血清异常糖基化IgA1在40例IgA肾病诊断中的应用价值研究
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摘要
目的探讨血清异常糖基化IgA1 (Gd-IgA1)在IgA肾病诊断中的价值,及其与肾功能损伤程度、肾脏病理改变之间的联系。方法收集2016年1月至2017年12月于中国医科大学附属盛京医院行肾脏病理诊断的IgA肾病患者40例(A组)、其他类型原发性肾小球肾炎患者20例(B组)以及20名健康体检者(C组)的血清,检测所有血清样本中Gd-IgA1水平及A、B组患者24 h尿蛋白定量、血清肌酐,计算e GFR,记录肾组织病理类型及Lee氏分级结果。通过绘制ROC曲线并计算曲线下面积,研究血清Gd-IgA1在诊断IgA肾病中的价值。结果 IgA肾病患者血清Gd-IgA1明显高于其他类型原发性肾小球疾病组和健康对照组,ROC曲线下面积为0.886,血清Gd-IgA1高于662.5 U/mL时提示存在IgA肾病可能,且血清Gd-IgA1水平与IgA肾病患者肾功能损伤程度及肾脏病理改变存在一定关系。结论对于不能进行肾脏病理检查的患者,检测血清Gd-IgA1水平对诊断IgA肾病有一定意义。
Objective To investigate the value of serum galactose-deficient IgA1 in the diagnosis of IgA nephropathy and explore its relationship with the decline of renal function and pathological grade of renal biospy samples of the patients. Methods The serum samples were collected from, Shengjing Hospital of China Medical Unerversity from January 2016 to December 2017,which included 40 IgA nephropathy patients(group A), 20 other primary glomerulonephritis patients(group B) and 20 healthy persons(group C).Serum levels of GD-IgA1 were detected in all the samples.The 24-hour urinary protein and serum creatinine were measured in group A and B,the eGFR calculated. Recorded the pathological grade of renal biospy samples and Lee's classification. Study the value of serum Gd-IgA1 level in diagnosing IgA nephropathy by drawing ROC curve and calculating the area under the curve. Results The serum levels of GdIgA1 in IgA nephropathy patients were significantly higher than those in other types of primary glomerular diseases and healthy controls.The area under ROC curve was 0.886.When serum Gd-IgA1 level is higher than 662.5 U/ml, it suggested that people were more likely to have a IgA nephropathy.The level of serum Gd-IgA1 was related to the decline of renal function and pathological grade of renal biospy samples in patients with IgA nephropathy. Conclusion Serum Gd-IgA1 levels may be helpful in the diagnosis of IgA nephropathy in patients who can not undergo renal pathological examination.
Objective To investigate the value of serum galactose-deficient IgA1 in the diagnosis of IgA nephropathy and explore its relationship with the decline of renal function and pathological grade of renal biospy samples of the patients. Methods The serum samples were collected from, Shengjing Hospital of China Medical Unerversity from January 2016 to December 2017,which included 40 IgA nephropathy patients(group A), 20 other primary glomerulonephritis patients(group B) and 20 healthy persons(group C).Serum levels of GD-IgA1 were detected in all the samples.The 24-hour urinary protein and serum creatinine were measured in group A and B,the eGFR calculated. Recorded the pathological grade of renal biospy samples and Lee's classification. Study the value of serum Gd-IgA1 level in diagnosing IgA nephropathy by drawing ROC curve and calculating the area under the curve. Results The serum levels of GdIgA1 in IgA nephropathy patients were significantly higher than those in other types of primary glomerular diseases and healthy controls.The area under ROC curve was 0.886.When serum Gd-IgA1 level is higher than 662.5 U/ml, it suggested that people were more likely to have a IgA nephropathy.The level of serum Gd-IgA1 was related to the decline of renal function and pathological grade of renal biospy samples in patients with IgA nephropathy. Conclusion Serum Gd-IgA1 levels may be helpful in the diagnosis of IgA nephropathy in patients who can not undergo renal pathological examination.
引文
[1]Soares MFS, Roberts ISD. Histologic classification of IgA nephropathy:Past, Present, and Future[J]. Semin Nephrol, 2018, 38(5):477-484.
[2]Al-Eisa A, Dhaunsi GS. IgA enhances IGF-1 mitogenic activity via receptormodulationinglomerularmesangialcells:implications forIgA-inducednephropathy[J].KidneyBloodPressRes,2017,42(3):391-397.
