anti-MCV Levels Research Articles

Unique Correlation Between Mutated Citrullinated Vimentine IgG Autoantibodies and Markers of Systemic Inflammation in Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is the most common inflammatory systemic autoimmune disease, primarily affecting the peripheral joints. Anti-mutated citrullinated vimentin autoantibodies (anti-MCV) of IgG isotype were shown to be a useful diagnostic marker of RA especially in RA patients who were anti-cyclic citrullinated protein autoantibodies (anti-CCP) negative. Nevertheless, published data correlates rheumatoid factor (RF), anti-CCP or anti-MCV antibodies with either erythrocyte sedimentation rate (ESR) or serum C-reactive protein (CRP) as markers of disease activity, not investigated the possible correlations of RA autoantibodies towards ESR and CRP in comparison. Herein, we aim to evaluate the usefulness of anti-MCV as a dependable marker in established RA compared with anti-CCP and RF antibodies and to examine correlations between RF, anti-CCP and anti-MCV antibodies towards ESR and serum CRP. Serum RF-IgA, RF-IgM, anti-CCP and anti-MCV levels were measured in 30 patients with RA and 40 patients with other autoimmune diseases (non-RA) compared with 20 normal subjects. Specificity, sensitivity and AUC for RF antibodies, anti-CCP and anti-MCV were calculated towards RA diagnosis. Our results showed that ESR and CRP had significantly higher values in both RA and non-RA patients compared with our healthy controls with observed significant increment in RA patients compared with non-RA patients. An important finding from our study is that 33.3% of RA patients were anti-CCP negative but being positive towards anti-MCV. Also, in-between 36.7 up to 40% of RA patients were RF-IgA and RF-IgM negative while being anti-MCV positive. Anti-MCV antibodies showed the highest specificity and sensitivity (97.5 and 86.6%, respectively) towards RA diagnosis with the highest AUC value (0.920) compared with anti-CCP and RF antibodies. Correlation analyses revealed that there was no significant correlation between ESR along with CRP towards RF-IgA, RF-IgM and anti-CCP while profound highly significant correlation exhibited between ESR and CRP towards anti-MCV data (r=0.879 and 0.994, respectively). Thus, our data suggest that the assessment of serum anti-MCV autoantibodies along with ESR and CRP considered as a simple laboratory regime for monitoring RA patients to assess and follow-up disease activity. The addition of anti-MCV autoantibodies to serologic markers in the ACR/EULAR classification criteria for RA will add points for patients with negative anti-CCP and RF antibodies.

The diagnostic and monitoring value of serum anti-mutated citrullinated vimentin antibodies (anti-MCV) in juvenile rheumatoid arthritis

Background: JRA is currently diagnosed using the American College of Rheumatology (ACR) 1987 revised criteria that are primarily based on clinical parameters. The criteria may be insufficient for the diagnosis of early RA as they are based upon measurements of disease classification predominately featuring manifestations typical of later-stage disease. Measurement of serum anti-mutated citrullinated vimentin antibodies (MCV) has been shown to be a better marker for early adult RA, and it correlates well with the disease activity score (DAS). Objectives: The aim of this work is to evaluate the role of antimutated citrullinated vimentin antibodies (anti-MCV) in the diagnosis, and in monitoring disease activity in juvenile rheumatoid arthritis. Methods: The study included 40 children with JRA fulfilling the American College of Rheumatology criteria for diagnosis of JRA: 4 children with oligoarticular JRA, 12 with polyarticular JRA and 24 children with systemic onset JRA. Fifty healthy children, matching the patients in age and sex served as a control group. The studied children with JRA were subjected to laboratory tests including CBC, ESR, CRP, ANA and rheumatoid factor (RF). Serum samples from both patients and controls were assayed for anti-MCV levels using an ELISA technique. Results: The study showed high mean serum anti-MCV antibodies level in JRA patients when compared to controls (P= 0.00). In addition, there were no significant correlations between anti-MCV antibody levels and parameters of disease activity, namely, number of swollen joints, number of tender joints, ESR and CRP. The receiver operating characteristic (ROC) curve was drawn and it showed that the area under the curve (AUC) was (0.896). At a cutoff level > 17 u/mL, anti-MCV antibodies had diagnostic specificity of 88%, diagnostic sensitivity of 87.5%, negative and positive predictive values of 89.8% and 85.4%, respectively and diagnostic efficacy of 87.8%. We also reported 3/40 of JRA patients to be positive for RF and 2/40 of JRA patients to be positive for ANA. Conclusion: Measurement of serum anti MCV antibody level holds promise as a diagnostic tool in JRA. However, they failed to show a significant efficacy in determining disease activity. Keywords: Juvenile rheumatoid arthritis, MCV Egypt J Pediatr Allergy Immunol 2012;10(2):75-80

