A prospective follow-up study found that psoriatic arthritis patients with higher synovial immunohistochemical reactivity of IL-17A, DKK1, and TGF-β1 are more likely to benefit from early initiation of biologics.
Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting joints and skin in patients with psoriasis. It exhibits progressive and destructive joint changes, with significant pathological alterations occurring early in the disease course, often leading to structural damage within 2 years of onset.
In a prospective follow-up of a previously published cross-sectional study, researchers tried to determine the cytokine profile of inflammation in PsA patients using synovial immunohistochemistry (IHC) to identify a group of patients who are most likely to benefit from early initiation of biologics. The study’s results are published in the journal Biomedicines.
Immunohistochemical Reactivity of Specific Cytokines Can Help Identify Patients for Early Biologics Initiation
The pathogenesis of PsA involves elevated levels of interleukins (ILs) such as IL-1β, IL-6, IL-17, IL-22, IL-23, interferon-γ, and tumor necrosis factor-α (TNF-α), which contribute to inflammation and joint damage. This study aimed to analyze early cytokine profiles in the synovial tissue (ST) of PsA patients, comparing them with those in RA, osteoarthritis (OA), and ankylosing spondylitis (AS) to explore their potential as biomarkers for disease progression and the need for biological treatment initiation.
The study included patients fulfilling the classification for psoriatic arthritis (CASPAR) criteria as well as RA, OA, and AS patients, who underwent knee arthroscopy due to persistent joint swelling and tenderness despite treatment. Synovial membrane samples were collected and analyzed for TGF-β1, IL-17A, Dickkopf-related protein (DKK)1, bone morphogenic protein (BMP)2, BMP4, and Wnt5b expression. Patients diagnosed with PsA or RA were initiated on methotrexate therapy, with some transitioning to TNF-α inhibitors or combination therapy based on treatment guidelines. Clinical and biological data were collected at baseline and at the final assessment.
Results showed that elevated TGF-β1 expression in PsA patients positively correlated with IL-17A and DKK1, particularly in those requiring biologic therapy. Higher levels of IL-17A, TGF-β1, and DKK1 were observed in PsA patients treated with biologics compared to those untreated or with other arthritic conditions.
Further analysis revealed that IL-17A, TGF-β1, and DKK1 levels in early synovial tissue were associated with worse disease outcomes, with higher expression in patients requiring biologic therapy. The combination of these cytokines showed high sensitivity and specificity in predicting the need for biologics.
IL-17A, a key pro-inflammatory cytokine in PsA pathogenesis, was found to be a potential biomarker for disease severity and treatment response. Elevated DKK1 levels in synovial tissue indicated joint damage and correlated with disease progression in PsA.
The Bottom Line
The study underscores the importance of early detection and personalized treatment approaches in PsA. Although current treatment decisions rely on various factors, including disease severity and previous therapy, identifying biomarkers like IL-17A, TGF-β1, and DKK1 could enhance precision medicine in PsA management.
Limitations of the study include its single-center design, small sample size, and invasive nature of synovial biopsy needed for carrying out IHC. Future research should focus on validating these biomarkers in larger studies to improve their clinical utility in PsA management.
Source:
Tasende, J. a. P., Fernández-Moreno, M., Rego‐Pérez, I., Fernandez-Lopez, J., Oreiro-Villar, N., De Toro Santos, F. J., & Blanco, F. J. (2024). Higher Synovial Immunohistochemistry Reactivity of IL-17A, Dkk1, and TGF-β1 in Patients with Early Psoriatic Arthritis and Rheumatoid Arthritis Could Predict the Use of Biologics. Biomedicines, 12(4), 815. https://doi.org/10.3390/biomedicines12040815
