Lupus nephritis: correlation of immunohistochemical expression of C4d, CD163-positive M2c-like macrophages and Foxp3-expressing regulatory T cells with disease activity and chronicity

Abstract

Background C4d, which is a serum complement cleavage product of the activated complement component C4, was found to be an accurate indicator of lupus activity compared to complement levels. Recently, macrophages have been considered to be pivotal members in the pathogenesis of lupus nephritis (LN). M2c-like macrophages have anti-inflammatory functions and promote fibrosis. Multiple studies have detected that LN is associated with an imbalance between the regulatory T cell (Treg) population and the inflammatory T helper subtypes. Methods We evaluated and scored the immunohistochemical expression of C4d, CD163-positive M2C-macrophages and Foxp3-expressing Tregs in 53 renal biopsies of LN. Their expression was scored and correlated with clinical and histological disease activity and chronicity. Results Class IV was the most prevalent class (50.9%), followed by class III (17%). PTC-C4d intensity score, CD163% of positive M2c macrophages and FOXP3% of positive Tregs were significantly correlated with chronicity index ( rs = 0.292, p = 0.034; rs = 0.407, p = 0.003; and rs = 0.296, p = 0.031, respectively). Also, FOXP3% of positive Tregs was significantly correlated with LN class ( rs = 0.31, p = 0.024). Conclusion C4d-PTC, CD163-positive M2c macrophages and FOXP3-positive Tregs are markers that significantly correlated with chronicity in LN. Further studies are needed to evaluate their prognostic value.