Background: The inability to accurately predict the development of RA in a proportion of patients with early UA means that there is a need to assess the utility of novel biomarkers, other than the positivity of autoantibodies, to be introduced in predictive algorithms. Objectives: To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of early rheumatoid arthritis (ERA). Methods: Anti-CCP2 and Anti-MCV antibodies, IgM and IgA RF, Reuma Test, IL-6 by ELISA and ESR and CRP in serum samples from 185 ERA patients and 158 control subjects (106 with undifferentiated arthritis (UA) and 52 healthy controls) were tested. ROC curves were constructed. To determine the added diagnostic value of testing RF isotypes and inflammatory biomarkers in addition to anti-CCP and anti-MCV, as oppose to ACPA testing alone, a parallel test by combining two tests (at least one of both positive) was used. Differences were evaluated with McNemar test. Results: Sensitivity for ERA, at 95% specificity, was highest for the anti-CCP2(70.3%) and anti-MCV(65.2%), followed by RF-IgM(40.5%), IL-6(29.2%), RF-IgA(29.7%), ESR(20.6%) and CRP(16.1%). Inter-test differences in sensitivities were not significant between anti-CCP2 and anti-MCV (p=0.08), and both were significantly better than IL-6, RF-IgM and RF-IgA (p<0.001).Using the parallel approach, the combination of anti-CCP2 antibodies and anti-MCV gave a sensitivity of 74.6% and a specificity of 89.2%. The marker combination of anti-CCP2 and IL-6 resulted in a significantly sensitivity gain of 9.7% (p<0.001) and a minor, but significantly (p=0.01), lack in specificity of 5.8% compared with anti-CCP as a single marker. Sensitivity was also significantly higher for the combination of anti-MCV and IL-6 compared with anti-MCV as a single bio-marker (sensitivity gain:8.2%, p<0.001), but specificity is reduced to 88.6% (p=0.01). When other marker combinations along with anti-CCP2 were considered, sensitivity for ERA ranged from 73.5%(RF-IgM) to 73.0%(RF-IgA), with a loss in specificity which ranges from 89.9% for RF-IgA to 89.2% for RF-IgM, respectively. When the other marker combinations along with anti-MCV were considered, sensitivity for ERA ranged from 70.3% (RF-IgA) to 71.2% (RF-IgM). The inter-test differences in sensitivities were significant between the combination of anti-CCP2+IL6 vs anti-CCP2+RF-IgM (p=0.01) or anti-CCP+RF-IgA (p=0.006). In none of these cases the differences in specificity were significant. Considering the cut-off suggested by the manufacturers for the autoantibodies positivity, 18.9% of ERA patients were negative for a-MCV/a-CCP/RFIgA/RFIgM compared to 69.8% (p<0.001) of UA and 84.6%(p<0.001) of controls. Moreover, adding the IL6 evaluation (cut-off: 16.1pg/ml) in the panel, 15.7% of ERA patients were negative for the combination of a-MCV/a-CCP/IL6, compared to 78.3% (<0.001) in UA patients and 84.6% (<0.001) in controls. Conclusion: Our data showed that anti-CCP and anti-MCV are better than other laboratory tests in sensitivity and specificity as diagnostic biomarkers. The inflammation marker IL-6 in support of anti-CCP or anti-MCV has the highest classification power for the diagnosis of ERA.
ACPA–IL-6 as the best biomarkers to differentiate early rheumatoid arthritis from undifferentiated arthritis: analysis of the diagnostic performance
Gremese E;
2010-01-01
Abstract
Background: The inability to accurately predict the development of RA in a proportion of patients with early UA means that there is a need to assess the utility of novel biomarkers, other than the positivity of autoantibodies, to be introduced in predictive algorithms. Objectives: To test if a combination of biomarkers can increase the classification power of autoantibodies to cyclic citrullinated peptides (anti-CCP) in the diagnosis of early rheumatoid arthritis (ERA). Methods: Anti-CCP2 and Anti-MCV antibodies, IgM and IgA RF, Reuma Test, IL-6 by ELISA and ESR and CRP in serum samples from 185 ERA patients and 158 control subjects (106 with undifferentiated arthritis (UA) and 52 healthy controls) were tested. ROC curves were constructed. To determine the added diagnostic value of testing RF isotypes and inflammatory biomarkers in addition to anti-CCP and anti-MCV, as oppose to ACPA testing alone, a parallel test by combining two tests (at least one of both positive) was used. Differences were evaluated with McNemar test. Results: Sensitivity for ERA, at 95% specificity, was highest for the anti-CCP2(70.3%) and anti-MCV(65.2%), followed by RF-IgM(40.5%), IL-6(29.2%), RF-IgA(29.7%), ESR(20.6%) and CRP(16.1%). Inter-test differences in sensitivities were not significant between anti-CCP2 and anti-MCV (p=0.08), and both were significantly better than IL-6, RF-IgM and RF-IgA (p<0.001).Using the parallel approach, the combination of anti-CCP2 antibodies and anti-MCV gave a sensitivity of 74.6% and a specificity of 89.2%. The marker combination of anti-CCP2 and IL-6 resulted in a significantly sensitivity gain of 9.7% (p<0.001) and a minor, but significantly (p=0.01), lack in specificity of 5.8% compared with anti-CCP as a single marker. Sensitivity was also significantly higher for the combination of anti-MCV and IL-6 compared with anti-MCV as a single bio-marker (sensitivity gain:8.2%, p<0.001), but specificity is reduced to 88.6% (p=0.01). When other marker combinations along with anti-CCP2 were considered, sensitivity for ERA ranged from 73.5%(RF-IgM) to 73.0%(RF-IgA), with a loss in specificity which ranges from 89.9% for RF-IgA to 89.2% for RF-IgM, respectively. When the other marker combinations along with anti-MCV were considered, sensitivity for ERA ranged from 70.3% (RF-IgA) to 71.2% (RF-IgM). The inter-test differences in sensitivities were significant between the combination of anti-CCP2+IL6 vs anti-CCP2+RF-IgM (p=0.01) or anti-CCP+RF-IgA (p=0.006). In none of these cases the differences in specificity were significant. Considering the cut-off suggested by the manufacturers for the autoantibodies positivity, 18.9% of ERA patients were negative for a-MCV/a-CCP/RFIgA/RFIgM compared to 69.8% (p<0.001) of UA and 84.6%(p<0.001) of controls. Moreover, adding the IL6 evaluation (cut-off: 16.1pg/ml) in the panel, 15.7% of ERA patients were negative for the combination of a-MCV/a-CCP/IL6, compared to 78.3% (<0.001) in UA patients and 84.6% (<0.001) in controls. Conclusion: Our data showed that anti-CCP and anti-MCV are better than other laboratory tests in sensitivity and specificity as diagnostic biomarkers. The inflammation marker IL-6 in support of anti-CCP or anti-MCV has the highest classification power for the diagnosis of ERA.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
