Serological markers of basement membrane collagen type IV and laminin are increased in systemic lupus erythematosus but differentially expressed in patients with previous cardiovascular events

Objective To assess basement membrane remodelling in systemic lupus erythematosus (SLE) by studying serum levels of type IV collagen (C4M) and laminin (LG1M) fragments and their association with disease profile. Methods One hundred and six SLE patients without and 20 with previous cardiovascular events were included. One hundred and twenty male and female blood donors served as controls. Disease Activity Score (SLEDAI-2K) and cumulated Damage Index (SLICC-DI) were calculated. Coronary artery calcification (CAC) was studied by CT scan. Carotid intima-media thickness (IMT) was measured by ultrasound. C4M and LG1M were quantified by ELISAs. Results Serum levels of LG1M and C4M were significantly increased in the entire SLE cohort, median (IQR) 15.8 (26.16) ng/ml vs. 5.5 (5.8) ng/ml (+/- 9.4), p<0.0001 and 31.3 (20.0) vs. 21.6 (9.2) ng/ml, p<0.0001. C4M and LG1M were mutually interrelated in patients and controls, r=0.44 (p<0.0001) and r=0.42 (p<0.0001). LG1M was significantly higher in patients with previous cardiovascular events (CVE), 27.2 (30.8) vs. 14.1 (21.4) p<0.03, while C4M did not differ between these subsets. LG1M, but not C4M, was borderline higher in anti-phospholipid antibody -positive patients vs. negatives (p=0.08). There was a weak correlation between LG1M and SLICC-DI, r=0.22 (p=0.01), but no associations between these markers and criterial lupus manifestations or asymptomatic atherosclerosis. Conclusion These findings indicate that remodelling of collagen type IV and laminin is increased in SLE unrelated to disease activity, presumably reflecting clinically silent disease progression. The selective association of increased LG1M and cardiovascular events may represent a distinctive aspect of SLE-related vessel wall repair.