The landscape of serum autoantibodies in lupus nephritis

Background and aim: Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN) are prototypes of autoimmune diseases. Mechanisms determining the renal evolution in SLE patients and the identification of predictive biomarkers remain an open issue. Methods: We reviwed data on serum levels of potential factors involved in SLE pathogenesis (i.e., NETs and dsDNA degradation) and autoantibodies associated with renal pathology (anti-dsDNA, anti-Histone 2 A and 3, anti-C1q, anti-ENO1, anti-ANXA1, anti-SOD2 IgG2) in patients recruited within the Italian collaborative Zeus study at the onset of renal symptoms (T0) and after 12 months (T12). Results: Clustering analysis based on a few serum parameters allowed the stratification of LN/SLE/controls into well-separated groups. High dsDNA degradation and high anti-ENO1 antibody levels contributed to stratifying SLE and LN, respectively. Anti-ENO1, anti-SOD2, and anti-H2 A/-H3 antibodies paralleled proteinuria levels during the follow up (high at T0 and normalized after 12 months), whereas anti-dsDNA and anti-C1q IgG2 remained high for the whole observation period. Hazard Risk regression analysis indicated that anti-ENO1 and anti-H2 A IgG2 were associated with proteinuria (>1 g) and renal failure (eGFR <60 mL/min) (HRs and 95% CI highly significant). Conclusions: Anti-ENO1 and anti-Histones 2A serum levels identify LN patients at the onset of renal symptoms and decrease following response to therapies. Both antibodies are associated with proteinuria and renal function loss. Our data support their use as predictive biomarkers for LN follow-up.