Rheumatoid Arthritis: Nicaise-Roland P

Grootenboer-Mignot S, Nicaise-Roland P, Delaunay C, Meyer O, Chollet-Martin S, Labarre C. · Laboratory of Immunology, AP-HP Bichat-Cl, Bernard Hospital, 75877 Paris, France. · Scand J Rheumatol. · Pubmed #15370715 No free full text.

Abstract: We compared the diagnostic performance of anti-cyclic citrullinated peptide antibodies detected with second-generation enzyme immunoassay (anti-CCP2) with that of IgM-rheumatoid factor (RF), anti-perinuclear factor (APF), and anti-keratin antibodies (AKA). The sensitivity of anti-CCP2 was better than that of APF and AKA: they were detected in 25% rheumatoid arthritis (RA) patients without detectable APF or AKA. Their specificity, evaluated in other inflammatory rheumatic disease, was similar to that of APF and AKA. Despite the lower specificity, IgM-RF in combination with anti-CCP2 is interesting, as they do not completely overlap. Anti-CCP2 antibody detection seems to be a good alternative to other anti-filaggrin antibodies in the diagnosis of RA.

Bruns A, Nicaise-Roland P, Hayem G, Palazzo E, Dieudé P, Grootenboer-Mignot S, Chollet-Martin S, Meyer O. · Rheumatology Department, Bichat Teaching Hospital, AP-HP, CHU Bichat, 46 rue Henri Huchard, 75018 Paris, France. · Joint Bone Spine. · Pubmed #19208451 No free full text.

Abstract: BACKGROUND: Antibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNFalpha antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP titres to a treatment response (defined as a good or moderate EULAR response) after 48 weeks of infliximab therapy. METHODS: Thirty-six patients with long-standing RA not responding to disease-modifying anti-rheumatic drugs (DMARDs) received intravenous infliximab (starting dose: 3mg/kg) at 0, 2, and 6 weeks then at 8-week intervals, in combination with a DMARD. At baseline, week 24, and week 48, C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were determined and the disease activity score (DAS28) was calculated. Serum samples collected at the same time points were used to measure anti-CCP (commercial second-generation ELISA), IgM-RF (quantitative nephelometric assay), and ANA (indirect immunofluorescence in HEp2 cells). Correlations linking baseline autoantibody titres to changes in autoantibody levels were examined. RESULTS: At baseline, tests were positive for anti-CCP in 31/36 (94.6%) patients, IgM-RF in 29/36 (80.5%) patients, and ANA in 16/36 (44%) patients. IgM-RF titres decreased significantly (p<0.001), whereas anti-CCP showed little change (p=0.053). ANA titres increased significantly (p<0.001). The treatment response was not associated with changes in anti-CCP or IgM-RF titres during infliximab therapy (OR for a response in patients with a 50% anti-CCP decrease, 0.77 [95%CI, 0.16-3.58]; OR for a response in patients with a 50% IgM-RF decrease, 0.82 [95%CI, 0.16-4.13]). CONCLUSIONS: During infliximab therapy used to treat established RA, IgM-RF titres showed larger decreases than anti-CCP titres. Changes in IgM-RF and anti-CCP failed to correlate with the 48-week treatment response.

Meyer O, Nicaise-Roland P, Santos MD, Labarre C, Dougados M, Goupille P, Cantagrel A, Sibilia J, Combe B. · Rheumatology Unit, Assistance Publique Hôpitaux de Paris, Bichat University Hospital, 75018 Paris, France. · Arthritis Res Ther. · Pubmed #16469118 links to  free full text

Abstract: The objective of this study was to evaluate the potential of serially determined anti-cyclic citrullinated peptide (CCP) antibodies for predicting structural joint damage in patients with early rheumatoid arthritis (RA), compared to a single baseline determination. Ninety-nine RA patients with disease durations of less than one year and no history of disease-modifying antirheumatic drug therapy were followed prospectively for at least five years. Anti-CCP2 concentrations were measured using a second-generation ELISA. Sharp scores as modified by van der Heijde were determined on hand and foot radiographs. Anti-CCP2 antibodies were detected in 55.5% of patients at baseline and 63.6% at any time during the first three years. Presence of anti-CCP2 at any time during the first three years was associated with radiographic damage at baseline (odds ratio (OR), 3.66; 95% confidence interval (95% CI) 0.99-13.54) and with five year progression of the total Sharp score (OR, 3.17; 95% CI, 1.3-7.7), erosion score (OR, 5.3; 95% CI, 1.4-19.2) and joint space narrowing score (OR, 2.8; 95% CI, 1.15-6.8). The presence of anti-CCP2 or IgM RF at baseline did not predict these outcomes. Patients with negative anti-CCP2 tests throughout follow-up had less radiographic progression than patients with increasing anti-CCP2 concentrations; they did not differ from patients with decreasing anti-CCP2 antibody levels. HLADRB1* typing showed that progression of the mean modified Sharp score was not correlated with the presence of the shared epitope alleles. In conclusion, serially determined anti-CCP2 antibodies during the first three years of follow-up performs better than baseline determination for predicting radiographic progression in patients with early RA.

Meyer O, Labarre C, Dougados M, Goupille P, Cantagrel A, Dubois A, Nicaise-Roland P, Sibilia J, Combe B. · Service de Rhumatologie, CHU Bichat, AP-HP, Paris, France. · Ann Rheum Dis. · Pubmed #12525380 links to  free full text

Abstract: OBJECTIVE: To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). METHODS: 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. RESULTS: Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years. CONCLUSION: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.