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Erschienen in: Zeitschrift für Rheumatologie 10/2015

01.12.2015 | Originalien

Diagnostic accuracy of anti-MCV and anti-CCP antibodies in rheumatoid arthritis

A meta-analysis

verfasst von: Y.H. Lee, MD, PhD, S.-C. Bae, G.G. Song

Erschienen in: Zeitschrift für Rheumatologie | Ausgabe 10/2015

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Abstract

Objective

The purpose of this study was to compare the diagnostic performance of anti-mutated citrullinated vimentin (anti-MCV) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in rheumatoid arthritis (RA).

Methods

We searched the Medline, Embase, and Cochrane library databases and performed two meta-analyses on the diagnostic accuracy of anti-MCV and anti-CCP in patients with RA compared to healthy controls.

Results

We identified 12 studies that included a total of 2003 RA patients and 831 healthy controls for the meta-analysis. The pooled sensitivity and specificity of anti-MCV were 68.6 % [95 % confidence interval (CI) 66.6–79.7] and 94.2 % (95 % CI 92.4–96.7) and those of anti-CCP were 61.7 % (95 % CI 59.5–63.8) and 97.1 % (95 % CI 96.7–98.1), respectively. Anti-MCV PLR, NLR, and DOR were 12.99 (95 % CI 8.013–21.27), 0.297 (95 % CI 0.238–0.369), and 47.78 (95 % CI 28.59–79.84), and those for anti-CCP were 16.71 (95 % CI 11.42–24.47), 0.378 (95 % CI 0.325–0.439), and 54.20 (95 % CI 31.65–92.82), respectively. The AUC of anti-MCV was 0.886, and its Q* index was 0.817, indicating modest accuracy, while the AUC of anti-CCP was 0.946, and its Q* index was 0.885. The sensitivity of anti-MCV was significantly higher than that of anti-CCP in the diagnosis of RA (difference 0.069, 95 % CI 0.039–0.098, p < 0.0001), but the specificity of anti-MCV was lower than that of anti-CCP (difference − 0.029, 95 % CI − 0.051 to − 0.006, p = 0.012). The Q* index of anti-MCV was significantly lower than that of anti-CCP (difference − 0.068, 95 % CI − 0.070 to − 0.065, p < 0.0001).

