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Updated: Nov 24, 2025
Detection of MicroRNA Expression in the Kidneys of Immunoglobulin A Nephropathic Mice
Published on: July 8, 2020
Mass spectrometry-based screening identifies circulating immunoglobulinA-α1-microglobulin complex as potential
Boyang Xu1,2,3,4, Li Zhu1,2,3,4, Qingsong Wang5
1Department of Medicine, Renal Division, Peking University First Hospital, Beijing, China, and Peking University Institute of Nephrology, Beijing, China.
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.
