Patients with Proliferative Lupus Nephritis Have Autoantibodies That React to Moesin and Demonstrate Increased Glomerular Moesin Expression.
Dawn J CasterErik A KorteMichael L MerchantJon B KleinMichelle T BaratiAmi JoglekarDaniel W WilkeySusan CoventryJessica HataBrad H RovinJohn B HarleyBahram Namjou-KhalesKenneth R McleishDavid W PowellPublished in: Journal of clinical medicine (2021)
Kidney involvement in systemic lupus erythematosus (SLE)-termed lupus nephritis (LN)-is a severe manifestation of SLE that can lead to end-stage kidney disease (ESKD). LN is characterized by immune complex deposition and inflammation in the glomerulus. We tested the hypothesis that autoantibodies targeting podocyte and glomerular cell proteins contribute to the development of immune complex formation in LN. We used Western blotting with SLE sera from patients with and without LN to identify target antigens in human glomerular and cultured human-derived podocyte membrane proteins. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified the proteins in the gel regions corresponding to reactive bands observed with sera from LN patients. We identified 102 proteins that were present in both the podocyte and glomerular samples. We identified 10 high-probability candidates, including moesin, using bioinformatic analysis. Confirmation of moesin as a target antigen was conducted using immunohistochemical analysis (IHC) of kidney biopsy tissue and enzyme-linked immunosorbent assay (ELISA) to detect circulating antibodies. By IHC, biopsies from patients with proliferative lupus nephritis (PLN, class III/IV) demonstrated significantly increased glomerular expression of moesin (p < 0.01). By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against moesin (p < 0.01). This suggests that moesin is a target glomerular antigen in lupus nephritis.
Keyphrases
- high glucose
- endothelial cells
- diabetic nephropathy
- systemic lupus erythematosus
- liquid chromatography tandem mass spectrometry
- poor prognosis
- end stage renal disease
- chronic kidney disease
- oxidative stress
- ejection fraction
- induced pluripotent stem cells
- south africa
- newly diagnosed
- ms ms
- stem cells
- rheumatoid arthritis
- high resolution
- mesenchymal stem cells
- dendritic cells
- cell therapy
- single cell
- immune response
- drug induced
- patient reported outcomes
- patient reported