Conclusion

Our meta-analysis demonstrates that anti-MCV is more sensitive but less specific, and has lower diagnostic accuracy than anti-CCP in RA, although anti-MCV and anti-CCP showed comparable high PLRs.
Literatur
2.
Zurück zum Zitat Lard LR, Visser H, Speyer I et al (2001) Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 111(6):446–451CrossRefPubMed Lard LR, Visser H, Speyer I et al (2001) Early versus delayed treatment in patients with recent-onset rheumatoid arthritis: comparison of two cohorts who received different treatment strategies. Am J Med 111(6):446–451CrossRefPubMed
3.
Zurück zum Zitat Dorner T, Egerer K, Feist E, Burmester GR (2004) Rheumatoid factor revisited. Curr Opin Rheumatol 16(3):246–253CrossRefPubMed Dorner T, Egerer K, Feist E, Burmester GR (2004) Rheumatoid factor revisited. Curr Opin Rheumatol 16(3):246–253CrossRefPubMed
4.
Zurück zum Zitat Schellekens GA, Jong BA de, Hoogen FH van den et al (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101(1):273–281PubMedCentralCrossRefPubMed Schellekens GA, Jong BA de, Hoogen FH van den et al (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101(1):273–281PubMedCentralCrossRefPubMed
5.
Zurück zum Zitat Boekel MA van, Vossenaar ER, Hoogen FH van den, Venrooij WJ van (2002) Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res 4(2):87–93PubMedCentralCrossRefPubMed Boekel MA van, Vossenaar ER, Hoogen FH van den, Venrooij WJ van (2002) Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value. Arthritis Res 4(2):87–93PubMedCentralCrossRefPubMed
6.
Zurück zum Zitat Vossenaar ER, Zendman AJ, Venrooij WJ van, Pruijn GJ (2003) PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25(11):1106–1118CrossRefPubMed Vossenaar ER, Zendman AJ, Venrooij WJ van, Pruijn GJ (2003) PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 25(11):1106–1118CrossRefPubMed
7.
Zurück zum Zitat Schellekens GA, Visser H, Jong BA de et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43(1):155–163CrossRefPubMed Schellekens GA, Visser H, Jong BA de et al (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43(1):155–163CrossRefPubMed
8.
Zurück zum Zitat Mor-Vaknin N, Punturieri A, Sitwala K, Markovitz DM (2003) Vimentin is secreted by activated macrophages. Nat Cell Biol 5(1):59–63CrossRefPubMed Mor-Vaknin N, Punturieri A, Sitwala K, Markovitz DM (2003) Vimentin is secreted by activated macrophages. Nat Cell Biol 5(1):59–63CrossRefPubMed
9.
Zurück zum Zitat Bang H, Egerer K, Gauliard A et al (2007) Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum 56(8):2503–2511CrossRefPubMed Bang H, Egerer K, Gauliard A et al (2007) Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum 56(8):2503–2511CrossRefPubMed
10.
Zurück zum Zitat Vossenaar ER, Despres N, Lapointe E et al (2004) Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther 6(2):R142–R150PubMedCentralCrossRefPubMed Vossenaar ER, Despres N, Lapointe E et al (2004) Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res Ther 6(2):R142–R150PubMedCentralCrossRefPubMed
11.
Zurück zum Zitat Hueber W, Hassfeld W, Smolen JS, Steiner G (1999) Sensitivity and specificity of anti-Sa autoantibodies for rheumatoid arthritis. Rheumatology (Oxford) 38(2):155–159 Hueber W, Hassfeld W, Smolen JS, Steiner G (1999) Sensitivity and specificity of anti-Sa autoantibodies for rheumatoid arthritis. Rheumatology (Oxford) 38(2):155–159
12.
Zurück zum Zitat Luime JJ, Colin EM, Hazes JM, Lubberts E (2010) Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis 69(2):337–344CrossRefPubMed Luime JJ, Colin EM, Hazes JM, Lubberts E (2010) Does anti-mutated citrullinated vimentin have additional value as a serological marker in the diagnostic and prognostic investigation of patients with rheumatoid arthritis? A systematic review. Ann Rheum Dis 69(2):337–344CrossRefPubMed
13.
Zurück zum Zitat Zhu T, Feng L (2013) Comparison of anti-mutated citrullinated vimentin, anti-cyclic citrullinated peptides, anti-glucose-6-phosphate isomerase and anti-keratin antibodies and rheumatoid factor in the diagnosis of rheumatoid arthritis in Chinese patients. Int J Rheum Dis 16(2):157–161CrossRefPubMed Zhu T, Feng L (2013) Comparison of anti-mutated citrullinated vimentin, anti-cyclic citrullinated peptides, anti-glucose-6-phosphate isomerase and anti-keratin antibodies and rheumatoid factor in the diagnosis of rheumatoid arthritis in Chinese patients. Int J Rheum Dis 16(2):157–161CrossRefPubMed
14.
Zurück zum Zitat Al-Shukaili A, Al-Ghafri S, Al-Marhoobi S, Alkaabi J (2012) Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated Peptide antibodies and rheumatoid factor in omani patients with rheumatoid arthritis. Int J Rheumatol 2012:285854PubMedCentralCrossRefPubMed Al-Shukaili A, Al-Ghafri S, Al-Marhoobi S, Alkaabi J (2012) Evaluation of anti-mutated citrullinated vimentin antibodies, anti-cyclic citrullinated Peptide antibodies and rheumatoid factor in omani patients with rheumatoid arthritis. Int J Rheumatol 2012:285854PubMedCentralCrossRefPubMed
