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Clinical Rheumatology

, Volume 38, Issue 11, pp 3061–3071 | Cite as

Cytokines (IL-15, IL-21, and IFN-γ) in rheumatoid arthritis: association with positivity to autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) and clinical activity

  • Itzel Viridiana Reyes-Pérez
  • Pedro Ernesto Sánchez-HernándezEmail author
  • José Francisco Muñoz-Valle
  • Gloria Esther Martínez-Bonilla
  • Trinidad García-Iglesias
  • Verónica González-Díaz
  • Samuel García-Arellano
  • Sergio Cerpa-Cruz
  • Julissa Polanco-Cruz
  • María Guadalupe Ramírez-DueñasEmail author
Original Article
  • 126 Downloads

Abstract

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane damage and autoantibody production. RA is a heterogeneous disease, where cytokines such as IL-15, IL-21, and IFN-γ have been associated. However, their association with the autoantibodies has not been clearly described. The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity.

Methodology

This study included 153 RA patients and 80 control subjects (CS). The levels of IL-15, IL-21, IFN-γ, anti-CCP, anti-MCV, and anti-PADI4 were quantified by ELISA, whereas RF was quantified by turbidimetry. The disease activity was evaluated by the indices disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI), and simple disease activity index (SDAI).

Results

The serum levels of IL-15, IL-21, and IFN-γ, and autoantibodies were increased in RA patients, compared with CS (p < 0.05). A correlation was found between IL-21 and anti-CCP and anti-MCV (p < 0.05). According to RA evolution, RF, anti-CCP, and anti-MCV had higher levels in early RA. In addition, increased levels of IL-21 were observed in RA seropositive patients (RF/anti-CCP/anti-MCV). The higher levels of both cytokines and autoantibodies were observed in moderate activity, evaluated by the three indices.

Conclusions

Our results suggest that the increased soluble levels of IL-15, IL-21, and IFN-γ are involved in the inflammatory network in RA. However, IL-21 serum levels are associated with higher titers of autoantibodies (RF, anti-CCP, and anti-MCV) and IL-15 with moderate activity.

Key Points

• IL-15, IL-21, and IFN-y are associated with the immunopathology of RA, but not significantly with the evolution of the disease.

• RF, anti-CCP, and anti-MCV had higher levels in early than established RA.

• IL-21 has an association with RF, anti-CCP, and anti-MCVand, for this reason, could be proposed as a disease biomarker.

• Patients with activity moderate of disease showed higher levels of RF, anti-CCP, anti-MCV, and IL-15.

Keywords

Anti-CCP Anti-MCV Autoantibodies Cytokines Rheumatoid arthritis 

Notes

Acknowledgments

RPIV was a Ph.D. CONACYT fellow (Reg. 575070).

Funding

This research was performed with the financial support of the PRO-SNI 2016-2017 program from Universidad de Guadalajara granted to SHPE and RDMG.

Compliance with ethical standards

All individuals have written an informed consent letter, in agreement with the Code of Ethics of the World Medical Association (Declaration of Helsinki, Brazil 2013). The ethics, research, and biosafety committees of Hospital Civil de Guadalajara “Fray Antonio Alcalde” (Reg. No. 037/16) approved this study.

Disclosures

None.

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Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  • Itzel Viridiana Reyes-Pérez
    • 1
  • Pedro Ernesto Sánchez-Hernández
    • 1
    Email author
  • José Francisco Muñoz-Valle
    • 2
  • Gloria Esther Martínez-Bonilla
    • 3
  • Trinidad García-Iglesias
    • 1
  • Verónica González-Díaz
    • 3
  • Samuel García-Arellano
    • 2
  • Sergio Cerpa-Cruz
    • 3
  • Julissa Polanco-Cruz
    • 3
  • María Guadalupe Ramírez-Dueñas
    • 1
    Email author
  1. 1.Laboratorio de Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMexico
  2. 2.Instituto de Investigación en Ciencias Biomédicas, Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMexico
  3. 3.Servicio de Reumatología, Hospital Civil Fray Antonio AlcaldeGuadalajaraMexico

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