Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab

Abstract

Objectives: To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 γ (TIF1-γ), -signal recognition particle (SRP) and -Mi-2, after B cell depletion with rituximab, and to determine the longitudinal association of these autoantibody levels with disease activity as measured by myositis core-set measures (CSMs).

Methods: Treatment-resistant adult and pediatric myositis subjects (n = 200) received rituximab in the 44-week Rituximab in Myositis Trial. CSMs [muscle enzymes, manual muscle testing (MMT), physician and patient global disease activity, HAQ, and extramuscular disease activity] were evaluated monthly and anti-Jo-1 (n = 28), -TIF1-γ (n = 23), -SRP (n = 25) and -Mi-2 (n = 26) serum levels were measured using validated quantitative ELISAs. Temporal trends and the longitudinal relationship between myositis-associated autoantibodies levels and CSM were estimated using linear mixed models.

Results: Following rituximab, anti-Jo-1 levels decreased over time (P < 0.001) and strongly correlated with all CSMs (P < 0.008). Anti-TIF1-γ levels also decreased over time (P < 0.001) and were only associated with HAQ, MMT and physician and patient global disease activity. Anti-SRP levels did not change significantly over time, but were significantly associated with serum muscle enzymes. Anti-Mi-2 levels significantly decreased over time and were associated with muscle enzymes, MMT and the physician global score.

Conclusion: Anti-Jo-1, anti-TIF1-γ and anti-Mi-2 levels in myositis subjects decreased after B cell depletion and were correlated with changes in disease activity, whereas anti-SRP levels were only associated with longitudinal muscle enzyme levels. The strong association of anti-Jo-1 levels with clinical outcomes suggests that anti-Jo-1 autoantibodies may be a good biomarker for disease activity.

Keywords: and anti-Mi-2 autoantibodies; anti-Jo-1; anti-SRP; anti-TIF1-γ; autoantibody levels; disease activity; myositis; rituximab.

Fig. 1

Normalized levels of six core set measures and autoantibody levels for patients with anti-Jo-1, anti-SRP, anti-TIF1-γ and anti-Mi-2 autoantibodies Each measure was transformed to approximately normal distribution using Box–Cox transformation, and standardized to have a mean of 0 and variance of 1.

Fig. 2

Relative percentage change from baseline (pre-rituximab) to follow-up (post-rituximab) of anti-Jo-1, anti-SRP, anti-TIF1-γ and anti-Mi2 autoantibody levels (A) anti-Jo-1. (B) anti-SRP. (C) anti-TIF1-γ. (D) anti-Mi2. Median levels are connected with a straight line; dots indicate mean levels.