[3]程媛,樊均明. IgA1异常糖基化在IgA肾病发病机制中的研究进展[J].中国中西医结合肾病杂志, 2009, 10(10):921-923.
[4]Inker LA, Mondal H, Greene T, et al. Early change in urine protein as a surrogate end point in studies of IgA nephropathy:an individualpatient meta-analysis[J]. Am J Kidney Dis, 2016, 68(3):392-401.
[5]SmithAC,MolyneuxK,FeehallyJ,etal.O-glycosylationof serum IgA1 antibodies against mucosal and systemic antigens in IgA nephropathy[J]. J Am Soc Nephrol, 2006, 17(12):3520-3528.
[6]SuzukiH,MoldoveanuZ,HallS,etal.IgA1secretingcelllines from patients with IgA nephropathy produce aberrantly glycosylated IgA1[J]. J Clin Invest, 2008, 118(2):629-639.
[7]Ma YC, Zuo L, Chen JH, et al. Modified glomerular filtration rate estimatingequationforChinesepatientswithchronickidney disease[J]. J Am Soc Nephrol, 2006, 17(10):2937-2944.
[8]Nasri H, Mubarak M. Extracapillary proliferation in IgA nephropathy;recent findings and new ideas[J]. J Nephropathol, 2015, 4(1):1-5.
[9]Hotta O, Furuta T, Chiba S, et al. Regression of IgA nephropathy:a repeat biopsy study[J]. Am J Kidney Dis, 2002, 39(3):493-502.
[10]Tomana M, Novak J, Julian BA, et al. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactosedeficient hinge region and antiglycan antibodies[J]. J Clin Invest,1999, 104(1):73-81.
[11]Lehoux S, Mi R, Aryal RP, Wang Y, et al. Identification of distinct glycoforms of IgA1 in plasma from patients with immunoglobulin A(IgA)nephropathy and healthy individuals[J]. Mol Cell Proteomics,2014, 13(11):3097-113.
[12]ShimizuA,TakeiT,MoriyamaT,etal.Clinicalandpathological studies of IgA nephropathy presenting as a rapidly progressive form of glomerulonephritis[J]. Intern Med, 2013, 52(22):2489-94.
[13]燕宇,徐丽霞,张军军,等.糖基化异常IgA1自身聚合或与IgG形成的大分子可能与IgA肾病病理表型相关[J].中华微生物学和免疫学杂志, 2006, 26(10):898-903.
[14]CamillaR,SuzukiH,DapraV.Oxidativestressandgalactosedeficient IgA1 as markers of progression in IgA nephropathy[J]. Clin J Am Soc Nephrol, 2011, 6(8):1903-1911.
[15]Moura IC, Arcos FM, Sadaka C, et al. Glycosylation and size of IgA1are essential for interaction with mesangial transferring recept or in IgA nephropathy[J]. J Am Soc Nephrol, 2004,15(6):622-634.
[16]McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide:a systematic review of the literature[J].Nephrol Dial Transplant, 2011, 26(4):414-430.
[17]Berthoux F, Suzuki H, Thibaudin L, et al. Autoantibodies targeting galactose-def icientIg A1associatew ithprogressionofIg A nephropathy[J]. J Am Soc Nephrol, 2012, 23(9):1579-1587.
[18]Moldoveanu Z, Wyatt RJ, Lee JY, et al. Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels[J]. Kidney Int,2007, 71(11):1148-1154.
[19]Kim MJ, Schaub S, Molyneux K, et al. Effect of immunosuppressive drugs on the changes of serum galactose-deficient IgA1 in patients with IgA nephropathy[J]. PLoS ONE, 2016, 11(12):e0166830.
[20]Kiryluk K, Moldoveanu Z, Sanders JT, et al. Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and HenochSch?nlein purpura nephritis[J]. Kidney Int, 2011, 80(1):79-87.
[21]芮艳霞,寿张飞.单中心IgA肾病高尿酸血症患病率及其临床病理特点分析[J].解放军医学杂志, 2016,41(6):518-520.
[22]李聚敏,周焕芝,邹万忠,等. IgA肾病伴IgG4相关性间质性肾炎1例报道[J].解放军医学杂志,2014,39(7):590-592.
[2]Al-Eisa A, Dhaunsi GS. IgA enhances IGF-1 mitogenic activity via receptormodulationinglomerularmesangialcells:implications forIgA-inducednephropathy[J].KidneyBloodPressRes,2017,42(3):391-397.
