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

Background:: Tubulointerstitial inflammation (TII) in lupus nephritis (LN) is associated with a worse prognosis. Vimentin, a filamental antigen, is commonly targeted by activated B-cells in TII. The prognostic importance of high serum anti-vimentin antibodies (AVAs) in LN 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 Inititative 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 (RA) associated antibodies, and hierarchically clustered. Serum from baseline, 26 and 52 weeks from 132 LUNAR trial enrolled LN 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 RA associated antibodies. In LUNAR at baseline, AVAs correlated weakly with anti-dsDNA and more strongly with anti-cardiolipin titres. Regardless of treatment, IgG-, but not IgM- or IgA-, AVAs were higher at week 52 than at baseline. In contrast, anti-dsDNA titres declined, regardless of therapeutic regime. High IgG AVA titres at entry predicted less response to therapy.

Conclusion:: AVAs, especially IgG AVAs, are unique in distribution and response to therapy compared to other commonly measured autoantibody specificities. Furthermore, high-titre IgG AVAs identify LN patients resistant to conventional therapies. These data suggest that AVAs represent an independent class of prognostic autoantibodies.