Identification of early risk factors for anti-citrullinated-protein-antibody positive rheumatoid arthritis—a prospective cohort study
Rheumatology, 2024
Cîrciumaru A., Kisten Y., Hansson M., Mathsson-Alm L., Joshua V., Wähämaa H., Loberg Haarhaus M., Lindqvist J., Padyukov L., Catrina S., Fei G., Vivar N., Rezaei H., af Klint E., Antovic A., Réthi B., Catrina A., Hensvold A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Objective
Individuals positive for anti-cyclic-peptide-antibodies (anti-CCP) and musculoskeletal complaints (MSK-C) are at risk for developing rheumatoid arthritis (RA). In this study we aimed to investigate factors involved in arthritis progression.
Methods
Anti-CCP2-positive individuals with MSK-C referred to a rheumatologist were recruited. Individuals lacked arthritis at clinical and ultrasound examination and were followed for ≥3 years or until clinical arthritis diagnosis. Blood samples from inclusion were analysed for nine ACPA reactivities (citrullinated α-1-enolase, fibrinogen, filaggrin, histone, vimentin and tenascin peptides); 92 inflammation-associated proteins; and HLA-shared epitope alleles. Cox regression was applied to the data to identify independent predictors in a model.
Results
Two hundred and sixty-seven individuals were included with median follow-up of 49 months (interquartile range [IQR]: 22–60); 101 (38%) developed arthritis after a median of 14 months (IQR: 6–27). The analysis identified that presence of at least one ACPA reactivity (hazard ratio [HR] 8.0; 95% CI: 2.9, 22), ultrasound-detected tenosynovitis (HR 3.4; 95% CI: 2.0, 6.0), IL-6 levels (HR 1.5; 95% CI: 1.2, 1.8) and IL-15 receptor α (IL-15Rα) levels (HR 0.6; 95% CI: 0.4, 0.9) are significant independent predictors for arthritis progression in a prediction model (Harrell’s C 0.76 [s.e. 0.02], AUC 0.82 [95% CI: 0.76, 0.89], cross-validated AUC 0.70 [95% CI: 0.56, 0.85]).
Conclusion
We propose a high RA risk phase characterized by presence of ACPA reactivity, tenosynovitis, IL-6 and IL-15Rα and suggest that these factors need to be further investigated for their biological effects and clinical values, to identify individuals at particular low risk and high risk for arthritis progression.