Anti-vimentin antibodies: a unique antibody class associated with therapy-resistant lupus nephritis

Abstract

Background Tubulointerstitial inflammation (TII) in lupus nephritis is associated with a worse prognosis. Vimentin, a filamental antigen, is commonly targeted by in situ activated B-cells in TII. The prognostic importance of high serum anti-vimentin antibodies (AVAs) in lupus nephritis and their relationship with common lupus autoantibody specificities is unknown. Herein we investigated associations between AVA isotypes, other autoantibodies, and response to mycophenolate mofetil (MMF) in the presence or absence of rituximab. Methods The Translational Research Initiative in the Department of Medicine (TRIDOM) cross-sectional cohort of 99 lupus patients was assayed for IgG-, IgA- and IgM- AVAs, lupus-associated and rheumatoid arthritis-associated antibodies, and hierarchically clustered. Serum from baseline, 26 and 52 weeks from 132 Lupus Nephritis Assessment with Rituximab (LUNAR) trial enrolled lupus nephritis patients was also analysed and correlated with renal function up to week 78. Results In TRIDOM, AVAs, especially IgM AVAs, clustered with IgG anti-dsDNA and away from anti-Sm and -RNP and rheumatoid arthritis-associated antibodies. In LUNAR at baseline, AVAs correlated weakly with anti-dsDNA and more strongly with anticardiolipin titers. Regardless of treatment, IgG-, but not IgM- or IgA-, AVAs were higher at week 52 than at baseline. In contrast, anti-dsDNA titers declined, regardless of therapeutic regime. High IgG AVA titers at entry predicted less response to therapy. Conclusion AVAs, especially IgG AVAs, are unique in distribution and response to therapy compared with other commonly measured autoantibody specificities. Furthermore, high-titer IgG AVAs identify lupus nephritis patients resistant to conventional therapies. These data suggest that AVAs represent an independent class of prognostic autoantibodies.