Aberrant expression of C1q, IL-6 and β-catenin in class VI lupus nephritis

Abstract

Background: complement component C1q, interleukin-6 (IL-6) and β-catenin have been implicated in the pathogenesis of lupus nephritis (LN). However, their correlation with the pathological progression and type of LN remain unclear. Methods: the concentrations of C1q, IL-6 and β-catenin were evaluated in plasma, urine and kidney tissues in LN patients, non-LN systemic lupus erythematosus (SLEn) patients, and healthy cohorts, as well as C57BL/6, IL-6-/-, MRL-Fas/lpr and MRL-Fas/lprIL-6-/- mice. Results: more abundant plasma C1q, IL-6 and urine C1q proteins were determined in LN and SLEn patients compared to healthy cohorts. Of note, the concentration of IL-6 and β-catenin in both plasma and urine, and plasma C1q was even higher in LN patients relative to SLEn subjects. Moreover, positive correlations were determined for C1q and β-catenin proteins between plasma and urine in LN patients. Of importance, both plasma and urine β-catenin, and urine IL-6 were significantly increased in patients with class VI LN patients relative to those who suffered from class I LN. Immunohistochemical study further uncovered that the abundant IL-6 and β-catenin proteins were deposited in both renal glomeruli and tubules, while the C1q was only found in renal glomeruli of patients with class IV LN. Consistent with the clinical findings, experimental studies in MRL-Fas/lprIL-6-/- mice also showed a decreased β-catenin in urine, C1q and β-catenin in kidney tissues of MRL-Fas/lprIL-6-/- mice compared with MRL-Fas/lpr mice. Interestingly, mice with deficiency of IL-6 exhibited less degrees of proteinuria and histological lesions, and reduced serum anti-double-stranded DNA (anti-dsDNA) antibody and sizes of spleen and inguinal node, as compared with MRL-Fas/lpr and C57/BL6 control mice. Conclusions: these data suggest a strong correlation among IL-6, C1q and β-catenin in the pathogenesis of type VI LN in SLE patients, indicating that they may be valuable biomarkers for nephrologists to guide treatment and predict prognosis among these patients.