Table_1_Urinary complement profile in IgA nephropathy and its correlation with the clinical and pathological characteristics.docx

Background and objectivesThe activated complement profile in IgA nephropathy (IgAN) is still unclear. Our study investigated the profile of urinary complements in IgAN patients and its correlations with clinical and pathological characteristics.MethodsUrinary protein abundance was detected by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in 50 IgAN, 50 membranous nephropathy (MN), and 68 healthy controls (HC). Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify differentially expressed proteins in IgAN patients. The differentially expressed complement proteins were screened in IgAN patients, and their correlations with laboratory or pathological parameters were analyzed. Thereafter, 7 complement components were validated by enzyme-linked immunosorbent assay (ELISA) in the urine samples of 45 IgAN patients.ResultsThere were 786 differentially expressed proteins between IgAN and HC. KEGG analysis showed that differentially expressed urinary proteins in IgAN were enriched with complement. Of these, 67% of urinary complement protein abundance was associated with the estimated glomerular filtration rate. The urinary complement-related protein collectin12 (colec12), complement H factor (CFH), complement H factor-related protein 2 (CFHR2), and complement B factor (CFB) were positively correlated with serum creatinine; colec12, CFHR2, CFB, and C8g were positively correlated with glomerulosclerosis; CFH, CFHR2, C8g, and C9 were positively correlated with tubular atrophy/interstitial fibrosis.ConclusionAbnormally increased components of complement pathways significantly correlate with reduced renal function, proteinuria, and renal histological damage in IgAN. It could provide a potential biomarker panel for monitoring IgAN and provide clues for therapeutic choice targeting complement system of IgAN patients.

背景与目标：IgA肾病（IgAN）中激活的补体谱尚不明确。本研究旨在探讨IgAN患者尿液中补体谱及其与临床和病理特征的相关性。方法：通过液相色谱串联质谱法（LC–MS/MS）检测了50例IgAN、50例膜性肾小球肾炎（MN）和68例健康对照（HC）的尿液蛋白质丰度。随后，通过基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，识别了IgAN患者中差异表达的蛋白质。在IgAN患者中筛选了差异表达的补体蛋白，并分析了其与实验室或病理参数的相关性。之后，通过酶联免疫吸附测定（ELISA）在45例IgAN患者的尿液样本中验证了7种补体成分。结果：在IgAN与HC之间发现了786种差异表达的蛋白质。KEGG分析显示，IgAN中差异表达的尿液蛋白质富集于补体。其中，67%的尿液补体蛋白丰度与估算的肾小球滤过率相关。尿液补体相关蛋白collectin12（colec12）、补体H因子（CFH）、补体H因子相关蛋白2（CFHR2）和补体B因子（CFB）与血清肌酐呈正相关；colec12、CFHR2、CFB和C8g与肾小球硬化呈正相关；CFH、CFHR2、C8g和C9与肾小管萎缩/间质纤维化呈正相关。结论：补体途径异常增加的成分与IgAN的肾功能降低、蛋白尿和肾脏组织学损伤显著相关。这可为监测IgAN提供潜在的生物标志物组合，并为针对IgAN患者补体系统的治疗方案选择提供线索。