SAT0283 Antibodies to carbamylated vimentin in patients with systemc lupus erythematosus are associated with renal involvenment

Abstract

Background: Vimentin is a cytoskeleton protein of the intermediate filaments family, expressed by mesenchymal cells including vascular endothelial cells and renal tubular cells. Vimentin has been recently proposed as a target of the in situ immune response in lupus nephritis. Antibodies to vimentin have been described in 10-53% of patients with Systemic Lupus Erythematosus (SLE) and account for a fibrous pattern of cytoplasmic immunofluorescence. Post-translational modifications increase the immunogenicity of vimentin, as demonstrated by the detection of anti-modified vimentin antibodies in patients with rheumatoid arthritis. Carbamylation is a non-enzymatic post-translational modification consisting in the addition of a cyanate group on lysine and arginine residues; since carbamylation is time dependent, structural proteins with a slow turnover are more likely to be carbamylated. The role of carbamylated vimentin as an antigenic target in SLE has not been yet evaluated. Objectives: Aims of the study were to assess the prevalence of anti-carbamylated vimentin in a cohort of SLE patients and to evaluate the possible associations with clinical and serological feature of the disease. Methods: Patients with SLE classified according to 1987 ACR criteria were enrolled. Clinical features, autoantibodies profile and disease activity - as measured by SLE Disease Activity Index 2000 (SLEDAI 2K) - were collected. Sera obtained from each patient were tested for anti-carbamylated vimentin by a home-made enzyme-linked immunoassay. Data were expressed as mean±standard deviation or median (interquartile range) when appropriate. To investigate difference in anti-carbamylated vimentin prevalence and anti-carbamylated vimentin serum levels Mann-Whitney and Chi square test were applied. P value <0.05 was considered statistically significant. Results: We enrolled 109 SLE patients (102F:7M, mean age 39.4±12.6 years, mean disease duration 10.5±9.5 years, mean SLEDAI 2K 5±5.5). Overall, 30 out of 109 patients (27.5%) were positive for anti-carbamylated vimentin. According to the clinical features, the prevalence of anti-carbamylated vimentin was significantly higher in patients with lupus nephritis (18/44) compared to those without renal involvement (12/66) (41.8% vs 18.2%, p=0.006); moreover, anti-carbamylated vimentin serum levels were significantly higher in patients with lupus nephritis [2561 (1783) OD] compared to those without [1970 (1123) OD; p=0.0178]. We didn't find any difference in prevalence or titre of anti-carbamylated vimentin according to presence/absence of other clinical manifestations (musculoskeletal, muco-cutaneous, hematologic, neuropsychiatric) or serology (low complement, anti-dsDNA). Moreover, we did not find any correlation between anti-carbamylated vimentin serum levels and SLEDAI 2K. Conclusions: Higher prevalence and serum levels of anti-carbamylated vimentin antibodies in patients with lupus nephritis confirm the role of vimentin as a target of the immune response in patients with glomerulonephritis and suggest their possible role as a biomarker of kidney involvement in SLE patients.