Antibodies to mutated citrullinated vimentin in patients with chronic hepatitis C Virus genotype IV infection-related arthropathy

One of the extra-hepatic manifestations of hepatitis C virus (HCV) infection is polyarthritis that mimics rheumatoid arthritis (RA). Anti-mutated citrullinated vimentin (MCV) was recently introduced in the diagnostic workup of RA, but its exact role in HCV infection and its related arthropathy is still unclear. The aim of the study is to determine the prevalence of anti-MCV antibodies in HCV-infected patients with or without articular involvement, and to investigate whether anti-MCV antibodies have an additional role to anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) in differentiating patients with RA from patients with HCV-related arthropathy. Fifty-five HCV-infected patients (HCV RNA positive) and 30 RA patients (fulfilling the American College of Rheumatology classification criteria for RA and negative for HCV) were included. Anti-MCV antibodies, anti-CCP antibodies, RF and cryoglobulins were measured. Articular involvement in hepatitis C patients was evaluated. Articular involvement was detected in 30/55 (54.5%) of HCV-infected patients. The most frequent pattern was symmetric polyarthralgias and the most frequent joints to be involved were the wrists, metacarpophalangeal joints, shoulders and knees. In HCV arthropathy, anti-MCV was positive in 9/30 (30%), anti-CCP in 0% and RF in 22/30 (73.3%). Whereas, in chronic HCV without arthropathy, anti-MCV was positive in 8 patients (32%), anti-CCP in one patient (4%) and RF in 23/25 (92.0%). There was no significant difference between the two HCV groups as regards the frequencies of anti-MCV (P = 0.89), anti-CCP (P = 0.93) and RF (P = 0.15). In RA, anti-MCV was positive in 93.3% anti-CCP in 96.7% and RF in 86.7%. There was no significant difference in RF between RA and HCV arthropathy (P = 0.33). Meanwhile, there was a highly significant difference between both groups regarding anti-MCV and anti-CCP (P < 0.0001 for each). The sensitivity of anti-MCV, anti-CCP and RF for RA was 93.3, 96.7 and 86.7%, respectively. Whereas their specificity was 69.1, 98.2 and 18.2%, respectively. In addition, the mean levels of anti-MCV and anti-CCP were significantly increased in RA than in all HCV patients (P = 0.038 and P < 0.0001, respectively). Meanwhile, there were no significant differences in mean levels of anti-MCV and anti-CCP between HCV patients with arthropathy and those without arthropathy (P = 0.11 and P = 0.73, respectively). Also, there were no differences in mean RF between both HCV groups. There was a significant positive correlation between anti-MCV and anti-CCP levels in patients with HCV-related arthropathy (r = 0.39, P = 0.032) and in those without arthropathy (r = 0.578, P = 0.002). Cryoglobulins were detected in 7/30 HCV-related arthropathy (23.3%) and were positively correlated with anti-MCV(r = 0.485, P = 0.007). Anti-CCP still attains the major role in differentiating RA from HCV arthropathy. Anti-MCV seems to play no additional role in this aspect. The role of mutation of vimentin in the pathogenesis of HCV arthropathy is not as clear as it is for RA and needs further investigation.

