160 likes | 364 Views
Use of biomarkers in clinical diagnosis and prognosis of RA. Dr Eugen Feist Department of Rheumatology and Clinical Immunology Charité – Universitätsmedizin, Berlin, Germany. Goal: Early diagnosis and stratification . Clinical Examination. Novel Markers. Improved Imaging. Ubiquitous. ACPA.
E N D
Use of biomarkers in clinical diagnosis and prognosis of RA Dr Eugen Feist Department of Rheumatology and Clinical Immunology Charité – Universitätsmedizin, Berlin, Germany
Goal: Early diagnosis and stratification Clinical Examination Novel Markers Improved Imaging Ubiquitous ACPA Profiling Nienhuis et al., ARD 1964; Young et al., Br Med. J 1979; Schellekens et al., JCI 1998
Anti-CCP antibodies precede disease onset Half of patients were IgM-RF and/or anti-CCP+ 4.5 years (median) before the onset of disease (0.1–13.8 years) 50 IgM-RF Anti-CCP IgM-RF or anti-CCP 40 30 Sensitivity (percentage positivity) 20 10 0 Nielen et al. Arthritis Rheum 2004;50:380-86 Anti-CCP, anti-cyclic citrullinated peptide
Half of patients with undifferentiated arthritis develop confirmed RA at 1 year Avouac et al. Ann Rheum Dis 2006;65:845–851
Structural comparison of CCP and mutated citrullinated vimentin (MCV) CCP synthetic peptides of app. 20 AA (1 - 2 potential epitopes) Human Vimentin = recombinant protein of 54 kD and app. 45 arginins = modified by enzymatic deimination and mutation e.g.: STRSVSSSSYXXMFR TYSLGSALRPSTSXSLYASSPXR GPGTASRPSSSR X: Citrullination (Arg-->Citr) R: g/c-Transversion (Gly-->Arg) X: g/c-Transversion (Gly-->Arg) and citrullination (Arg-->Citr) G,T: New tryptic cleavage site caused by g/c-Transversion Bang et al., Arthritis Rheum 2007
Comparison of autoantibodies against citrullinated antigens Bang et al., Arthritis Rheum 2007
273 patients with early RA Anti-MCV Sensitivity = 70.7% Specificity = 95% Anti-CCP Sensitivity = 57.9% Specificity = 96% Anti-MCV predictive for high disease activity “Anti-MCV in early RA: Higher sensitivity and extended prognostic value” anti-MCV+ anti-MCV- 10 7.5 ** SJC 5 *** ** *** **p< 0.01; *** p < 0.001 *** 2.5 0 0 3 months 1 year 2 years 3 years 5 years Mathsson et al., Arthritis Rheum 2008
“Anti-MCV in early RA: Higher sensitivity and extended prognostic value” anti-MCV+ anti-MCV- TJC DAS28 10 8 6 6 5 4 4 * ** * * 3 2 2 0 1 0 3 months 1 year 2 years 3 years 5 years 0 3 months 1 year 2 years 3 years 5 years *P < 0.05; **P < 0.01 Mathsson et al. Arthritis Rheum 2008;58(1):36–45.
Anti-MCV appears to perform better than anti-CCP in identifying poor radiological prognosis in early RA *Mann-Whitney U test Mathsson et al., Arthritis Rheum 2008
Decrease in anti-CCP titres reported to be associated with treatment efficacy Evolution of anti-CCP titres in adalimumab-treated patients NS NS P=0.001 ND Anti-CCP titre Atzeni, et al. Arthritis Res Ther. 2006;8(1):R3.
Analytic precision and diagnostic performance of different anti-CCP assays Bizzaro et al., Clin Chem 2007
Novel rapid point of care tests Comparison of CCPoint® and standard CCP2-ELISA in 109 RA, 351 non-RA, 420 HD CCPoint® test was fast, valid and reliable (sensitivity & specificity 95%) Comparison of RheumaChec® and standard MCV-ELISA in 80 RA, 83 non-RA and 200 HD Sensitivity of MCV+ patients in whole blood 70.2% (serum 94.7%) and specificity 98.9% Snijders GF et al., Scand J Rheumatol 2008
Autoantibodies as prognostic markers in RA RF CCP/MCV App. 70% Erosive manifestation Seropositive App. 30% Seronegative Mild manifestation
Summary Anti-CCP antibodies precede RA occurrence Citrullination modifies potential autoantigens and likely plays an important role in the pathogenesis of RA Detection of anti-CCP significantly improves the diagnosis of early RA Anti-CCP and anti-MCV immunoassays provide a comparable diagnostic sensitivity and specificity
What does this mean for Ed’s patient? Anti-CCP provides a high diagnostic probability in an RF-negative patient with undifferentiated arthritis