You are here

  • Home
  • Archive
  • Volume 3, Issue 2
  • Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis

Article Text

Article menu

Download PDFPDF

Rheumatoid arthritis
Original article
Variants of genes implicated in type 1 interferon pathway and B-cell activation modulate the EULAR response to rituximab at 24 weeks in rheumatoid arthritis
  1. Pierre-Antoine Juge1,
  2. Steven Gazal2,
  3. Arnaud Constantin3,4,
  4. Xavier Mariette5,6,
  5. Bernard Combe7,
  6. Jacques Tebib8,
  7. Maxime Dougados9,10,
  8. Jean Sibilia11,
  9. Xavier Le Loet12 and
  10. Philippe Dieudé1,13
  1. 1Department of Rheumatology, Assistance Publique—Hôpitaux de Paris, Bichat Hospital, Université Paris Diderot, Paris, France
  2. 2Plateforme de Génomique Constitutionnelle, Assistance Publique—Hôpitaux de Paris, Bichat Hospital, Université Paris Diderot, Paris, France
  3. 3UMR 1027, INSERM, Toulouse III University, Toulouse, France
  4. 4Department of Rheumatology, Hôpital Purpan, CHU Toulouse, Toulouse, France
  5. 5Department of Rheumatology, Université Paris-Sud, Assistance Publique—Hôpitaux de Paris, Paris, France
  6. 6INSERM U1184, Université Paris-Sud, Paris, France
  7. 7Department of Rheumatology, Service d’Immuno-Rhumatologie, Montpellier, France
  8. 8Department of Rheumatology, Hôpital Lyon-sud, Pierre-Bénite, France
  9. 9Department of Rheumatology, Université Paris Descartes, Hôpital Cochin, Assistance Publique—Hôpitaux de Paris, Paris, France
  10. 10INSERM U1153, PRES Sorbonne Paris-Cité, Paris, France
  11. 11Centre de Référence des Maladies Auto-immune Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  12. 12Department of Rheumatology, Rouen University Hospital, Rouen, France
  13. 13INSERM U699, Université de Paris Diderot, PRES Sorbonne Paris-Cité, Paris, France
  1. Correspondence to Pr Philippe Dieudé; philippe.dieude{at}aphp.fr

Abstract

Background The type 1 interferon (IFN) pathway has been identified to potentially affect the response to rituximab (RTX) for rheumatoid arthritis (RA), which suggests the contribution of type 1 IFN pathway genes such as IFN regulatory factor 5 and 7 (IRF5 and IRF7), tyrosine kinase 2 (TYK2), signal transducer and activator of transcription 4 (STAT4) and osteopontin (SPP1). Our objective was to study functional variants of these IFN pathway genes as predictors of the European League Against Rheumatism (EULAR) response to RTX for RA at week 24 (W24).

Methods Logistic regression analysis with a stepwise multivariate model adjusted for sex, age and DAS28-CRP (Disease Activity Score in 28 joints with C reactive protein) in 115 patients from the SMART randomised studywas used to analyse the association between the candidate variants and W24 EULAR response. Because the variant TNFSF13B rs9514828 was previously found associated with RTX response in the same population, it was included in the analysis.

Results The combination of IRF5 rs2004640, SPP1 rs9138 and TNFSF13B rs9514828 was strongly associated with good/moderate EULAR response to RTX at W24: p=9.34×10−6, OR 11.37 (95% CI 4.03 to 35.28), positive predictive value 91% and negative predictive value 54%.

Conclusion Our results support the contribution of the IRF5, SPP1 and TNFSF13B genotypic combination in the response to RTX for RA at W24.

  • rheumatoid arthritis
  • gene polymorphism
  • pharmacogenetics

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/rmdopen-2017-000448

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors P-AJ and PD designed the study. All authors collected the patients’ data. SG and PD carried out the statistical analyses. P-AJ and PD wrote the first version of the manuscript. All authors read and approved the final version of the manuscript.

    • Funding SMART study was sponsored by ROCHE, France.

    • Competing interests PD is supported by an unrestricted grant from ROCHE.

    • Patient consent Obtained.

    • Ethics approval The main SMART study was approved by the local ethics committee (Groupe Hospitalier Pitié-Salpêtrière, Paris).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Data are available on demand by emailing the corresponding author.