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Predicting Arthritis Outcome: Anti-MCV for Monitoring Subclinical Atherosclerosis in Rheumatoid Arthritis

Antibodies to Modified Citrullinated Vimentin Are Associated with Subclinical Atherosclerosis in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease (CVD), especially accelerated atherosclerosis (1-3). There is evidence that this already occurs early in the disease process. Well known common CVD risk factors interact with the systemic auto-inflammatory response during the disease process and speed up the development of atherosclerosis in patients suffering from rheumatoid arthritis. heartbeat

Antibodies against citrullinated protein and peptide antigens (ACPA) are highly sensitive and specific markers for early rheumatoid arthritis. Antibodies to Modified Citrullinated Vimentin (anti-MCV) predict poor outcome and appear to play a major role in the pathogenesis of rheumatoid arthritis. 

A recently published study by Amal El-Barbary and his co-workers may now shed light on the relationship between anti-MCV antibodies and cardiovascular co-morbidities in patients with rheumatoid arthritis (4). They investigated the correlation of anti-MCV antibodies in early RA with disease activity and cardiovascular risk factors compared to antibodies against cyclic citrullinated peptides (anti-CCP3).

A. M. El-Barbary, E. M. Kassem, M. A. El-Sergany, S. A. Essa, and M. A. Eltomey. Association of Anti-Modified Citrullinated Vimentin with Subclinical Atherosclerosis in Early Rheumatoid Arthritis Compared with Anti-Cyclic Citrullinated Peptide. J Rheumatol, 2011, 38(5):828-34

The Egyptian researchers measured antibody concentrations in 100 patients with early RA and 100 healthy subjects to determine sensitivity and specificity of the anti-MCV and the anti-CCP tests.

Anti-MCV, anti-CCP, rheumatoid factor (RF), disease activity score (DAS 28), lipid profile, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), insulin resistance (HOMA-IR), tumour necrosis factor alpha (TNF-alpha), interleukin 6 (Il-6) and carotid intima-media thickness (cIMT) were determined before and after 12 months of treatment with methotrexate (MTX) and prednisone.

Values of carotid intima-media thickness are closely linked to local and systemic atherosclerosis and  clinical cardiovascular endpoints (5-7). cIMT as a marker for early atherosclerotic changes can be assessed by non-invasive ultrasound methods.

Anti-MCV and anti-CCP are similarly helpful for initial diagnosis

The study demonstrated, that values for anti-MCV and anti-CCP3 correlated well, and the two assays showed comparable sensitivity and specificity for the diagnosis of early rheumatoid arthritis.

At baseline, anti-MCV titres and anti-CCP3 titres were related to CRP, Il-6, HOMA-IR, serum RF-level and cIMT. The levels of all biochemical markers were significantly higher and carotid intima-media thickness was significantly greater in RA patients than in healthy subjects, suggesting that RA patients with circulating ACPA show signs of accelerated subclinical atherosclerosis and may suffer a more aggressive disease (8).

Changes of anti-MCV levels parallel changes in clinical and laboratory parameters in response to therapy

After 12 months of treatment with MTX and prednisone a significant decrease of serum anti-MCV and anti-CCP3 was observed.

However, only alterations in anti-MCV levels correlated significantly with changes of clinical or biochemical variables related to disease activity. Variation of anti-CCP levels was not significantly linked to these parameters. Especially changes in CV risk factors, CRP, Il6, TNF-alpha, HOMA-IR and cIMT were strongly associated with changes in anti-MCV concentrations.

 These observations suggest, that changes of anti-MCV titers in response to treatment with MTX reflect an improvement in subclinical atherosclerosis. The considerable decrease of Anti-MCV in association with amelioration of clinical symptoms reveals that anti-MCV might be a more sensitive indicator for disease activity than anti-CCP.

In conclusion the results of the study evidence that anti-MCV is a highly sensitive and specific marker for diagnosing RA. Moreover, determination of anti-MCV levels indicates response to MTX therapy and may be useful for monitoring subclinical atherosclerosis in early rheumatoid arthritis.

References: 

1. T. M. Farragher, N. J. Goodson, H. Naseem, A. J. Silman, W. Thomson, D. Symmons, and A. Barton. Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis.  Arthritis Rheum 58 (2):359-369, 2008.  (link to full text)

2. Z. Szekanecz and A. E. Koch. Vascular involvement in rheumatic diseases: ‘vascular rheumatology’. Arthritis Res.Ther. 10 (5):224, 2008. (link to full text)

3. H. Pieringer and M. Pichler. Cardiovascular morbidity and mortality in patients with rheumatoid arthritis: vascular alterations and possible clinical implications. QJM. 104 (1):13-26, 2011.  (link to abstract)

4. A. M. El-Barbary, E. M. Kassem, M. A. El-Sergany, S. A. Essa, and M. A. Eltomey. Association of Anti-Modified Citrullinated Vimentin with Subclinical Atherosclerosis in Early Rheumatoid Arthritis Compared with Anti-Cyclic Citrullinated Peptide. J Rheumatol, 2011. (link to abstract)

5. M. W. Lorenz, H. S. Markus, M. L. Bots, M. Rosvall, and M. Sitzer. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115 (4):459-467, 2007. (link to full text)

6. A. Sodergren, K. Karp, K. Boman, C. Eriksson, E. Lundstrom, T. Smedby, L. Soderlund, S. Rantapaa-Dahlqvist, and S. Wallberg-Jonsson. Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness. Arthritis Res Ther 12 (4):R158, 2010. (link to full text)

7. P. N. Tyrrell, J. Beyene, B. M. Feldman, B. W. McCrindle, E. D. Silverman, and T. J. Bradley. Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arterioscler.Thromb.Vasc.Biol 30 (5):1014-1026, 2010.  (link to full text)

8. T. M. Farragher, D. Plant, E. Flynn, S. Eyre, D. Bunn, W. Thomson, D. Symmons, and A. Barton. Association of a rheumatoid arthritis susceptibility variant at the CCL21 locus with premature mortality in inflammatory polyarthritis patients. Arthritis Care Res (Hoboken.) 62 (5):676-682, 2010. (link to full text)

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