THU0272 BASEMENT MEMBRANE SEROLOGICAL MARKERS OF COLLAGEN TYPE IV AND LAMININ REMODELING ARE DIFFERENTIALLY EXPRESSED IN SLE
Authors: S. D. Kay, F. Genovese, A. S. Siebuhr, M. Karsdal, A. Voss, P. Junker
Journal: Annals of the Rheumatic Diseases (2020)

Background: Collagen type IV and laminin are the main constituents of basement membranes (BMs). Epitopes on these molecules are targeted in various autoimmune diseases, systemic lupus erythematosus (SLE) in particular. Accelerated large vessel disease is a well-recognized cause of premature cardiovascular morbidity and mortality in SLE. Novel tools for quantification of soluble MMP-derived fragments of collagen type IV (C4M) and laminin (LG1M) have emerged as promising biomarkers for BM remodeling in atherosclerosis. Objectives: To study serum levels of collagen type IV and laminin metabolites in patients with SLE and in healthy controls. And to search for associations with disease activity, organ damage and cardiovascular comorbidity. Methods: One hundred and six SLE patients without and 20 with previous CVD events were included (1). One hundred and twenty male and female blood donors aged 20-65 years served as healthy reference. Disease activity (SLEDAI) and damage (SLICC) scores were calculated. Coronary artery calcification (CAC) was studied by CT scan and expressed as Agatston score. Carotid intima-media thickness (IMT) was measured by ultrasound (LOGIQ E9, GE Healthcare). In either subgroup atherosclerosis was defined as Agatston &gt; 99 U and/or IMT&gt;1 mm and/or presence of plaque. C4M and LG1M were measured by competitive ELISAs (2). Results: Patient characteristics are presented in Table 1. Overall, C4M and LG1M were significantly increased in the entire SLE cohort vs. healthy controls (35.7 ± 17.5 vs. 22.3 ± 9.4 ng/mL, p&lt;0.0001 and 20.9 ± 21.1 vs. 9.7 ± 8.0 ng/mL, p&lt;0.0001, respectively) (Fig 1). Highly significant positive correlations were detected between C4M and LG1M in the entire SLE cohort and in the healthy control group (Fig 2).In terms of CVD and atherosclerosis LG1M was significantly higher in SLE patients with manifest CVD vs. those without (34.47 ± 41.22 vs. 18.34 ± 13.55, p=0.0015) and in those with atherosclerosis by imaging (25.53 ± 28.12 vs 17.53 ± 13.35, p=0.036). There were no associations between C4M and CVD or atherosclerosis. There was a weak association between LG1M and SLICC (r=0.22, p=0.01), but not with SLEDAI. Details on associations with other CVD risk factors and specific organ involvement will be presented. Table 1 Characteristics for SLE patients with and without CVD Patients characteristics All (126) SLE + CVD (20) SLE without CVD (106) p Females, no. (%) 113 (89) 18 (90) 95 (89) 0.95 Age, yrs., mean ± SD 50.6± 14.4 54.8 ± 15.3 46.8± 14.1 0.15 Disease duration, yrs., mean ± SD 13.9 ± 9.3 19.0± 11.3 13.0± 11.3 0.007 SLEDAI, median, range 4 (0-14) 4 (0-10) 4 (0-14) 0.717 SLICC, median, range 1 (0-11) 3 (1-11) 1 (0-10) 0.0001 Atherosclerosis, no. (%) 53 (42) 14 (70) 39 (37) 0.0006 LG1M (ng/ml), mean ± SD 20.9± 21.2 34.5± 41.2 18.3 ± 13.6 0.0015 C4M (ng/ml), mean ± SD 35.7 ± 17.5 38.1± 20.6 35.3± 16.9 0.518 Conclusion: Serological levels of collagen type IV and laminin biomarkers were elevated and interrelated in an unstratified SLE population. Moreover, LG1M but not C4M was significantly elevated in SLE patients with previous CVD events and in those with atherosclerosis by imaging. These findings indicate that LG1M may serve as a serological marker for SLE-related large vessel disease. However, additional extravascular sites of increased basement membrane remodeling may contribute to the abnormal biomarker pattern. References: [1]Kay SD, Poulsen MK, Diederichsen AC, Voss A. J Rheumatol 2016;43:315–22 [2]Sand JM, Larsen L, Hogaboam C et al. PLoS One 2013;8:e84934 Kay SD and Genovese F contributed equally to this work. Figure 1. Levels of C4M and LG1M in serum of patients with SLE and healthy controls; graphs are presented as box and whiskers plot (in the style of Tukey). Statistical significance: ****p&lt;0.0001. Figure 2. Correlation plots (Spearman r) of C4M and LG1M in SLE patients and healthy controls. Disclosure of Interests: Susan Due Kay: None declared, Federica Genovese Shareholder of: Own Nordic Bioscience stocks, Employee of: Nordic Bioscience, Anne Sofie Siebuhr Employee of: Nordic Bioscience, Morten Karsdal Shareholder of: Nordic Bioscience A/S., Employee of: Full time employee at Nordic Bioscience A/S., Anne Voss: None declared, Peter Junker: None declared