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

Rohit Aggarwal, Chester V. Oddis, Danielle Goudeau, Diane Koontz, Zengbiao Qi, Ann M. Reed, Dana P. Ascherman, Marc C. Levesque

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Objectives. To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 α (TIF1-α), -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-α (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-α 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-α 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.

Original languageEnglish (US)
Article numberkev444
Pages (from-to)991-999
Number of pages9
JournalRheumatology (United Kingdom)
Volume55
Issue number6
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Fingerprint

Myositis
Autoantibodies
Signal Recognition Particle
B-Lymphocytes
Muscles
ametantrone
Enzymes
Physicians
Serum
Rituximab
Linear Models
Transcription Factors
Biomarkers
Enzyme-Linked Immunosorbent Assay
Pediatrics
transcriptional intermediary factor 1

Keywords

  • Anti-Jo-1
  • Anti-SRP
  • Anti-TIF1-α and anti-Mi-2 autoantibodies
  • Autoantibody levels
  • Disease activity
  • Myositis
  • Rituximab

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Aggarwal, R., Oddis, C. V., Goudeau, D., Koontz, D., Qi, Z., Reed, A. M., ... Levesque, M. C. (2016). Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. Rheumatology (United Kingdom), 55(6), 991-999. [kev444]. https://doi.org/10.1093/rheumatology/kev444

Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. / Aggarwal, Rohit; Oddis, Chester V.; Goudeau, Danielle; Koontz, Diane; Qi, Zengbiao; Reed, Ann M.; Ascherman, Dana P.; Levesque, Marc C.

In: Rheumatology (United Kingdom), Vol. 55, No. 6, kev444, 01.06.2016, p. 991-999.

Research output: Contribution to journalArticle

Aggarwal, R, Oddis, CV, Goudeau, D, Koontz, D, Qi, Z, Reed, AM, Ascherman, DP & Levesque, MC 2016, 'Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab', Rheumatology (United Kingdom), vol. 55, no. 6, kev444, pp. 991-999. https://doi.org/10.1093/rheumatology/kev444
Aggarwal, Rohit ; Oddis, Chester V. ; Goudeau, Danielle ; Koontz, Diane ; Qi, Zengbiao ; Reed, Ann M. ; Ascherman, Dana P. ; Levesque, Marc C. / Autoantibody levels in myositis patients correlate with clinical response during B cell depletion with rituximab. In: Rheumatology (United Kingdom). 2016 ; Vol. 55, No. 6. pp. 991-999.
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abstract = "Objectives. To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 α (TIF1-α), -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-α (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-α 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-α 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.",
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AU - Qi, Zengbiao

AU - Reed, Ann M.

AU - Ascherman, Dana P.

AU - Levesque, Marc C.

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N2 - Objectives. To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 α (TIF1-α), -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-α (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-α 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-α 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.

AB - Objectives. To determine the longitudinal trends in serum levels of four myositis-associated autoantibodies: anti-Jo-1, -transcription intermediary factor 1 α (TIF1-α), -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-α (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-α 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-α 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.

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KW - Anti-SRP

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KW - Autoantibody levels

KW - Disease activity

KW - Myositis

KW - Rituximab

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