Abnormalities in soluble CD147 / MMPs / TIMPs axis in Ankylosing Spondylitis patients with and without a history of Acute Anterior Uveitis / Anomalii ale axei CD147 solubil / MMPs / TIMPs la pacienții cu spondilită anchilozantă cu sau fără uveită acută anterioară

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Abstract

Ankylosing Spondylitis (AS) is the prototype of the axial form of spondyloarthritis. Despite extensive studies, complex mechanisms related to abnormal cellular and molecular processes in AS are not completely understood. Among proinflammatory mediators such as proinflammatory cytokines, NOS-2, chemokines, which lead to inflammation, matrix metalloproteinases (MMPs) play an important role in inflammatory processes that characterize AS. Therefore, we purposed to evaluate whether the disruption of extracellular MMPs inducer (EMMPRIN/CD147), MMPs and tissue inhibitors of MMPs (TIMPs) homeostasis play a role in the evolution of AS especially in patients with a history of Acute Anterior Uveitis (AAU). For this purpose sera from AS patients and from healthy donors (HDs) were assessed for soluble CD147 (sCD147), MMP-3 and TIMP-1 levels using enzyme-linked immunosorbent assay and for the activity of MMP-2 and -9 gelatinases by gelatin zymography. The experimental results showed that the levels of sCD147, MMP-3 and TIMP-1 were significantly increased in AS patients compared to HDs. sCD147 as well as the ratio MMP-2/sCD147 differentiated AS patients with a history of AAU from those without it. The ratios MMP-2/sCD147, MMP-3/sCD147 and MMP-3/TIMP-1 suggested an imbalance between MMPs and their regulators in AS patients. These results suggest that MMPs/sCD147 ratios could be potential biomarkers to strengthen the characterization of AS patients and to predict disease evolution. Positive or negative correlations between some of the experimental and/or clinical features of AS patients and the therapy also highlight the usefulness of the evaluation of these biomarkers to identify an individualized and efficient therapy.

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