[3]程媛,樊均明. IgA1异常糖基化在IgA肾病发病机制中的研究进展[J].中国中西医结合肾病杂志, 2009, 10(10):921-923.
[4]Inker LA, Mondal H, Greene T, et al. Early change in urine protein as a surrogate end point in studies of IgA nephropathy:an individualpatient meta-analysis[J]. Am J Kidney Dis, 2016, 68(3):392-401.
[5]SmithAC,MolyneuxK,FeehallyJ,etal.O-glycosylationof serum IgA1 antibodies against mucosal and systemic antigens in IgA nephropathy[J]. J Am Soc Nephrol, 2006, 17(12):3520-3528.
[6]SuzukiH,MoldoveanuZ,HallS,etal.IgA1secretingcelllines from patients with IgA nephropathy produce aberrantly glycosylated IgA1[J]. J Clin Invest, 2008, 118(2):629-639.
[7]Ma YC, Zuo L, Chen JH, et al. Modified glomerular filtration rate estimatingequationforChinesepatientswithchronickidney disease[J]. J Am Soc Nephrol, 2006, 17(10):2937-2944.
[8]Nasri H, Mubarak M. Extracapillary proliferation in IgA nephropathy;recent findings and new ideas[J]. J Nephropathol, 2015, 4(1):1-5.
[9]Hotta O, Furuta T, Chiba S, et al. Regression of IgA nephropathy:a repeat biopsy study[J]. Am J Kidney Dis, 2002, 39(3):493-502.
[10]Tomana M, Novak J, Julian BA, et al. Circulating immune complexes in IgA nephropathy consist of IgA1 with galactosedeficient hinge region and antiglycan antibodies[J]. J Clin Invest,1999, 104(1):73-81.
[11]Lehoux S, Mi R, Aryal RP, Wang Y, et al. Identification of distinct glycoforms of IgA1 in plasma from patients with immunoglobulin A(IgA)nephropathy and healthy individuals[J]. Mol Cell Proteomics,2014, 13(11):3097-113.
[12]ShimizuA,TakeiT,MoriyamaT,etal.Clinicalandpathological studies of IgA nephropathy presenting as a rapidly progressive form of glomerulonephritis[J]. Intern Med, 2013, 52(22):2489-94.
[13]燕宇,徐丽霞,张军军,等.糖基化异常IgA1自身聚合或与IgG形成的大分子可能与IgA肾病病理表型相关[J].中华微生物学和免疫学杂志, 2006, 26(10):898-903.
[14]CamillaR,SuzukiH,DapraV.Oxidativestressandgalactosedeficient IgA1 as markers of progression in IgA nephropathy[J]. Clin J Am Soc Nephrol, 2011, 6(8):1903-1911.
[15]Moura IC, Arcos FM, Sadaka C, et al. Glycosylation and size of IgA1are essential for interaction with mesangial transferring recept or in IgA nephropathy[J]. J Am Soc Nephrol, 2004,15(6):622-634.
[16]McGrogan A, Franssen CF, de Vries CS. The incidence of primary glomerulonephritis worldwide:a systematic review of the literature[J].Nephrol Dial Transplant, 2011, 26(4):414-430.
[17]Berthoux F, Suzuki H, Thibaudin L, et al. Autoantibodies targeting galactose-def icientIg A1associatew ithprogressionofIg A nephropathy[J]. J Am Soc Nephrol, 2012, 23(9):1579-1587.
[18]Moldoveanu Z, Wyatt RJ, Lee JY, et al. Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels[J]. Kidney Int,2007, 71(11):1148-1154.
[19]Kim MJ, Schaub S, Molyneux K, et al. Effect of immunosuppressive drugs on the changes of serum galactose-deficient IgA1 in patients with IgA nephropathy[J]. PLoS ONE, 2016, 11(12):e0166830.
[20]Kiryluk K, Moldoveanu Z, Sanders JT, et al. Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and HenochSch?nlein purpura nephritis[J]. Kidney Int, 2011, 80(1):79-87.
[21]芮艳霞,寿张飞.单中心IgA肾病高尿酸血症患病率及其临床病理特点分析[J].解放军医学杂志, 2016,41(6):518-520.
[22]李聚敏,周焕芝,邹万忠,等. IgA肾病伴IgG4相关性间质性肾炎1例报道[J].解放军医学杂志,2014,39(7):590-592.
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