Abstract
INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic inflammatory condition with multisystem involvement. One of the key features of the disease is the upregulation of type I interferons, resulting in the so-called "interferon signature". Recent flow cytometric and transcriptomic studies identified Sialoadhesin (Sn, CD169) as an important interferon-induced blood monocyte biomarker in diseased patients. To investigate a potential causative role of Sn in SLE, we generated NZBWF1 (New Zealand Black x New Zealand White F1) mice lacking Sn and compared onset and progression of disease with NZBWF1 expressing normal levels of Sn. METHODS: Sn expression in renal tissues of pre-diseased and diseased NZBWF1 mice was evaluated by Quantitative real time PCR (QPCR) and immunohistochemistry. Sn-/- NZBWF1 mice were generated by speed congenics. Disease severity of Sn+/+ and Sn-/- NZBWF1 mice was assessed by serum immunoassays, flow cytometry, light microscopy and immunohistochemistry. RESULTS: Renal tissues from proteinuric NZBWF1 mice exhibited a significant upregulation of Sn mRNA and protein expression following disease onset. Further immunohistochemical analysis showed that Sn+ macrophages assumed a distinct periglomerular distribution and, unlike CD68+ macrophages, were not present within the glomeruli. Analysis of disease severity in Sn-/- and Sn+/+ NZBWF1 mice revealed no significant differences in the disease progression between the two groups although Sn-deficient mice showed a more rapid onset of proteinuria. CONCLUSIONS: These data confirm a positive correlation of Sn with disease activity. However, Sn deficiency does not have a significant effect on the severity and progression of lupus nephritis in the NZBWF1 mouse model.