Serum extracellular matrix biomarkers in rheumatoid arthritis, psoriatic arthritis and psoriasis and their association with hand function

Introduction

Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PsO) are chronic inflammatory disorders that primarily affect the musculoskeletal system and the skin. RA is characterized by joint inflammation and cartilage degradation, leading to pain, swelling, and stiffness¹. PsO is a chronic auto-immune skin disease with erythematous and scaly patches in the skin, resulting from abnormal proliferation and differentiation of epidermal keratinocytes. Because up to 30% of patients with PsO progress to PsA (characterized by inflammatory arthritis, enthesitis, dactylitis and spondylitis²) PsO patients are considered an at-risk population to develop PsA. RA, PsA and PsO share several clinical features and have altered tissue turnover of the joints and skin, respectively^3,4. To avoid structural damage of the musculoskeletal system, timely treatment at disease onset or change of treatment with flare is the goal, and sensitive, pragmatic biomarkers for the detection of disease onset or flare are needed.

The extracellular matrix (ECM) consists of proteins, including collagen and proteoglycans, which provide support and elasticity to various tissues of joints and skin⁵. Type I and III collagens are the most abundant proteins in soft tissues, providing structural support, while type II collagen and aggrecan are key proteins in articular cartilage, maintaining tissue integrity^5,6. Type IV collagen forms the basement membrane, acting as a barrier between tissue compartments^5,7, and Type VI collagen contributes to tissue organization and stability of connective tissues such as the skin, tendons, and cartilage⁵. Vimentin is an intermediate filament protein involved in maintaining cellular structure and supporting tissue integrity⁸. Citrullinated vimentin has been predominantly studied as an autoantigen in RA and is elevated compared to controls⁹. However, there is emerging evidence of its potential role in PsA and PsO, suggesting its involvement in the inflammatory and tissue remodeling processes associated with these diseases¹⁰.

An altered ECM turnover leads to tissue inflammation, destruction, and fibrosis. The persistent strain leads to higher recruitment of immune cells which increase the concentration of degradative enzymes, such as metalloproteinases (MMP) and aggrecanases, resulting in a vicious cycle of tissue remodeling of the surrounding ECM in the various tissues¹¹. Several MMPs play a role in tissue degradation: MMP-1 degrades...