High levels of natural killer cells are associated with response to tocilizumab in patients with severe rheumatoid arthritis.

Authors:
Dr Claire Immediato Daïen, MD PhD
Dr Claire Immediato Daïen, MD PhD
IGMM CNRS UMR5535, Montpellier hospital
Dr
Rhuematology
Montpellier , France | France

Rheumatology (Oxford) 2015 Apr 16;54(4):601-8. Epub 2014 Sep 16.

Department of Rheumatology, Lapeyronie Hospital and Montpellier University I, TNF-alpha Laboratory, UMR5535, CNRS, Clinical Investigation Center, University Hospital of Montpellier and INSERM, CIC 1001, Montpellier, France, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université Montpellier Sud de France, France. Department of Rheumatology, Lapeyronie Hospital and Montpellier University I, TNF-alpha Laboratory, UMR5535, CNRS, Clinical Investigation Center, University Hospital of Montpellier and INSERM, CIC 1001, Montpellier, France, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands and Institut de Génétique Moléculaire de Montpellier, UMR5535, CNRS, Université Montpellier Sud de France, France.

Objectives: We aimed to assess the effect of tocilizumab (TCZ), an IL-6 receptor inhibitor, on B, T, NK and NKT cells in patients with RA and to study the cell type predictors of remission. We also compared NK cells in patients with RA and in controls.

Methods: RA patients included in the study met the 2010 ACR/European League Against Rheumatism (EULAR) criteria, were receiving stable doses of steroids and had not received rituximab in the previous year. Different B and T cell subsets, NK cells and NKT cells were assessed by flow cytometry along with perforin A and granzyme B to estimate NK cell cytotoxicity.

Results: We included 92 RA patients, including 20 requiring TCZ treatment and 15 requiring anti-TNF drugs, and 25 controls. At baseline, the proportion of CD56(dim)CD16(+)CD3(-) NK cells was inversely correlated with the 28-joint DAS (DAS28). In TCZ-treated patients, the baseline proportion of CD3(-)CD56(+) NK cells was inversely correlated with the change in DAS28 at 3 months and the proportion was 3-fold greater for patients with DAS28 remission at 3 months than other patients. Change in the proportion of CD56(bri)CD16(-) NK cells was linearly correlated with change in the DAS28 at 3 months. The baseline proportion of NK cells did not predict change in disease activity at 3 months with anti-TNF therapy. The perforin content in NK cells increased with TCZ treatment.

Conclusion: This study supports NK cell involvement in RA and in the TCZ mechanism of action. NK cells at baseline could be a predictive factor of TCZ response if results are confirmed.

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http://dx.doi.org/10.1093/rheumatology/keu363DOI Listing
April 2015
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