Anti-citrullinated peptide antibodies and the progression of radiographic joint erosions in patients with early rheumatoid arthritis treated with FIN-RACo combination and single disease-modifying antirheumatic drug strategies.

OBJECTIVES: To evaluate the impact of antibodies to cyclic citrullinated peptide (ACPAs) on radiographic progression in patients with early rheumatoid arthritis (RA) initially treated either with a combination of 3 disease-modifying antirheumatic drugs (DMARDs) or with a single DMARD. METHODS: This study included 129 patients with early active RA initially randomised to treatment either with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and prednisolone (FIN-RACo) (n=69) or with a single DMARD (initially sulfalasalazine) with or without prednisolone (SINGLE) (n=60). After 2 years, the use of DMARDs and prednisolone became unrestricted. Radiographic progression in hands and feet was assessed at baseline and at 1, 2, 3, 4 and 5 years. ACPAs at baseline were determined with enzyme immunoassay. RESULTS: ACPAs were positive in 92 (71%) patients. ACPA-positive vs. negative patients were more frequently rheumatoid factor (RF) positive (83% vs. 22%, p<0.001) and had an erosive disease (54% vs. 22%, p<0.001) at baseline. The presence of ACPA was associated with radiographic progression in FIN-RACo group even when the impact of RF was controlled; the radiographic progression was remarkably slower in ACPA-negative than in ACPA-positive cases (RF adjusted change over time between groups p=0.034). In the SINGLE group, the radiographic changes progressed parallel in ACPA-negative and positive patients. CONCLUSIONS: Most ACPA-positive RA patients have joint erosions already at diagnosis. ACPA positivity in early RA was related to radiographic progression even in patients treated initially with the FIN-RACo regimen. The initial FIN-RACo therapy seems to slow down the progression of joint damage in ACPA-negative patients.

Antineutrophil cytoplasmic antibodies in patients with early rheumatoid arthritis: an early marker of progressive erosive disease.

OBJECTIVE: To evaluate the clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with early rheumatoid arthritis (RA), as well as the possible predictive role of ANCA. We also assessed the overlap of ANCA with other specific serologic markers of RA. METHODS: Eighty-two RA patients with symptoms for < or = 12 months were studied for the presence of ANCA by immunofluorescence and specific enzyme immunoassays. ANCA were determined and clinical, radiographic, and laboratory data were collected at study entry and later at 12, 36, 60, and 84 months. RESULTS: In 2 patients, the first serum samples (obtained at study entry) were no longer available for the determination of ANCA. Perinuclear ANCA (pANCA) were found in 40 patients (50%), and atypical cytoplasmic ANCA were found in 3 patients (4%) at study entry. Perinuclear ANCA-positive patients were significantly more frequently positive for rheumatoid factor (78%) than were ANCA-negative patients (54%) (P = 0.0297). Fifty-five percent of pANCA-positive patients and 22% of ANCA-negative patients were positive for antiperinuclear factor (P = 0.0044). Similarly, pANCA-positive patients had antikeratin antibodies more frequently than did ANCA-negative patients (35% versus 20%). During a 7-year followup, the progress of radiographic joint destruction, assessed with Larsen scores, was significantly more rapid in patients who were pANCA positive at study entry than in those who were ANCA negative (P = 0.0015). Also, the mean titer of pANCA at study entry was significantly higher in those patients who subsequently had advanced radiographic joint destruction at 60 and 84 months. The association of pANCA with rapid radiographic destruction in patients with early RA was further corroborated by a logistic regression analysis that selected pANCA positivity as an independent and statistically significant predictor of rapid radiographic joint destruction. CONCLUSION: In patients with early RA, pANCA are associated with specific serologic markers of RA and predict rapid radiographic joint destruction.

Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of severe disease with associated nephropathy.

OBJECTIVE: To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy. METHODS: A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay. RESULTS: Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (+/- SD) pANCA log titers (103 +/- 5.6 versus 27 +/- 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA-associated nephropathy. CONCLUSION: Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.

Polymerase chain reaction assay with urine specimens in the diagnosis of acute chlamydia trachomatis infection in women.

OBJECTIVE: The purpose of this study was to evaluate the benefits achievable by Amplicor polymerase chain reaction (PCR) (F. Hoffmann-LaRoche Ltd., Basel, Switzerland) with urine specimens in addition to PACE 2 (Gen-Probe, Inc., San Diego, California) assay with cervical swab specimens in the diagnosis of Chlamydia trachomatis in women. METHODS: Cervical and urine specimens from 286 women were tested for C. trachomatis by PACE 2 and Amplicor PCR, respectively. All urine specimens were analyzed undiluted and diluted 1:10 to detect and eliminate possible PCR inhibition. A confirmatory PCR assay using major outer membrane protein-based primers (MOMP-PCR) was used on urine specimens that were positive by PCR from women who were negative by PACE 2 with cervical swab specimens. RESULTS: Of the endocervical specimens, 26 were positive by the PACE 2 assay. The PCR with urine was positive in 21 of these patients. When the urine specimens were analyzed diluted 1:10, 4 of the 5 PCR-negative specimens from PACE 2-positive patients turned positive by the PCR. Additionally, 4 urine specimens from PACE 2-negative women were positive by the PCR with urine, and 3 of them could be confirmed by MOMP-PCR. Altogether, 29 women were found to be positive for C. trachomatis by either of the two assays. CONCLUSIONS: By using the PCR with urine specimens, an 11% increase in sensitivity could be achieved in addition to that obtained by PACE 2 assay with cervical swab specimens. In the present material, however, the increased sensitivity was reversed by the presence of PCR inhibitors in 14% of the female urine specimens. Amplicor PCR with urine specimens can undoubtedly be recommended for the diagnosis of chlamydial infections in women. However, constant monitoring of the PCR inhibition seems highly advisable to obtain full benefit of the sensitivity of the PCR.