Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and Response to Tumor Necrosis Factor (TNF) Inhibitors

Abstract

The term spondyloarthritis (SpA) is used to describe a group of multifactorial chronic inflammatory diseases characterized by a predisposing genetic background and clinical manifestations typically involving the sacroiliac joint. The absence of pathognomonic clinical and/or laboratory findings generally results in a delay in diagnosis and, consequently, in treatment. In addition, 20–40% of SpA patients are non-responders to tumor necrosis factor (TNF) inhibitor therapies. Given these considerations, it is important to identify biomarkers that can facilitate the diagnosis and assessment of disease activity. As inflammation plays a key role in the pathogenesis of SpA, inflammatory mediators have been investigated as potential biomarkers for diagnosing the disease and predicting response to therapy. Some investigators have focused their attention on the role of matrix metalloproteinases (MMPs), which are known to be markers of synovial inflammation that is generated in the joint in reaction to inflammatory stimuli. Several studies have been carried out to verify if serum MMPs levels could be useful to diagnose SpA, to assess disease severity, and to predict response to TNF inhibitor therapy. The current review focuses on MMPs’ role in SpA pathogenesis, diagnosis and therapeutic implications.

An update on serum biomarkers to assess axial spondyloarthritis and to guide treatment decision

“…142 Similar findings have been also found in PsA, further confirming the potential role of this molecule as a biomarker. 57–59 TNFi induce a significant and rapid decrease in serum MMP-3 levels together with a reduction in conventional variables (ESR and BASDAI). 61–63 A similar effect was observed after treatment with ustekinumab, although MMP-3 decrease was not associated with clinical variables.…”

Role of Semaphorins in Immunopathologies and Rheumatic Diseases

“…Spondyloarthritis is a polygenic rheumatic disease characterized by inflammation of the spine and peripheral joints, as well as extra-articular manifestations, such as inflammation in the intestinal tract, eyes, and skin. Spondyloarthritis comprises differently related but phenotypically distinct disorders, such as psoriatic arthritisarthritis related to inflammatory bowel disease; reactive arthritis, a subgroup of juvenile idiopathic arthritis; and ankylosing spondylitis, which is the prototypic and best-studied subtype [2,75,76,77]. RA and SpA are clinically distinct diseases with different etiologies, both are characterized by synovial hyperplasia, elevated synovial expression of many proinflammatory cytokines including TNFα, IL-1β, and IL-6, increased angiogenesis, and eventual joint destruction [24,76,78,79].…”

Novel approaches to develop biomarkers predicting treatment responses to TNF-blockers

“…In the Turina et al study [83], MMP3 showed a statistically significant decrease after two weeks of anti-TNF treatment, however, the effects of treatment were modest and less consistent across different subtypes of SpA. The impact of TNF inhibition on MMP3 levels is so far inconclusive with opposing results from different studies [184], raising the question of whether MMP3 can be used as a predictive biomarker for anti-TNF response. Some studies found a good predictive value for either baseline serum levels and/or reduction over time of MMP3 in SpA and PsA patients under anti-TNF [185,186],…”