15.
Zurück zum Zitat Damjanovska L, Thabet MM, Levarth EW et al (2010) Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis 69(4):730–732CrossRefPubMed Damjanovska L, Thabet MM, Levarth EW et al (2010) Diagnostic value of anti-MCV antibodies in differentiating early inflammatory arthritis. Ann Rheum Dis 69(4):730–732CrossRefPubMed
16.
Zurück zum Zitat Mutlu N, Bicakcigil M, Tasan DA et al (2009) Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis. J Rheumatol 36(3):491–500CrossRefPubMed Mutlu N, Bicakcigil M, Tasan DA et al (2009) Comparative performance analysis of 4 different anti-citrullinated protein assays in the diagnosis of rheumatoid arthritis. J Rheumatol 36(3):491–500CrossRefPubMed
17.
Zurück zum Zitat Mathsson L, Mullazehi M, Wick MC et al (2008) 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 58(1):36–45CrossRefPubMed Mathsson L, Mullazehi M, Wick MC et al (2008) 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 58(1):36–45CrossRefPubMed
18.
Zurück zum Zitat Diaz-Toscano ML, Olivas-Flores EM, Zavaleta-Muniz SA et al (2014) Comparison of two assays to determine anti-citrullinated peptide antibodies in rheumatoid arthritis in relation to other chronic inflammatory rheumatic diseases: assaying anti-modified citrullinated vimentin antibodies adds value to second-generation anti-citrullinated cyclic peptides testing. Biomed Res Int 2014:198198PubMedCentralCrossRefPubMed Diaz-Toscano ML, Olivas-Flores EM, Zavaleta-Muniz SA et al (2014) Comparison of two assays to determine anti-citrullinated peptide antibodies in rheumatoid arthritis in relation to other chronic inflammatory rheumatic diseases: assaying anti-modified citrullinated vimentin antibodies adds value to second-generation anti-citrullinated cyclic peptides testing. Biomed Res Int 2014:198198PubMedCentralCrossRefPubMed
19.
Zurück zum Zitat El-Barbary AM, Kassem EM, El-Sergany MA et al (2011) Association of anti-modified citrullinated vimentin with subclinical atherosclerosis in early rheumatoid arthritis compared with anti-cyclic citrullinated peptide. J Rheumatol 38(5):828–834CrossRefPubMed El-Barbary AM, Kassem EM, El-Sergany MA et al (2011) Association of anti-modified citrullinated vimentin with subclinical atherosclerosis in early rheumatoid arthritis compared with anti-cyclic citrullinated peptide. J Rheumatol 38(5):828–834CrossRefPubMed
20.
Zurück zum Zitat Liu X, Jia R, Zhao J, Li Z (2009) The role of anti-mutated citrullinated vimentin antibodies in the diagnosis of early rheumatoid arthritis. J Rheumatol 36(6):1136–1142CrossRefPubMed Liu X, Jia R, Zhao J, Li Z (2009) The role of anti-mutated citrullinated vimentin antibodies in the diagnosis of early rheumatoid arthritis. J Rheumatol 36(6):1136–1142CrossRefPubMed
21.
Zurück zum Zitat Innala L, Kokkonen H, Eriksson C et al (2008) Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides. J Rheumatol 35(6):1002–1008PubMed Innala L, Kokkonen H, Eriksson C et al (2008) Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides. J Rheumatol 35(6):1002–1008PubMed
22.
Zurück zum Zitat Soos L, Szekanecz Z, Szabo Z et al (2007) Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis. J Rheumatol 34(8):1658–1663PubMed Soos L, Szekanecz Z, Szabo Z et al (2007) Clinical evaluation of anti-mutated citrullinated vimentin by ELISA in rheumatoid arthritis. J Rheumatol 34(8):1658–1663PubMed
23.
Zurück zum Zitat Nicaise Roland P, Grootenboer Mignot S, Bruns A et al (2008) Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthritis Res Ther 10(6):R142CrossRef Nicaise Roland P, Grootenboer Mignot S, Bruns A et al (2008) Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy. Arthritis Res Ther 10(6):R142CrossRef
24.
Zurück zum Zitat Song JS, Park GB, Park AJ (2007) Comparison of anti-mutated citrullinated vimentin with anti-cyclic citrullinated peptide and rheumatoid factors for the diagnostic value of rheumatoid arthritis. Korean Rheum Assoc 14:235–241CrossRef Song JS, Park GB, Park AJ (2007) Comparison of anti-mutated citrullinated vimentin with anti-cyclic citrullinated peptide and rheumatoid factors for the diagnostic value of rheumatoid arthritis. Korean Rheum Assoc 14:235–241CrossRef
25.
Zurück zum Zitat Lee YH, Bae SC, Choi SJ et al (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38(6):3643–3651CrossRefPubMed Lee YH, Bae SC, Choi SJ et al (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38(6):3643–3651CrossRefPubMed
26.
Zurück zum Zitat Lee YH, Rho YH, Choi SJ et al (2006) Association of TNF-alpha − 308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int 27(2):157–161CrossRefPubMed Lee YH, Rho YH, Choi SJ et al (2006) Association of TNF-alpha − 308 G/A polymorphism with responsiveness to TNF-alpha-blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int 27(2):157–161CrossRefPubMed
