Background/Purpose: Rheumatoid arthritis (RA) is considered an anti-CCP positive disease whereas ankylosing spondylitis (AS) is considered an anti-CCP negative disease. Anti-CCP has prognostic capacity in RA. Assessment of metalloproteinases (MMP) may also add prognostic information in both diseases. We evaluated whether a citrullinated and MMP degraded fragment of vimentin (VICM) could be used as an in vitro diagnostic and prognostic biomarker in AS.

Methods: Serum VICM was measured in samples of controls (n=35), RA (n=47) and AS (n=201) patients. Optimal cut-off for diagnostic sensitivity and specificity was determined by ROC analysis. Baseline and 2-year spinal radiographs were available on 118 AS patients and radiographic progression was scored using the mSASSS. Correlations with patient demographics (age, disease duration), disease activity (BASDAI, CRP, SPARCC MRI Spine 23-DVU score), and severity (mSASSS), were determined. The independent association of VICM with 2-year radiographic progression, defined as mSASSS change>0 or the development of a new syndesmophyte, was analyzed by multivariate regression adjusting for baseline mSASSS.

Results: Both RA and AS had significantly higher levels of VICM than controls (p<0.001). AS patients with the highest level of VICM had the largest burden of disease i.e. highest mSASSS score and disease activity (BASDAI) (p < 0.001). VICM correlated significantly with SPARCC MRI Spine 23DVU score (p = 0.046). VICM was significantly and independently associated with radiographic progression after 2 years (β = 0.69, p=0.0005). Patients with both high VICM and a high baseline mSASSS had the highest risk for radiographic progression (OR for mSASSS change = 13, new syndesmophyte = 32) and 67% of these had progression (figure).

Conclusion: Serum VICM is a diagnostic and prognostic marker for AS. Moreover, our data challenges the paradigm that AS is an Anti-CCP negative disease.