AB1154 MATRIX METALLOPROTEINASES, PROMISING BLOOD BIOMARKERS FOR EARLY AND ACCURATE DIAGNOSIS OF SYSTEMIC SCLEROSIS-RELATED INTERSTITIAL LUNG DISEASE
Authors: V. Pulito-Cueto, B. Atienza-Mateo, J. G. Ocejo-Vinyals, V. M. Mora-Cuesta, D. Iturbe Fernández, J. Batista-Liz, M. Sebastián Mora-Gil, M. Renuncio-García, E. González López, J. M. Cifrián-Martínez, R. Blanco, R. López-Mejías
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic sclerosis (SSc) is a potentially serious and disabling connective tissue disease, especially in the case of the appearance of interstitial lung disease (ILD), driving its mortality [1]. The development of fibrosis in SSc is accompanied by a continuous and dysbalanced tissue remodeling process that is controlled by various proteolytic enzymes. The matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases that can degrade all major connective tissue matrices and are regulated by their tissue inhibitors (TIMPs) [2]. These proteins have previously been involved in the development of several autoimmune diseases (AD) and lung complications, including ILD [2-4]. However, it is unclear what MMPs and TIMPs may be involved in extracellular matrix degradation and remodeling in SSc-ILD<sup>+</sup>. <h3>Objectives:</h3> The present study aimed to investigate whether certain MMPs and TIMPs could be potential biomarkers reflecting the lung fibrotic process in SSc patients. <h3>Methods:</h3> Peripheral venous blood was collected from 39 SSc-ILD<sup>+</sup> patients and three comparative groups: 20 SSc-ILD<sup>-</sup> patients, 63 patients with other AD-ILD<sup>+,</sup> and 39 idiopathic pulmonary fibrosis (IPF) patients. All subjects were recruited from the Hospital Universitario Marqués de Valdecilla (Santander, Spain). Serum levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, TIMP-1, and TIMP-2 were measured by using a chemiluminescent enzyme immunoassay and analyzed in the Fujirebio Lumipulse G600 II instrument. <h3>Results:</h3> Firstly, SSc-ILD<sup>+</sup> patients displayed increased levels of MMP-2, MMP-7, MMP-3, MMP-10 and MMP-12 in relation to SSc-ILD<sup>-</sup> patients (p=0.0310, p=0.0003, p&lt;0.0001, p=0.0039, p=0.0011; respectively, <b>Figure 1A, 1D-G</b>). Secondly, higher serum levels of MMP-1, MMP-2 and MMP-3 were found in patients with SSc-ILD<sup>+</sup> compared to those with other AD-ILD<sup>+</sup> (p=0.0009, p=0.0334, p=0.0108; respectively, <b>Figure 1A-B, 1D</b>). Regarding MMP-3, patients with SSc-ILD<sup>+</sup> exhibited lower levels than those with other AD-ILD<sup>+</sup> (p=0.0005, <b>Figure 1C</b>). Thirdly, the MMP-7, MMP-10 and MMP-12 levels were decreased in patients with SSc-ILD<sup>+</sup> concerning those with IPF (p=0.0189, p=0.0071, p=0.0459; respectively, <b>Figure 1D, 1F, 1G</b>). With regard to MMP-1, patients with SSc-ILD<sup>+</sup> showed increased levels compared with IPF patients (p=0.0250, <b>Figure 1A</b>). Finally, no differences in TIMP-1 and TIMP-2 levels were found between SSc-ILD<sup>+</sup> patients and the comparative groups (<b>Figure 1H-I</b>). <h3>Conclusion:</h3> Our study suggests that MMPs play a pathophysiological role in the remodeling of lung tissue in SSc-ILD<sup>+</sup>, and provides promising blood biomarkers for the early and accurate diagnosis of the disease. <h3>REFERENCES:</h3> [1] Am J Respir Crit Care Med.2020;201(6):650-660. [2] Ann Rheum Dis. 2012;71(6):1064-72. [3] PLoS Med. 2008;5(4):e93. [4] Front Pharmacol. 2022:13:805708. <i>VP-C is supported by funds of NVAL23/02 from IDIVAL; JCB-L is a recipient of a PFIS program fellowship from the ISCIII, co-funded by the European Social Fund ('Investing in your future'), (FI22/00020); MSM-G is supported by funds of "Fondo de Investigaciones Sanitarias" from ISCIII (PI121/00042); and RL-M is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF ("Investing in your future") (CPII21/00004).</i> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Verónica Pulito-Cueto: None declared, Belén Atienza-Mateo: None declared, J. Gonzalo Ocejo-Vinyals: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Joao Batista-Liz: None declared, María Sebastián Mora-Gil: None declared, Mónica Renuncio-García: None declared, Elena González López: None declared, José M. Cifrián-Martínez: None declared, Ricardo Blanco Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD, Abbvie, Pfizer, Roche, Bristol-Myers, Lilly, Janssen, and MSD, Abbvie, MSD, and Roche, Raquel López-Mejías: None declared.