新月体形成，目前仍然缺乏相关的研究。我们前期工作发现来自新月体IgA肾病病人血浆IgA1分子针对抗糖抗体的抗原性与非新月体IgA肾病存在显著的差异，并且其肾脏局部补体激活能力明显增强，这种抗原性差异与半乳糖缺失的IgA1水平无关，因此我们推测IgA1分子铰链区不同位点半乳糖缺失，即糖型的差异是改变IgA1分子抗原性、并增强其补体激活和致病性的原因。本研究中我们通过质谱分析鉴定新月体IgA肾病IgA1分子的特异型糖型，并体外合成该糖肽后免疫大鼠获取其单克隆抗体，用于该糖型的检测；进而通过体外补体激活试验以及体内观察该糖型与新月体及治疗反应的相关性，最终明确该糖型及其单克隆抗体致病性及临床应用价值。

Crescentic IgA nephropathy(IgAN) is a severe form of IgAN disease, and also one of the most common reason of rapidly progressive glomerulonephritis. Its pathogenesis is still unclear. Aberrantly glycosylated IgA1, with galactose (Gal)-deficient hinge region O-glycans (Gd-IgA1), and its anti-glycan autoantibodies play a pivotal role in IgAN. Our prior studies showed that the IgA1 from crescentic IgAN showed much different antigenicity to the anti-glycans, as compared to non-crescentic IgAN. This difference was not related to the Gal defficient levels of IgA1. Thus we hypothesize that the specific site of glycosylation defect (glycoforms) has influence its antigenicity with increased pathogenicity. In this study we aim to identify the specific glycoforms of IgA1 through activated ion-electron capture.dissociation mass spectrometric analysis, and then synthesize this glycopeptide in vitro. Rats are immunized with this peptide to obtain specific monoclonal antibody. Gd-IgA1 ELISA for specifically detecting this glycoform is consequently constructed to evaluate its relevance with the crescents forming in IgA nephropathy and also its association with patient prognosis. We also evaluate the complement activation of this specific glycoforms in vitro.