High renal DC-SIGN+ cell density is associated with severe renal lesions and poor prognosis in patients with immunoglobulin A nephropathy

Abstract

Background and aims: In this observational cohort study, we assessed the prognostic value of DC-SIGN⁺ cells in the pathogenesis and progression of IgA nephropathy (IgAN).

Methods and results: A total of 139 adult IgAN patients were enrolled into this study from June 2009 to June 2010. We characterised DC-SIGN⁺ cells by immunohistochemistry or immunofluorescence in renal biopsy tissue. Correlations between the DC-SIGN, intercellular adhesion molecule 3 (ICAM-3), CD4 and CD8 were evaluated. Patients were classified into the DC-SIGN^high and DC-SIGN^low groups. Depending on an average of 100-month follow-up, the predictive value of DC-SIGN⁺ cells in IgAN progression was analysed. DC-SIGN⁺ cells were found frequently in IgAN kidneys while rarely observed in normal kidneys, and almost all DC-SIGN⁺ cells expressed MHC-II. We also found that DC-SIGN⁺ cells were adjacent to ICAM-3-positive CD4⁺ and CD8⁺ lymphocytes. The density of DC-SIGN⁺ cells was positively and linearly correlated with the density of ICAM-3⁺ cells, CD4⁺ cells and CD8⁺ cells in renal biopsy tissues. In the DC-SIGN^high group, the degree of renal lesion and inflammatory cell infiltration was more severe compared to the DC-SIGN^low group. Patients in the DC-SIGN^high group also had increased incidences of deteriorating renal function during the follow up compared to patients in the DC-SIGN^low group.

Conclusions: DC-SIGN⁺ cells probably served as a potential contributor to exacerbate local inflammatory response. The density of DC-SIGN⁺ cells was associated with the severity of renal lesions of the patients. High renal DC-SIGN⁺ cell density might be used as a predictor of poor prognosis in patients with IgAN.

Keywords: DC-SIGN; ICAM-3; IgA nephropathy; dendritic cells; lymphocytes.