Serum anti-signal recognition particle (SRP) autoantibody concentrations predict myositis patient response to Rituximab treatment


Contribution of Immunologic Factors

Poster Number: 73


Jennifer Peterson, PhD, Mei-Hsiu Chen, Kanneboyina Nagaraju, DVM, PhD, Chester Oddis, Rohit Aggarwal


1. The University of Toledo, 2. Binghamton University, 3. Binghamton University, 4. University of Pittsburgh Medical Center, 5. University of Pittsburgh Medical Center

Background: Idiopathic inflammatory myopathies (myositis) constitute a heterogenous group of rare disorders targeting muscle and/or skin. Rituximab (RTX) is a monoclonal antibody against CD20, a cell surface receptor primarily expressed on B cells. A randomized double-blind clinical trial was performed in 200 adult and pediatric refractory myositis patients. Despite no significant differences in the treatment arms for the primary and secondary end points, 83% of patients met primary response criteria. Autoantibodies are detectable in many patients, however treatment responses based on serum autoantibody concentrations have not been explored.

Objective: Determine if baseline serum concentrations of the most common autoantibodies found in myositis patients can predict whether patients will respond favorably to RTX treatment.

Approach: Serum concentrations of anti-Jo-1, anti-SRP, and transcription intermediary factor1-gamma (TIF1-g) were assessed prior to RTX treatment using validated ELISAs. Mann-Whitney tests were used to compare autoantibody levels for RTX responders and non-responders. Receiver Operating Characteristics (ROC) curves were constructed for each autoantibody, and the areas under the ROC curve (AUC) were used to assess the overall accuracy in predicting patient responder status.

Results: Anti-SRP serum concentrations were significantly (P-value < 0.05) higher among responders compared to non-responders and displayed high accuracy in discriminating responders to RTX therapy from non-responders (AUC = 0.90). Other pre-treatment autoantibodies were not significant in predicting responder status (anti-Jo-1 AUC = 0.61; anti-TIF1-g AUC = 0.44).

Conclusions: Anti-SRP autoantibodies are associated with severe, treatment refractory, necrotizing myositis, and these patients experience a poor prognosis. Our data show that patients with higher serum anti-SRP concentrations are more likely to respond to RTX therapy. These data may assist physicians in determining which patients will benefit from RTX therapy.