Abstract
BackgroundIgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases and might lead to end-stage kidney disease. Accurate and non-invasive biomarkers for early diagnosis are required for early intervention and consequent therapy for IgAN patients. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated.MethodsIn this study, we used urinary proteomics to discover candidate biomarkers of IgAN in patients of Uygur ethnicity. The urinary proteins from Uygur normal control and Uygur IgAN patients were extracted and analyzed using 2D-LC-MS/MS and isobaric tags for relative and absolute quantitation (iTRAQ) analysis.ResultsA total of 277 proteins were found to be differentially represented in Uygur IgAN compared with the respective normal controls. The bioinformatics analysis revealed that the immune response, cell survival, and complement system were activated in Uygur IgAN. Many differentially expressed proteins were found to be related to nephropathy and kidney injuries. Four candidate biomarkers were validated by Western blot, and these results were consistent with the iTRAQ results. ICAM1, TIMP1, SERPINC1 and ADIPOQ were upregulated in Uygur IgAN. Bioinformatic analysis revealed that the increase of ICAM1 and TIMP1 might be caused by IgAN, but the increase of SERPINC1 and ADIPOQ might be caused by proteinuria. SERPINC1 and ICAM1 were identified as the candidate biomarkers with excellent area-under-the-curve (AUC) values (0.84) for distinguishing Uygur IgAN from normal controls.ConclusionsUsing urinary proteomic analysis, we identified several candidate biomarkers for IgAN in patients of Uygur ethnicity. These results will prove helpful for exploring the pathological mechanism of IgAN in patients of Uygur ethnicity and for developing better treatments for these patients.
Highlights
IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases [1], and primary IgAN is characterized by the deposition of the IgA antibody in theThe urinary proteome can reflect alterations in the urinary system; urine is a suitable source for the discoveryGuo et al BMC Nephrology (2018) 19:358 of biomarkers of kidney diseases [6]
The urinary albumin excretion rates (UAER), serum creatinine (SCr) and blood urea nitrogen (BUN) levels were increased by 28-fold, 91 and 54%, respectively, and the estimated glomerular filtration rate (eGFR) and serum Alb levels were decreased significantly by 33 and 21%, respectively, in the Uygur IgAN group compared with the Uygur normal controls
The body mass index (BMI) index was increased in the Uygur IgAN patients
Summary
IgA nephropathy (IgAN) is one of the most common forms of idiopathic glomerular diseases [1], and primary IgAN is characterized by the deposition of the IgA antibody in theThe urinary proteome can reflect alterations in the urinary system; urine is a suitable source for the discoveryGuo et al BMC Nephrology (2018) 19:358 of biomarkers of kidney diseases [6]. Many publications have reported differentially expressed proteins in the urine, urinary exosomes and kidney tissue of IgAN patients using various proteomic methods, including MALDI-TOF [4, 7, 8], 2D-GEL [1], iTRAQ [9, 10], SILAC [11], and label-free quantification methods [12, 13]. The above-mentioned studies suggest that urinary proteomics could be used for the discovery of biomarkers of IgAN, and more accurate candidate urinary biomarkers for IgAN must be identified and validated. Because variance in the disease incidence and predisposing genes of IgAN has been detected among different ethnicities, the ethnicity factor should be considered in IgAN biomarker discovery. The differences in the protein profiles and pathological mechanisms of IgAN in patients of Uygur ethnicity need to be clearly illustrated
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