PADI4 polymorphisms and related haplotype in rheumatoid arthritis patients

ObjectiveTo investigate whether peptidyl arginine deiminase type IV gene (PADI4) polymorphisms contribute to rheumatoid arthritis (RA) susceptibility in Egyptians, whether they influence disease severity and activity, and whether they affect anti-mutated citrullinated vimentin antibodies (anti-MCV) level. MethodsThree PADI4 single nucleotide polymorphisms (SNPs) (PADI4-92, PADI4-96, and PADI4-102) were screened in 275 RA patients and 275 unaffected controls by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. Serum anti-MCV levels were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThere were significant associations between RA susceptibility with the minor alleles of PADI4-92 and PADI4-102 [odds ratio (OD) and 95% confidence interval (CI) for the minor alleles of PADI4-92 and PADI4-102: 1.48 (1.17–1.88) and 2.05 (1.61–2.61) respectively] but not with PADI4-96 [OD and 95% CI for the C allele: 1.09 (0.86–1.39)]. PADI4 haplotypes 2 (GCC) and 3 (GCT) were also associated with RA susceptibility while PADI4 haplotypes 1 (CTC) may be protective against developing of this disease. A significant association was detected between PADI4 haplotypes and RA severity. ConclusionsThe PADI4 SNPs and haplotypes were associated with RA susceptibility, although no relation was observed between the PADI4 haplotypes and anti-MCV levels.

Anti-mutated citrullinated vimentin (anti-MCV) and anti-65 kDa heat shock protein (anti-hsp65): New biomarkers in ankylosing spondylitis

Introduction Citrullination as well as anti-citrullinated protein/peptide antibodies (ACPA) have been implicated in the pathogenesis of rheumatoid arthritis (RA). While ACPAs are specific and sensitive markers for RA, there have been hardly any reports regarding ACPAs in ankylosing spondylitis (AS). The possible role of antibodies to Mycobacterial 65 kDa heat shock protein (hsp65) has not been characterized in AS. As new laboratory biomarkers of AS are needed, we investigated the prevalence of anti-mutated citrullinated vimentin (MCV) and anti-hsp65 antibodies in AS. Methods Altogether 43 AS and 44 healthy controls were included in the study. Anti-MCV and anti-hsp65 were determined in sera by commercial and in-house ELISA, respectively. Serum autoantibody levels were correlated with ESR, CRP, HLA-B27 status, smoking habits, pain intensity, BASDAI, BASFI and BASMI indices. Results Patients with AS had significantly higher serum anti-MCV levels (17.3 U/mL, range: 8.3–31.5 U/mL) in comparison to healthy subjects (8.9 U/mL, range: 5.4–13.3 U/mL) ( p < 0.01). Sixteen of the 43 AS patients (37%) and none of the 44 healthy controls (0%) were anti-MCV positive using the cut-off value recommended by the manufacturer (> 20 U/mL). The mean anti-hsp65 concentration in AS sera was 124.8 AU/mL (range: 27.2–1000 AU/mL), while controls exerted significantly lower anti-hsp65 levels (mean: 51.8 AU/mL; range: 22.5–88.5 AU/mL) ( p < 0.001). Correlation analysis revealed that both anti-MCV positivity ( r = 0.613; p = 0.012) and absolute serum anti-MCV levels ( r = 0.553; p = 0.021) correlated with anti-hsp65 levels. Anti-MCV positivity also correlated with ESR ( r = 0.437; p = 0.03). Conclusions Anti-MCV and anti-hsp65 may be novel biomarkers in AS.

Association of Anti-Modified Citrullinated Vimentin with Subclinical Atherosclerosis in Early Rheumatoid Arthritis Compared with Anti-Cyclic Citrullinated Peptide

To investigate anti-modified citrullinated vimentin (anti-MCV) in early rheumatoid arthritis (RA), including correlation with disease activity and cardiovascular risk factors, compared with anti-cyclic citrullinated peptides (anti-CCP3). Anti-MCV and anti-CCP3 concentrations were measured in 100 patients with early RA and 100 healthy controls at baseline to determine sensitivity and specificity. Patients received methotrexate (MTX) 0.2 mg/kg/week plus prednisone 10 mg/day. Anti-MCV, anti-CCP3, rheumatoid factor (RF), Disease Activity Score for 28 joints (DAS-28), lipid profile, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein assay (hsCRP), homeostasis model assessment for insulin resistance (HOMA-IR) index, tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and carotid intima-media thickness (cIMT) were measured before and after 12 months of treatment. The sensitivity and specificity for anti-MCV antibody were 75% and 90%, respectively, and for anti-CCP3 antibody 71% and 96%. Serum anti-MCV and serum anti-CCP3 levels at baseline were positively correlated with hsCRP, IL-6, HOMA-IR index, serum RF levels (p < 0.001), and cIMT (p < 0.05). Serum anti-MCV was positively correlated with serum anti-CCP3 levels. There were significant positive correlations between the percentage of changes of anti-MCV levels versus changes in DAS-28, ESR, hsCRP, atherogenic ratios (TC/HDL-C and LDL-C/HDL-C), apolipoprotein A-I, IL-6, TNF-α, HOMA-IR index, and cIMT. These correlations were not found between changes in anti-CCP3 levels compared to clinical, laboratory, and radiological variables. Anti-MCV was as sensitive as anti-CCP3 in diagnosing early RA. Anti-MCV testing appears to be useful for monitoring associated subclinical atherosclerosis in early RA.

Antibodies targeting mutated citrullinated vimentin in patients with psoriatic arthritis

Antibodies against mutated citrullinated vimentin (anti-MCV) are of a comparable diagnostic value in rheumatoid arthritis (RA) as antibodies targeting citrullinated peptides (anti-CCP). Anti-CCP are present in up to 15% of psoriatic arthritis (PsA) patients, while the prevalence of anti-MCV in PsA patients has been poorly investigated. The aim of the present study was to assess the prevalence and relevance of anti-MCV antibodies in PsA patients. The study included 56 PsA patients. Clinical features, disease activity, and functional ability were noted by an experienced rheumatologist. Serum samples of all patients were analyzed for anti-MCV and anti-CCP antibodies using enzyme-linked immunosorbent assay. Data on 92 patients with RA, 44 patients with other inflammatory rheumatic diseases, and 107 healthy controls from a previous study were used to compare the prevalence of anti-MCV antibodies in PsA patients. Anti-MCV antibodies were positive in only two out of 56 (3.6%) PsA patients, which was significantly lower compared to RA patients (63%). The anti-MCV level was moderately positive and borderline in one patient each. Both patients had asymmetric polyarthritis, dactylitis, moderate to high disease activity, and were anti-CCP and rheumatoid factor (RF) negative. There was no significant difference in anti-MCV levels according to clinical subtypes of PsA and no correlation of anti-MCV levels with anti-CCP, RF, disease activity variables, and functional ability indices. According to study results, anti-MCV antibodies can be detected in a very small proportion of PsA patients with polyarthritic disease and are primarily related to the polyarthritic pattern rather than the specific diagnosis of RA.

Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study

Objectives:Anti-citrullinated peptide antibodies (ACPAs) are established as useful predictors of radiographic progression in rheumatoid arthritis (RA). The main objective of this study was to test the prognostic capacity of the...

Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis

The aim of this study was to determine the performance of antibodies against mutated citrullinated vimentin (anti-MCV) in comparison with antibodies to cyclic citrullinated peptides (anti-CCP) in patients with rheumatoid arthritis (RA). Serum levels of anti-MCV and anti-CCP were determined in 193 patients with RA and 332 controls, and sensitivity and specificity were calculated. In a separate analysis of 86 patients, the anti-MCV levels were compared to disease activity. Sensitivity of anti-MCV versus anti-CCP was 71.5 and 69.4%, specificity was 81.3 and 97.6%, respectively. The ROC curves showed higher specificity and an advantage of anti-CCP. In seronegative RA patients the sensitivity of anti-MCV was superior over anti-CCP. Anti-MCV positivities also occurred in systemic lupus erythematosus and Sjoegren's syndrome. In a subgroup of 86 RA patients we found a significant correlation between anti-MCV and disease activity. Anti-MCV appears to be an important marker for the diagnosis of RA, and correlates also with disease activity.

THE INFLUENCE OF ADIPOKINES ON BONE MINERAL DENSITY IN ELDERLY MEN

disease duration; 10.25±4.61 years), and 19 healthy subjects (mean age; 40.26±5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. Results: In all RA patients, mean antiCCP level was 69.07±90.43 U/ml and anti-MCV level was 665.77±1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7±5.22 U/ml and anti-MCV level was 40.54±20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11±7.65 U/ml, anti-MCV level was 23.12±12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54±98.07 U/ml and anti-MCV level was 998.74±1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77±1.55 U/ml and anti-MCV level was 27.59±23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and antiCCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and healthy controls patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). Conclusion: As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.

DIAGNOSTIC UTILITY OF ANTI-CYCLIC CITRULLINATED PEPTIDE AND ANTI-MODIFIED CITRULLINATED VIMENTIN ANTIBODIES IN RHEUMATOID ARTHRITIS

Several autoantibodies found in RA are directed to epitopes in citrullinated proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We tested the value a newly developed ELISA for the detection of antibodies againts a genetically modified citrullinated vimentin (anti-MCV) in comparison with an anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA (mean age; 42.6 ± 10.87 years, mean disease duration; 9.37 ± 3.98 years) were enrolled in this study. Twenty – five ankylosing spondylitis (mean age; 35.88 ± 6.64 years, mean disease duration; 10.25 ± 4.61 years), and 19 healthy subjects (mean age; 40.26 ± 5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP level was 69.07 ± 90.43 U/ml and anti-MCV level was 665.77 ± 1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7 ± 5.22 U/ml and anti-MCV level was 40.54 ± 20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11 ± 7.65 U/ml, anti-MCV level was 23.12 ± 12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54 ± 98.07 U/ml and anti-MCV level was 998.74 ± 1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77 ± 1.55 U/ml and anti-MCV level was 27.59 ± 23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and anti- CCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.

Diagnostic Utility of Anti-Cyclic Citrullinated Peptide and Anti-Modified Citrullinated Vimentin Antibodies in Rheumatoid Arthritis

Several autoantibodies found in RA are directed to epitopes in citrullinated proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We tested the value a newly developed ELISA for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with an anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA (mean age; 42.6 +/- 10.87 years, mean disease duration; 9.37 +/- 3.98 years) were enrolled in this study. Twenty -five ankylosing spondylitis (mean age; 35.88 +/- 6.64 years, mean disease duration; 10.25 +/- 4.61 years), and 19 healthy subjects (mean age; 40.26 +/- 5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP level was 69.07 +/- 90.43 U/ml and anti-MCV level was 665.77 +/- 1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7 +/- 5.22 U/ml and anti-MCV level was 40.54 +/- 20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11 +/- 7.65 U/ml, anti-MCV level was 23.12 +/- 12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54 +/- 98.07 U/ml and anti-MCV level was 998.74 +/- 1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77 +/- 1.55 U/ml and anti-MCV level was 27.59 +/- 23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and anti- CCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.

Antibodies to mutated citrullinated vimentin and disease activity score in early arthritis: a cohort study

IntroductionThe aim of our study was to investigate the association between arthritic disease activity and antibodies to mutated citrullinated vimentin (anti-MCV), because such a relation has been suggested.MethodsAnti-MCV levels were measured in 162 patients with early arthritis (123 with rheumatoid arthritis and 39 with undifferentiated arthritis) at baseline and at 1 and 2 years of follow up. Disease activity was measured using the disease activity score (Disease Activity Score based on 28 joints [DAS28]) and serum C-reactive protein. General estimation equation analysis was used to assess the relation between anti-MCV levels and DAS28 over time.ResultsBoth, anti-MCV levels and DAS28 exhibited a significant decrease during the first and second year. However, the association between anti-MCV levels and DAS28, adjusted for dependency on sequential measurements within one individual, was very low (β = 0.00075). In a population of patients with rheumatoid arthritis or undifferentiated arthritis, anti-MCV had a specificity of 92.3% and a sensitivity of 59.3% when using the recommended cut-off of 20 U/ml. Specificity and sensitivity of antibodies against second-generation cyclic citrullinated peptide, using the recommended cut-off value of 25 U/ml, were 92.1% and 55.3%, respectively. Anti-MCV-positive early arthritis patients had significantly higher Sharp-van der Heijde score, erythrocyte sedimentation rate and C-reactive protein levels than did anti-MCV-negative patients at all time points (P < 0.005), but DAS28 was higher in anti-MCV-positive patients at 2 years of follow up only (P < 0.05).ConclusionBecause the correlation between anti-MCV levels and parameters of disease activity was very low, we conclude that it is not useful to monitor disease activity with anti-MCV levels.

Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy

IntroductionAntibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA.MethodsWe studied two groups of RA patients, one with (n = 80) and one without (n = 76) anti-CCP antibodies. The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases (51 psoriatic rheumatism, 58 primary Sjögren syndrome, and 49 ankylosis spondylitis). Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6, 12, 18, and 24 months of infliximab treatment. Anti-CCP2 and anti-MCV levels were assayed using a commercial enzyme-linked immunosorbent assay. IgM rheumatoid factor was determined by nephelometry.ResultsIn accordance with the cutoff values recommended by the manufacturer, the specificity of anti-MCV antibodies was 90.9%. We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies (94.2%). With this optimal cutoff, anti-MCV antibodies were found in 11.8% (9/76) of RA patients without anti-CCP, and similarly, anti-CCP antibodies were found in 11.2% (9/80) of RA patients without anti-MCV. Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor. Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline (P < 0.01) as a significant decrease of anti-CCP levels occurred only at 24 months (P < 0.04). Moreover, an anti-MCV decrease was significantly associated with DAS28 (disease activity score using 28 joint counts) improvements 12 months into therapy.ConclusionsOur results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV. Moreover, anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy.

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

The Sa autoantigen can be found in inflamed synovium of patients with rheumatoid arthritis (RA), and at least part of the humoral RA-specific anti-Sa response is directed against citrullinated vimentin. This study was undertaken to evaluate the sensitivity, specificity, and prognostic value of determination of levels of antibodies against modified citrullinated vimentin (anti-MCV) as compared with antibodies against cyclic citrullinated peptides (anti-CCP) in an inception cohort of patients with early RA. Clinical data, radiographs, and measurements of levels of anti-MCV and anti-CCP antibodies were obtained in 273 patients with early RA at baseline, after 3 months, and after 1, 2, 3, and 5 years. Autoantibodies were also analyzed in 100 healthy controls. Of the 273 patients, 193 (70.7%) were anti-MCV positive and 158 (57.9%) were anti-CCP positive at the time of diagnosis, with nearly equal specificities (95% and 96%, respectively). Forty (14.7%) were anti-MCV positive only, and 5 (1.8%) were anti-CCP positive only. Anti-MCV-positive and anti-MCV-negative patients had similar disease activity at baseline, but presence of anti-MCV was predictive of subsequent high disease activity and continued radiographic progression. Changes in anti-MCV level showed stronger correlation with changes in clinical parameters than did changes in anti-CCP level. The subgroup of patients who were anti-MCV positive and anti-CCP negative showed a higher rate of radiographic destruction than did patients who were negative for both anti-MCV and anti-CCP. These findings show that when patients with early RA are compared with healthy controls, analysis of anti-MCV yields greater sensitivity and unchanged specificity as compared with analysis of anti-CCP. Anti-MCV also appears to perform better than anti-CCP in identifying poor radiographic prognosis in patients with early RA.