Establishment of a Mouse IgA Nephropathy Model With the MBP‐20‐Peptide Fusion Protein

Abstract

Here, we aimed to determine whether immunoglobulin-A nephropathy (IgAN) could be induced in Balb/c mice by immunizing them with a fusion protein (MBP-20 peptide) comprising the maltose-binding protein (MBP) and a 20-amino-acid peptide derived from Staphylococcus aureus. A recombinant plasmid encoding the fusion protein was constructed and expressed in bacterial cells. The synthetic 20-peptide was used to prepare the monoclonal antibody. Balb/c mice were immunized with the MBP-20-peptide fusion protein over a 21-week course before renal histology was examined at the light and electron microscopic levels. Direct immunofluorescence staining with the anti-20-peptide monoclonal antibody was also performed using renal biopsy tissue from human IgAN patients as a comparison. IgA and IgG specific for the 20-peptide in human and mice serum were detected. The IgAN experimental mice developed a clinical and pathological profile that closely resembled that of human IgAN patients, including the induction of hematuria and numerous histopathological features. Levels of IgA and IgG specific for the 20-peptide were significantly increased in serum from the IgAN experimental mice and IgAN patients compared with control mice and non-IgAN patients. In IgAN model mice, the anti-20-peptide antibody labeled glomeruli, while the antibody strongly labeled glomeruli and weakly labeled tubular epithelial cells in renal tissue from human IgAN patients. In conclusion, immunization with an MBP-20-peptide fusion protein is able to induce clinical and pathological features closely resembling IgAN in Balb/c mice, indicating a potentially useful role for the model in the study of IgAN and related diseases. Anat Rec, 293:1729Rec, 293: -1737

Comparison of clinicopathological features between children and adults with IgA nephropathy

“…However, some studies indicate that URI, particularly tonsillitis and pharyngitis, might be related to IgAN [6,8,9,[20][21][22]. Similar findings also appeared in this study.…”

“…Gross hematuria or deteriorated urinary findings following an episode of upper respiratory infection (URI) have been observed in many patients with IgAN, most commonly during childhood and with younger patients [6,7]. Furthermore, tonsillectomy is effective for some IgAN patients and Staphylococcus aureus antigens have been found to induce IgAN in Balb/c mice [6,8,9]. However, no study has reported the clinicopathological differences between URItriggered IgAN patients and other patients.…”

Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy

“…However, no other endogenous or exogenous molecules that can affect HMCs have been reported. In our present study, we conducted further in vitro research based on our previous study of an IgAN animal model [39]. We concluded that pGSN and Gd-IgA1 have a synergistic effect on the mechanism of renal fibrosis in IgAN, and this effect is achieved through the TGF-β1/Smads signaling pathway.…”

The Influence and Role of Microbial Factors in Autoimmune Kidney Diseases: A Systematic Review

“…Immunization with a maltose-binding protein and a 20-amino acid peptide derived from Staphylococcus aureus was also capable of inducing an IgA nephropathy like phenotype. Furthermore, anti-20-peptide antibodies labelled glomeruli of patients with IgA nephropathy [ 59 ] ( Table 3 ).…”