27.
Zurück zum Zitat Lee YH, Rho YH, Choi SJ et al (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27(9):827–833CrossRefPubMed Lee YH, Rho YH, Choi SJ et al (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27(9):827–833CrossRefPubMed
28.
Zurück zum Zitat Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097PubMedCentralCrossRefPubMed Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097PubMedCentralCrossRefPubMed
29.
Zurück zum Zitat Whiting P, Rutjes AW, Reitsma JB et al (2003) The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 3:25PubMedCentralCrossRefPubMed Whiting P, Rutjes AW, Reitsma JB et al (2003) The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 3:25PubMedCentralCrossRefPubMed
30.
Zurück zum Zitat Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558CrossRefPubMed Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558CrossRefPubMed
32.
Zurück zum Zitat DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefPubMed DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefPubMed
33.
Zurück zum Zitat Lijmer JG, Bossuyt PM, Heisterkamp SH (2002) Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med 21(11):1525–1537CrossRefPubMed Lijmer JG, Bossuyt PM, Heisterkamp SH (2002) Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med 21(11):1525–1537CrossRefPubMed
34.
Zurück zum Zitat Walter SD (2002) Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med 21(9):1237–1256CrossRefPubMed Walter SD (2002) Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med 21(9):1237–1256CrossRefPubMed
36.
Zurück zum Zitat Besada E, Nikolaisen C, Nossent JC (2011) Diagnostic value of antibodies against mutated citrullinated vimentin for rheumatoid arthritis. Clin Exp Rheumatol 29(1):85–88PubMed Besada E, Nikolaisen C, Nossent JC (2011) Diagnostic value of antibodies against mutated citrullinated vimentin for rheumatoid arthritis. Clin Exp Rheumatol 29(1):85–88PubMed
37.
Zurück zum Zitat Dejaco C, Klotz W, Larcher H et al (2006) Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis. Arthritis Res Ther 8(4):R119PubMedCentralCrossRefPubMed Dejaco C, Klotz W, Larcher H et al (2006) Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis. Arthritis Res Ther 8(4):R119PubMedCentralCrossRefPubMed
38.
Zurück zum Zitat Ursum J, Nielen MM, Schaardenburg DV et al (2008) Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther 10(1):R12PubMedCentralCrossRefPubMed Ursum J, Nielen MM, Schaardenburg DV et al (2008) Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study. Arthritis Res Ther 10(1):R12PubMedCentralCrossRefPubMed
39.
Zurück zum Zitat Wagner E, Skoumal M, Bayer P, Klaushofer K (2009) Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis. Rheumatol Int 29(11):1315–1321CrossRefPubMed Wagner E, Skoumal M, Bayer P, Klaushofer K (2009) Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis. Rheumatol Int 29(11):1315–1321CrossRefPubMed
40.
Zurück zum Zitat Yousefghahari B, Alhooei S, Soleimani-amiri MJ, Guran A (2013) Comparison of sensitivity and specificity of anti-CCP and anti-MCV antibodies in an Iranian cohort of patients with rheumatoid arthritis. Caspian J Intern Med 4(3):702PubMedCentralPubMed Yousefghahari B, Alhooei S, Soleimani-amiri MJ, Guran A (2013) Comparison of sensitivity and specificity of anti-CCP and anti-MCV antibodies in an Iranian cohort of patients with rheumatoid arthritis. Caspian J Intern Med 4(3):702PubMedCentralPubMed
41.
Zurück zum Zitat Maraina CHC, Nurdayana AK, Rusni D, Azwany Y (2010) Diagnostic value of anti‐modified citrullinated vimentin in rheumatoid arthritis. Int J Rheum Dis 13(4):335–339CrossRefPubMed Maraina CHC, Nurdayana AK, Rusni D, Azwany Y (2010) Diagnostic value of anti‐modified citrullinated vimentin in rheumatoid arthritis. Int J Rheum Dis 13(4):335–339CrossRefPubMed
42.
Zurück zum Zitat Bartoloni E, Alunno A, Bistoni O et al (2012) Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: an Italian multicentric study and review of the literature. Autoimmun Rev 11(11):815–820CrossRefPubMed Bartoloni E, Alunno A, Bistoni O et al (2012) Diagnostic value of anti-mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: an Italian multicentric study and review of the literature. Autoimmun Rev 11(11):815–820CrossRefPubMed
Metadaten
Titel
Diagnostic accuracy of anti-MCV and anti-CCP antibodies in rheumatoid arthritis
A meta-analysis
verfasst von
Y.H. Lee, MD, PhD
S.-C. Bae
G.G. Song
Publikationsdatum
01.12.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Zeitschrift für Rheumatologie / Ausgabe 10/2015
Print ISSN: 0340-1855
Elektronische ISSN: 1435-1250
DOI
https://doi.org/10.1007/s00393-015-1598-x

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