A recent study published in Arthritis Research and Therapy has revealed promising findings in the search for predictive biomarkers of treatment response in polyarticular juvenile idiopathic arthritis (pJIA). The research, focusing on the effectiveness of abatacept, identified S100A8/9 and S100A12 proteins as potential indicators of treatment success.
The study, part of a phase 3 trial, involved 219 patients with active pJIA treated with subcutaneous abatacept. Key findings revealed that lower baseline levels of S100A8/9 (≤ 3295 ng/mL) were associated with higher odds of achieving various clinical endpoints. Notably, patients with lower S100A8/9 levels had an increased likelihood of achieving JIA- American College of Rheumatology (ACR) 90, JIA-ACR100, and JIA-ACR inactive disease in month 4. This trend persisted in month 16, with lower baseline S100A8/9 levels correlating with higher odds of achieving JIA-ACR inactive disease (ID). Similarly, lower baseline S100A12 levels (≤ 176 ng/mL) were associated with improved outcomes. Patients with lower S100A12 levels had greater odds of achieving JIA-ACR90, JIA-ACR100, and JIA-ACR ID in month 4. These associations remained significant in month 16. The study also observed that from baseline to month 4, decreases in S100A8/9 and S100A12 levels generally exceeded 50% among JIA-ACR90/100/ID responders. This finding suggests that monitoring changes in these biomarker levels during treatment could potentially predict longer-term response to abatacept in pJIA.
Abatacept, a selective modulator of CD80/86 co-stimulation that inhibits T-cell activation and disrupts antigen presentation, has proven to be effective and well-tolerated for the treatment of pJIA when administered either intravenously or subcutaneously. S100 proteins, a family of small proteins unique to vertebrates, are widely expressed across various cell types and play crucial roles in regulating calcium homeostasis, glucose metabolism, cell proliferation, apoptosis, inflammation, and tumorigenesis. The S100 family includes more than 20 distinct EF-hand calcium (Ca2+)-binding proteins, such as S100A8, S100A9, and S100A12, which are commonly found in neutrophils, macrophages, monocytes, and other immune cells. These specific S100 proteins are implicated in the pathogenesis of immune-related disorders, contributing to the development of autoimmune diseases like psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.
S100A8/9 and S100A12 proteins may serve as early predictive biomarkers in pJIA, potentially guiding treatment decisions. Lower baseline levels of these proteins predicted better response to abatacept treatment, which could aid in identifying patients more likely to benefit from this therapy. For rheumatologists, these findings represent a significant step towards personalized medicine in pJIA treatment. The ability to predict treatment response based on biomarker levels could potentially optimize patient care, allowing for more informed decisions about treatment strategies and potentially improving outcomes for children with pJIA. However, as with all emerging research, further studies will be necessary to validate these findings and establish standardized protocols for biomarker-guided treatment decisions in clinical practice.
References
- Brunner HI, Schulert GS, Sproles A, Thornton S, Cornejo GV, Antón J et al. S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis. Arthritis Res Ther. 2024 Jun 25;26(1):125.
- Xia P, Ji X, Yan L, Lian S, Chen Z, Luo Y. Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity. Immunology. 2024 Mar;171(3):365-376.