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

• Published in: Clinical rheumatology Vol. 38; no. 11; pp. 3061 - 3071
• Main Authors: Reyes-Pérez, Itzel Viridiana, Sánchez-Hernández, Pedro Ernesto, Muñoz-Valle, José Francisco, Martínez-Bonilla, Gloria Esther, García-Iglesias, Trinidad, González-Díaz, Verónica, García-Arellano, Samuel, Cerpa-Cruz, Sergio, Polanco-Cruz, Julissa, Ramírez-Dueñas, María Guadalupe
• Format: Journal Article
• Language: English
• Published: London Springer London 01.11.2019; Springer Nature B.V
• Subjects: Adolescent; Adult; Aged; Arthritis, Rheumatoid - blood; Autoantibodies; Autoantibodies - blood; Autoimmune diseases; Cytokines; Cytokines - blood; Enzyme-linked immunosorbent assay; Erythrocyte sedimentation rate; Female; Humans; Inflammation; Interleukin 15; Interleukin 21; Male; Medicine; Medicine & Public Health; Middle Aged; Original Article; Protein-arginine deiminase; Rheumatoid arthritis; Rheumatology; Serum levels; Severity of Illness Index; Synovial membrane; Young Adult; γ-Interferon; Autoantibodies; Cytokines; Anti-CCP; Anti-MCV; Rheumatoid arthritis
• ISSN: 0770-3198; 1434-9949; 1434-9949
• DOI: 10.1007/s10067-019-04681-4

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.