title: Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh Department of Medicine, Pittsburgh, PA, docrota@gmail.com.
authors.forename: Rohit
authors.initials: R
authors.lastname: Aggarwal
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh Department of Medicine, Pittsburgh, PA.
authors.forename: Chester V
authors.initials: CV
authors.lastname: Oddis
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh Department of Medicine, Pittsburgh, PA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Goudeau
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh Department of Medicine, Pittsburgh, PA.
authors.forename: Diane
authors.initials: D
authors.lastname: Koontz
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh Department of Medicine, Pittsburgh, PA.
authors.forename: Zengbiao
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, NC and.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
authors.affiliation: Division of Rheumatology and Immunology, University of Miami Department of Medicine, Miami, FL, USA.
authors.forename: Dana P
authors.initials: DP
authors.lastname: Ascherman
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Pittsburgh Department of Medicine, Pittsburgh, PA.
authors.forename: Marc C
authors.initials: MC
authors.lastname: Levesque
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D002648:Child; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000097:blood; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology; D009220:Myositis / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D000069283:Rituximab / Q000627:therapeutic use*; D012720:Severity of Illness Index; D018271:Signal Recognition Particle / Q000097:blood; D014157:Transcription Factors / Q000097:blood; D016896:Treatment Outcome
chemical_list: D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; C115323:CHD4 protein, human; C046750:Jo-1 antibody; D018271:Signal Recognition Particle; C511956:TRIM33 protein, human; D014157:Transcription Factors; D000069283:Rituximab; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
keywords: and anti-Mi-2 autoantibodies; anti-Jo-1; anti-SRP; anti-TIF1-γ; autoantibody levels; disease activity; myositis; rituximab