AB1219 ASSOCIATION OF ADHESION MOLECULES WITH INTERSTITIAL LUNG DISEASE AND VASCULAR EVENTS IN TWO RARE DISEASES: IDIOPATHIC INFLAMMATORY MYOPATHY AND SYSTEMIC SCLEROSIS!
Authors: J. Colic, A. Notarnicola, M. Sefik Bukilica, I. E. Lundberg, A. Antovic
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Interstitial lung disease (ILD) is a common manifestation and the leading cause of death in two rare autoimmune connective tissue diseases, systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM). The pathophysiology of ILD is not fully understood. The risk of thrombotic events (TE) is high in both diseases. Recently, E selectin was found as a possible marker of TE in IIM cohort, while ICAM1 was associated with prothrombotic fibrin clots in patients with digital ulcers (DU) in SSc [1-3]. However, the relation of adhesion molecules with vascular events (VE) in patients with ILD related to SSc or IIM was not previously investigated. <h3>Objectives:</h3> To evaluate the serum levels of adhesion molecules in patients with SSc and IIM, in relation to the ILD and VE. <h3>Methods:</h3> All patients classified as having SSc between 2017-2018 at Institute of Rheumatology, Belgrade, Serbia or incident IIM cases between 1993-2014 at Rheumatology clinic, Karolinska University Hospital, Stockholm, Sweden were identified. After excluding patients with other comorbidities with the exception of arterial hypertension, our study enrolled 59/230 SSc patients (SSc-ILD, n=32), without any of macrovascular events, naïve for treatment with endothelin receptor antagonists, phosphodiesterase 5 inhibitors or prostanoids, and 129/246 IIM cases (IIM-ILD, n=40). ILD was confirmed either with Xray or HRCT and PFTs. ICAM1, E-selectin, and VCAM1 serum concentrations were measured by ELISA at either diagnosis (IIM) or at the time of inclusion to the study (SSc). An arterial and/or a venous TE ever occurred in the IIM group or ever experienced fingertips DUs over the course of disease in SSc cohort were considered as VE. <h3>Results:</h3> Patients with SSc-ILD (diffuseSSc n=19, limitedSSc n=13) or IIM-ILD (dermatomyositis n=13, polymyositis n=25, inclusion body myositis n=2), didn't differ in general demographic data, smoking status, age at disease onset and disease duration in comparison with those without ILD. ICAM1 was significantly elevated in the SSc-ILD cohort, while ICAM1 and E-selectin were increased in the IIM-ILD (p&lt;0.01, respectively),compared to non-ILD.ROC analysis confirmed that ICAM1 in SSc (AUC=0.673) and both ICAM1(AUC=0.638) and E-selectin (AUC=0.692) in the IIM showed good ability in discriminating cases with ILD from those without (p&lt;0.001, respectively). In both ILD groups, all investigated markers correlated among each other positively (p&lt;0.05, respectively), while a notable relation was observed between ICAM1 and E-selectin in non-ILD-IIM too (r=0.3, p=0.01). Applying multivariable logistic regression analysis, ICAM1 was found as an independent risk factor for SSc and IIM-ILD (OR 1.1 (1.02-1.2), p=0.004,OR1.1(1.01-1.2), p=0.04, respectively). The highest ICAM1 levels were found in SSc-ILD (n=18, Figure 1A) and IIM-ILD (n=10, Figure 1B) cohorts with VE (p&lt;0.001, respectively) compared to cases without VE despite the ILD status.ROC curves showed a good discriminatory ability of ICAM1 (p&lt;0.01,respectively, Figure 2) in identifying cases with VE among both ILD cohorts. <h3>Conclusion:</h3> Our study suggests role of the adhesion molecules in the pathogenesis of SSc and IIM-ILD. ICAM1 could be a novel risk biomarker for ILD development in both diseases, specifically identifying patients with vascular events and lung fibrosis. Thus, measuring ICAM1 in daily practice could help in the timely personalized management of patients at risk. <h3>REFERENCES:</h3> [1] A Notarnicola, S Barsotti, L Näsman, Q Tang, M Holmqvist, I E Lundberg, A Antovic. Evaluation of risk factors and biomarkers related to arterial and venous thrombotic events in idiopathic inflammatory myopathies. Scand J Rheumatol2021 Sep;50(5):390-397 [2] Chung WS, Lin CL, Sung FC, Hsu WH, Yang WT, Lu CC, et al. Systemic sclerosis increases the risks of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Rheumatology 2014;<b>53</b>:1639–45 [3] Jelena Colic, IvaPruner, Nemanja Damjanov, Tatjana Pekmezovic, MirjanaSefik-Bukilica, Aleksandra Antovic.Impaired Fibrinolysis Is Linked With Digital Vasculopathy and Onset of New Digital Ulcers in Systemic Sclerosis. J Rheumatol 2022 Jun;49(6):598-606 <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>