Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab

Consuelo M López de Padilla, Cynthia S. Crowson, Molly S. Hein, Michael A. Strausbauch, Rohit Aggarwal, Marc C. Levesque, Dana Ascherman, Chester V. Oddis, Ann M. Reed

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. Methods: In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Results: Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. Conclusion: IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

Original languageEnglish (US)
Pages (from-to)655-663
Number of pages9
JournalClinical and Experimental Rheumatology
Volume33
Issue number5
StatePublished - 2015

Fingerprint

Myositis
Chemokines
Interferons
Cytokines
Serum
Physicians
Muscles
Interleukin-13
Rituximab
Interleukin-8
Interleukin-1
Immunoassay
Interleukin-10
Interleukin-2
Interleukin-6
Placebos
Pediatrics
Lung
Skin
Therapeutics

Keywords

  • Core set measures
  • Refractory inflammatory myopathies
  • Rituximab
  • Serum cytokine scores
  • Toll-like receptors

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

de Padilla, C. M. L., Crowson, C. S., Hein, M. S., Strausbauch, M. A., Aggarwal, R., Levesque, M. C., ... Reed, A. M. (2015). Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab. Clinical and Experimental Rheumatology, 33(5), 655-663.

Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab. / de Padilla, Consuelo M López; Crowson, Cynthia S.; Hein, Molly S.; Strausbauch, Michael A.; Aggarwal, Rohit; Levesque, Marc C.; Ascherman, Dana; Oddis, Chester V.; Reed, Ann M.

In: Clinical and Experimental Rheumatology, Vol. 33, No. 5, 2015, p. 655-663.

Research output: Contribution to journalArticle

de Padilla, CML, Crowson, CS, Hein, MS, Strausbauch, MA, Aggarwal, R, Levesque, MC, Ascherman, D, Oddis, CV & Reed, AM 2015, 'Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab', Clinical and Experimental Rheumatology, vol. 33, no. 5, pp. 655-663.
de Padilla, Consuelo M López ; Crowson, Cynthia S. ; Hein, Molly S. ; Strausbauch, Michael A. ; Aggarwal, Rohit ; Levesque, Marc C. ; Ascherman, Dana ; Oddis, Chester V. ; Reed, Ann M. / Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab. In: Clinical and Experimental Rheumatology. 2015 ; Vol. 33, No. 5. pp. 655-663.
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abstract = "Objective: The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. Methods: In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Results: Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. Conclusion: IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.",
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T1 - Interferon-regulated chemokine score associated with improvement in disease activity in refractory myositis patients treated with rituximab

AU - de Padilla, Consuelo M López

AU - Crowson, Cynthia S.

AU - Hein, Molly S.

AU - Strausbauch, Michael A.

AU - Aggarwal, Rohit

AU - Levesque, Marc C.

AU - Ascherman, Dana

AU - Oddis, Chester V.

AU - Reed, Ann M.

PY - 2015

Y1 - 2015

N2 - Objective: The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. Methods: In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Results: Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. Conclusion: IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

AB - Objective: The purpose of this study was to investigate whether serum interferon (IFN)-regulated chemokine and distinct cytokine response profiles are associated with clinical improvement in patients with refractory inflammatory myopathy treated with rituximab. Methods: In a randomised, placebo-phase trial Rituximab in Myositis Trial (RIM), 200 refractory adult and paediatric myositis subjects received rituximab. Following rituximab, clinical response and disease activity were assessed. Serum samples and clinical data were collected at baseline and several time-points after rituximab treatment. Multiplexed sandwich immunoassays quantified serum levels of IFN-regulated chemokines and other pro-inflammatory cytokines. Composite IFN-regulated chemokine and Th1, Th2, Th17 and regulatory cytokine scores were computed. Results: Baseline IFN-regulated chemokine, Th1, Th2, Th17 and regulatory cytokine scores correlated with baseline physician global VAS, whereas the baseline Th1, Th2 and Th17 cytokine scores correlated with baseline muscle VAS. We also found baseline IFN-regulated chemokine scores correlated with specific non-muscular targets such as baseline cutaneous (r=0.29; p=0.002) and pulmonary (r=0.18; p=0.02) VAS scores. Among all cytokine/chemokines examined, the baseline score of IFN-regulated chemokines demonstrated the best correlation with changes in muscle VAS at 8 (r=-0.19; p=0.01) and 16 weeks (r=-0.17; p=0.03) following rituximab and physician global VAS at 16 weeks (r=-0.16; p=0.04). In vitro experiments showed increased levels of IL-8 (p=0.04), MCP-1 (p=0.04), IL-6 (p=0.03), IL-1β (p=0.04), IL-13 (p=0.04), IL-10 (p=0.02), IL-2 (p=0.04) and IFN-γ (p=0.02) in supernatants of TLR-3 stimulated PBMCs from non-responder compared to patients responders to rituximab. Conclusion: IFN-regulated chemokines before treatment is associated with improvement in disease activity measures in refractory myositis patients treated with rituximab.

KW - Core set measures

KW - Refractory inflammatory myopathies

KW - Rituximab

KW - Serum cytokine scores

KW - Toll-like receptors

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