The Association Between Systemic Inflammation as Measured by Calprotectin and Autoantibody Load in Rheumatoid Arthritis

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Objective: Plasma calprotectin is a marker of neutrophil activity. Its relation to the clinical phenotype and autoantibodies in rheumatoid arthritis (RA) is only partly understood. We therefore aimed to investigate the association between calprotectin and the clinical parameters C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti–cyclic citrullinated peptide 2 (anti‐CCP2), and other anti–modified protein antibodies (AMPAs) in patients with RA. Methods: Rheumatoid factor (RF), anti‐CCP2 isotypes, and plasma calprotectin were centrally measured in a cross‐sectional cohort of 4,521 Scandinavian patients with RA using fluoro‐enzyme immunoassays. IgG to 15 citrullinated (Cit) and 4 carbamylated or acetylated (Carb/Acet) peptides were measured by multiplex solid‐phase array. CRP and ESR values were obtained from clinical measurements at the time of blood sampling. Results: Calprotectin levels correlated with ESR (ρ = 0.53), CRP (ρ = 0.47), visual analog scale (VAS) pain (ρ = 0.24), Swollen Joint Count in 28 joints (SJC28; ρ = 0.39), and Tender Joint Count in 28 joints (TJC28; ρ = 0.26; P < 0.0001 for all). Patients with both elevated CRP (>10 mg/L) and calprotectin (>15 arbitrary units/mL) (14%, n = 613) had significantly higher VAS pain, SJC28, and TJC28 scores than patients with only elevated CRP ( P < 0.0001), in early and established disease. Patients with elevated calprotectin, independent of CRP levels, had significantly higher proportions of AMPA positivity, including anti‐CCP2. When patients were divided into six groups based on increasing number of Cit/Carb/Acet reactivities and anti‐CCP2 IgG levels, elevated calprotectin was associated with increasing AMPA load, particularly in the presence of RF IgM. The differences between AMPA load groups remained after adjusting for sex, age, RF IgM, and disease duration. Conclusion: Plasma calprotectin is positively associated with seropositivity and AMPA load by autoantibody levels and the breadth of the autoantibody response.
Funding Information
  • Reumatikerförbundet (R‐1012541)
  • Reumatikerförbundet (R‐1033940)
  • Stiftelsen Konung Gustaf V:s 80-årsfond (FAI‐2023‐0956)
  • Stiftelsen Konung Gustaf V:s 80-årsfond (FAI‐2025‐1172)
  • NordForsk (90825‐Project_NORA)
  • Hjärt-Lungfonden (20250711)
  • VINNOVA (2024‐01145)
  • Vetenskapsrådet (2023‐01827)
  • Vetenskapsrådet (2023‐02497)

This publication has 35 references indexed in Scilit: