Circulating Citrullinated Vimentin Fragments Reflect Disease Burden in Ankylosing Spondylitis and Have Prognostic Capacity for Radiographic Progression

Abstract

Objective. Ankylosing spondylitis (AS) has been considered a seronegative rheumatic disease based on absent or low levels of antibodies against citrullinated proteins. The present study was undertaken to evaluate whether a citrullinated and matrix metalloproteinasedegraded fragment of vimentin (VICM) could be a prognostic biomarker in AS.Methods. VICM was measured in serum samples from healthy controls (n ‫؍‬ 35), control patients with rheumatoid arthritis (RA) (n ‫؍‬ 47), and patients with AS (n ‫؍‬ 201). The optimal cutoff for diagnostic sensitivity and specificity was determined by receiver operating characteristic curve analysis. Baseline and 2-year spine radiographs were available from 118 AS patients, and were scored using the modified Stoke AS Spine Score (mSASSS). We assessed correlations with patient demographic characteristics (age, disease duration), disease activity (Bath AS Disease Activity Index [BASDAI], C-reactive protein level), and disease severity (mSASSS) using Spearman's rho. The independent association of VICM with 2-year radiographic progression, defined as a change of >0 in the mSASSS or the development of a new syndesmophyte, was analyzed by multivariate regression.Results. Levels of degraded VICM were significantly higher in both RA patients and AS patients than in healthy controls (both P < 0.001). AS patients with the highest levels of VICM had the largest burden of disease (P < 0.01), i.e., highest mSASSS score and BASDAI. VICM levels were significantly and independently associated with radiographic progression after 2 years (␤ ‫؍‬ 0.69, P ‫؍‬ 0.0005). Patients with both a high VICM level and a high baseline mSASSS had the highest risk of radiographic progression (odds ratio 13 for mSASSS change, 32 for new syndesmophytes), with progression occurring in 67% of these patients.Conclusion. The present findings show that serum VICM may be of prognostic value in AS. The data also suggest that citrullination may be relevant in AS pathogenesis.

Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study

“…It is possible that the high levels of C1M, C4M, and VICM in the blood are results of a systemic effect where subjects with a general increased remodeling of the ECM and IF have a higher likelihood of developing cancer. Furthermore, all markers have been found elevated in a number of diseases characterized by ECM remodeling and tissue inflammation and are, therefore, not specific to cancer (7)(8)(9)(36)(37)(38)(39). Finally, it needs to be elucidated if the results of this study can be applied to populations of other ages and ethnic backgrounds and if the biomarkers are more useful for certain types of solid cancer.…”

Fragments of Citrullinated and MMP-degraded Vimentin and MMP-degraded Type III Collagen Are Novel Serological Biomarkers to Differentiate Crohn’s Disease from Ulcerative Colitis

“…22 Another interesting protein is vimentin, a type III intermediate filament protein, which has recently been demonstrated to be involved in the pathogenesis of IBD. 23 Furthermore, vimentin have shown diagnostic relevance in other inflammatory diseases including rheumatoid arthritis 24 and ankylosing spondylitis, 25 as well as in several forms of cancer. 26 Biomarker assays measuring specific neo-epitopes of vimentin (MMP-2 and MMP-8 degraded and citrullinated-vimentin [VICM]), 27 31,32 have shown promise as diagnostic tools in several autoimmune diseases 24,25,33,34,35 and in fibrosis.…”

The ASAS Criteria for Axial Spondyloarthritis: Strengths, Weaknesses, and Proposals for a Way Forward

“…(Hamlet, William Shakespeare). [39,40] • Proteonomics [43] • Specific Biomarkers Vascular endothelium growth factor [44] Matrix metalloproteinase-3 [45,46] Sclerostin [47,48] Calprotectin [49] Citrullinated vimentin [50] Dikkopf-1 [51] Anti-CD74 antibodies [52][53][54] 56.•• van Tubergen A. The changing clinical picture and epidemiology of spondyloarthritis.…”

“…Appropriate assessment of criterion validity of the Bconstruct^axSpA would include verification of its biologic association with AS genetics, including MHC and non-MHC gene variants, and proteomic or other biomarkers that turn out to be typical for and occur frequently in classical AS. Candidate biomarkers, mostly hypothetical at this stage, are listed in Table 6 [39,40,[43][44][45][46][47][48][49][50][51][52][53][54]. Some of these biomarkers may turn out to have prognostic value, and those will be most suitable as predictors of outcome, not as candidates for classification criteria that are intended to create homogeneity, not prognostication.…”