Mutated citrullinated vimentin

Detection of autoantibodies against mutated citrullinated vimentin is part of RA diagnostics (rheumatoid arthritis), especially in sera negative for rheumatoid factor (RF negative sera). Anti-MCV antibodies are member of ACPA family, a group of the so called antibodies to citrullinated protein/peptide antigens.

Rheumatoid arthritis is an autoimmune disorder. Detection of specific autoantibodies (antibodies directed against the body’s own tissue) such as rheumatoid factors and ACPAs may provide indication of the disease. In many cases, autoimmune diagnostics are crucial for diagnosing RA correctly and already in the disease’s early stages, when typical symptoms often are lacking but when medical therapy is most effective.

Basics

Citrullination of proteins permanently takes place in cell metabolism. It is considered as a body’s own effect. At this a certain amino acid (arginine) is converted into citrulline, an atypical amino acid. The modified (citrullinated) protein is assumed to be foreign to the body, and auto-reactive antibodies directed against the body’s own structures are brought out. These auto-antibodies get inflammation response going, what will result in autoimmune disorder.^[1]

Various kinds of citrullinated proteins have been detected in the joints of RA patients. One of these is Sa antigen,^[2] now known as mutated citrullinated vimentin (MCV).

Citrullination of vimentin plays a decisive role in RA pathogenesis.

Significance

point-of-care testing for rheumatoid arthritis using the rheumachec rapid test

In rheumatology diagnostics, autoantibodies against mutated citrullinated vimentin (anti-MCV) are of prominent diagnostic and prognostic value.^[3] Their significance is greater than that of rheumatoid factor.

Recently a serological point-of-care test (POCT) for the early detection of RA has been developed. This assay combines the detection of rheumatoid factor and anti-MCV for diagnosis of rheumatoid arthritis and shows a sensitivity of 72% and specificity of 99.7%.^[4][5]

Anti-MCV are used as efficient biomarkers for estimating progress of rheumatoid arthritis.^[6] Main advantage of testing for anti-MCV is the early appearance of the anti-MCV antibodies, what allows for detection of early RA and submits adequate therapy just after the disease’s onset. Moreover, anti-MCV titres show strong correlation to disease activity, disease severity and the success of therapy.^[7][8]

References

1. ^ György B, Tóth E, Tarcsa E, Falus A, Buzás EI. Citrullination: A posttranslational modification in health and disease. Int J Biochem Cell Biol. 2006;38(10):1662-77. Epub 2006 Mar 30. Review. abstract
2. ^ Després N, Boire G, Lopez-Longo FJ, Ménard HA. The Sa system: a novel antigen-antibody system specific for rheumatoid arthritis. J Rheumatol. 1994 Jun;21(6):1027-33: abstract
3. ^ From Speculation to Confirmation in early RA. Summarizing eight peer reviewed studies:www.avisetest.com
4. ^ Renger F, Bang H, Fredenhagen G, Natusch A, Backhaus M, Feist E, Egerer K, Burmester GR. "Anti-MCV Antibody Test for the Diagnosis of Rheumatoid Arthritis Using a POCT-Immunoassay". American College of Rheumatology, 2008 Annual Scientific Meeting, poster presentation. http://acr.confex.com/acr/2008/webprogram/Paper2009.html. 
5. ^ Luime JJ, Colin EM, Hazes JM, Lubberts E. (2010). "Does anti-MCV has additional value as serological marker in the diagnostic and prognostic work-up of patients with rheumatoid arthritis? A systematic review.". Ann Rheum Dis. 2009 Mar 15. [Epub ahead of print] 69 (2): 337–44. doi:10.1136/ard.2008.103283. PMID 19289382. http://ard.bmj.com/cgi/rapidpdf/ard.2008.103283v1. 
6. ^ Bang H, Egerer K, Gauliard A, Lüthke K, Rudolph PE, Fredenhagen G et al.: Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. (2007) 56(8): S. 2503-2511 full text
7. ^ Roland PN, Mignot SG, Bruns A, Hurtado M, Palazzo E, Havem G, Dieudé P, Meyer O, Martin SC. Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthritis Res Ther. 2008 Dec 10;10(6):R142. – doi:10.1186/ar2570: full text
8. ^ Mathsson L, Mullazehi M, Wick MC, Sjoberg O, van VR, Klareskog L et al. Antibodies against citrullinated vimentin in rheumatoid arthritis: Higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. Arthritis Rheum 2007; 58(1):36-45. – doi:10.1002/art.23188 full text