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.
Disclosure of Interest None declared
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