Li Huixian, Lu Wanhong, Li Haiyun, Liu Xiaoling, Zhang Xue, Xie Liyi, Lan Ping, Yu Xiaoyang, Dai Yinjuan, Xie Xinfang, Lv Jicheng
Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
MOE Key Laboratory of Environment and Genes Related to Diseases, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
Front Pharmacol. 2021 Dec 16;12:793511. doi: 10.3389/fphar.2021.793511. eCollection 2021.
IgA nephropathy (IgAN) has a high degree of heterogeneity in clinical and pathological features. Among all subsets of IgAN, the pathogenesis of IgAN with minimal change disease (MCD-IgAN) remained controversial. We analyzed the clinical and pathological characteristics of MCD-IgAN patients in a retrospective cohort. Patients diagnosed with IgAN, excluding MCD-IgAN, were randomly selected as controls. Levels of plasma galactose-deficient IgA1 (GdIgA1), IgG autoantibodies against GdIgA1, GdIgA1 deposition in the glomerulus, and inflammatory reactivity of circulating poly-IgA1 complexes to cultured mesangial cells were evaluated. Patients with MCD-IgAN had significantly higher levels of proteinuria and estimated glomerular filtration rate (eGFR), lower levels of albumin and urine blood cells, and milder histological lesions by a light microscope compared to IgAN patients, which bears a resemblance to MCD. Lower levels of GdIgA1 (3.41 ± 1.68 vs. 4.92 ± 2.30 μg/ml, = 0.009) and IgG antiglycan autoantibodies (23.25 ± 22.59 vs. 76.58 ± 71.22 IU/ml, < 0.001) were found in MCD-IgAN patients than those in IgAN controls. Meanwhile, weaker fluorescence intensities of both IgA and GdIgA1 were observed in the glomerulus of MCD-IgAN patients compared to those in IgAN patients. Furthermore, poly-IgA1 complexes from MCD-IgAN patients induced weaker inflammatory effects on cultured mesangial cells than those from IgAN patients . The results demonstrated that MCD-IgAN cases represent a dual glomerulopathy, namely, mild IgAN with superimposed MCD, which furthermore provides substantial evidence for the corticosteroids therapy in MCD-IgAN patients as the guidelines recommended.
IgA肾病（IgAN）在临床和病理特征上具有高度异质性。在所有IgAN亚组中，微小病变型IgA肾病（MCD-IgAN）的发病机制仍存在争议。我们对一个回顾性队列中的MCD-IgAN患者的临床和病理特征进行了分析。将诊断为IgAN但排除MCD-IgAN的患者随机选为对照组。评估血浆半乳糖缺乏型IgA1（GdIgA1）水平、抗GdIgA1的IgG自身抗体、肾小球中GdIgA1沉积以及循环多聚IgA1复合物对培养的系膜细胞的炎症反应性。与IgAN患者相比，MCD-IgAN患者的蛋白尿水平和估计肾小球滤过率（eGFR）显著更高，白蛋白和尿血细胞水平更低，且光镜下组织学病变更轻，这与微小病变型肾病（MCD）相似。与IgAN对照组相比，MCD-IgAN患者的GdIgA1水平（3.41±1.68 vs. 4.92±2.30μg/ml，P = 0.009）和IgG抗聚糖自身抗体水平（23.25±22.59 vs. 76.58±71.22 IU/ml，P < 0.001）更低。同时，与IgAN患者相比，MCD-IgAN患者肾小球中IgA和GdIgA1的荧光强度均较弱。此外，MCD-IgAN患者的多聚IgA1复合物对培养的系膜细胞诱导的炎症作用比IgAN患者的更弱。结果表明，MCD-IgAN病例代表一种双重肾小球病，即轻度IgAN叠加MCD，这进一步为指南推荐的MCD-IgAN患者使用糖皮质激素治疗提供了充分证据。
