Neutrophilic Activity Biomarkers (Plasma Neutrophil Extracellular Traps and Calprotectin) in Established Patients with Rheumatoid Arthritis Receiving Biological or JAK Inhibitors: A Clinical and Ultrasonographic Study

• Published in: Rheumatology and therapy. 2024-06, Vol.11 (3), p.501-521
• Main Authors: Frade-Sosa, Beatriz, Ponce, Andrés, Ruiz-Ortiz, Estíbaliz, De Moner, Noemí, Gómara, María J., Azuaga, Ana Belén, Sarmiento-Monroy, Juan C., Morlà, Rosa, Ruiz-Esquide, Virginia, Macías, Laura, Sapena, Nuria, Tobalina, Lola, Ramirez, Julio, Cañete, Juan D., Yague, Jordi, Auge, Josep M., Gomez-Puerta, José A., Viñas, Odette, Haro, Isabel, Sanmarti, Raimon
• Format: Article
• Language: English
• Subjects: Autoimmunity; Biomarkers; Calprotectin; Family Medicine; General Practice; Internal Medicine; Joint ultrasound; Kinases; Medicine; Medicine & Public Health; NETs; Neutrophils; Original Research; Orthopedics; Plasma; Quality of Life Research; Rheumatoid arthritis; Rheumatology; Ultrasonic imaging
• ISSN: 2198-6576; 2198-6584
• DOI: 10.1007/s40744-024-00650-9

Introduction This study assesses the accuracy of neutrophil activation markers, including neutrophil extracellular traps (NETs) and calprotectin, as biomarkers of disease activity in patients with established rheumatoid arthritis (RA). We also analyse the relationship between NETs and various types of therapies as well as their association with autoimmunity. Methods Observational cross-sectional study of patients with RA receiving treatment with biological disease-modifying antirheumatic drugs or Janus kinase inhibitors (JAK-inhibitors) for at least 3 months. Plasma calprotectin levels were measured using an enzyme-linked immunosorbent assay test kit and NETs by measuring their remnants in plasma (neutrophil elastase-DNA and histone-DNA complexes). We also assessed clinical disease activity, joint ultrasound findings and autoantibody status [reumatoid factor (RF), anti-citrullinated peptide/protein antibodies (ACPAs) and anti-carbamylated protein (anti-CarP)]. Associations between neutrophilic biomarkers and clinical or ultrasound scores were sought using correlation analysis. The discriminatory capacity of both neutrophilic biomarkers to detect ultrasound synovitis was analysed through receiver-operating characteristic (ROC) curves. Results One hundred fourteen patients were included. Two control groups were included to compare NET levels. The active control group consisted of 15 patients. The second control group consisted of 30 healthy subjects. Plasma NET levels did not correlate with clinical disease status, regardless of the clinic index analysed or the biological therapy administered. No significant correlation was observed between NET remnants and ultrasound synovitis. There was no correlation between plasma NET and autoantibodies. In contrast, plasma calprotectin positively correlated with clinical parameters (swollen joint count [SJC] rho = 0.49; P