Mass spectrometry-based screening identifies circulating immunoglobulinA-α1-microglobulin complex as potential biomarker in immunoglobulin A nephropathy
| Autor: | Jicheng Lv, Bo-Yang Xu, Wenjia Lai, Jianguo Ji, Qingsong Wang, Li Zhu, Yanfeng Zhao, Sufang Shi, Meng Jia, Hong Zhang, Lijun Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunoglobulin A Adult Male Glycosylation Population 030232 urology & nephrology Renal function Enzyme-Linked Immunosorbent Assay urologic and male genital diseases Kidney Mass Spectrometry 03 medical and health sciences 0302 clinical medicine In vivo Alpha-Globulins Medicine Humans education Transplantation education.field_of_study biology Mesangial cell Beta-2 microglobulin business.industry Glomerular mesangium Glomerulonephritis IGA Glomerular Mesangium 030104 developmental biology Nephrology Immunology Mesangial Cells biology.protein business Alpha-1-microglobulin Biomarkers |
| Zdroj: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 36(5) |
| ISSN: | 1460-2385 |
| Popis: | Background Immunoglobulin A nephropathy (IgAN) is characterized by predominant IgA deposition in the glomerular mesangium. Previous studies have proved that renal-deposited IgA in IgAN came from circulating IgA1-containing complexes (CICs). Methods To explore the composition of CICs in IgAN, we isolated CICs from IgAN patients and healthy controls and then quantitatively analyzed them by mass spectrometry. Meanwhile, the isolated CICs were used to treat human mesangial cells to monitor mesangial cell injury. Using the protein content and injury effects, the key constituent in CICs was identified. Then the circulating levels of identified key constituent–IgA complex were detected in an independent population by an in-house-developed enzyme-linked immunosorbent assay. Results By comparing the proteins of CICs between IgAN patients and controls, we found that 14 proteins showed significantly different levels. Among them, α1-microglobulin content in CICs was associated with not only in vitro mesangial cell proliferation and monocyte chemoattractant protein 1 secretion, but also in vivo estimated glomerular filtration rate (eGFR) levels and tubulointerstitial lesions in IgAN patients. Moreover, we found α1-microglobulin was prone to bind aberrant glycosylated IgA1. Additionally, elevated circulating IgA-α1-microglobulin complex levels were detected in an independent IgAN population and IgA-α1-microglobulin complex levels were correlated with hypertension, eGFR levels and Oxford T- scores in these IgAN patients. Conclusions Our results suggest that the IgA-α1-microglobulin complex is an important constituent in CICs and that circulating IgA-α1-microglobulin complex detection might serve as a potential noninvasive biomarker detection method for IgAN. |
| Databáze: | OpenAIRE |
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