Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment

The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30–6.75), 3.69 (2.67–4.62), 2.9 (2.39–4.65) and 3.71 (2.62–5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47–290 IU/ml) to 53 IU/ml (18–106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy

High IgA rheumatoid factor levels are associated with poor clinical response to tumour necrosis factor α inhibitors in rheumatoid arthritis

OBJECTIVE: To investigate whether rheumatoid factor isotypes and anti‐cyclic citrullinated peptide (anti‐CCP) antibodies are related to clinical response in patients with rheumatoid arthritis treated with tumour necrosis factor α (TNFα) inhibitors. METHODS: The study was carried out on 132 patients with advanced rheumatoid arthritis refractory to disease‐modifying antirheumatic drugs. Patients were treated with infliximab (n = 63), etanercept (n = 35) or adalimumab (n = 34). All patients completed 1 year of follow‐up, and 126 were evaluable for clinical response according to the disease activity score (DAS) criteria. IgM, IgA and IgG rheumatoid factors and anti‐CCP antibodies were assessed by ELISA both before anti‐TNFα treatment and 1 year later. RESULTS: The DAS response was reached in 66% of evaluable patients (61% infliximab, 65% etanercept and 76% adalimumab; p = 0.354). A significant reduction in the rheumatoid factor level was reported by all treatment groups after 1 year. The frequency of positive tests for the different antibodies did not differ between responders and non‐responders at baseline; however, significantly higher IgA rheumatoid factor levels were reported by the non‐responder group (130.4 U/ml (interquartile range 13.8–276.7) v 24.8 U/ml (10.2–90.8); p = 0.003). A significant decrease (p<0.001) in the levels of all rheumatoid factor isotypes in the responder group was reported after 1 year of treatment, whereas anti‐CCP antibody levels were not significantly affected. CONCLUSIONS: According to the clinical response, anti‐TNFα agents seem to reduce IgM, IgG and IgA rheumatoid factor levels. More interestingly, high pretreatment levels of IgA rheumatoid factor are associated with a poor clinical response to TNFα inhibitors

Rapid evaluation of notch stress intensity factors using the peak stress method with 3D tetrahedral finite element models: Comparison of commercial codes

The peak stress method (PSM) allows a rapid application of the notch stress intensity factor (NSIF) approach to the fatigue life assessment of welded structures, by employing the linear elastic peak stresses evaluated by FE analyses with coarse meshes. Because of the widespread adoption of 3D modeling of large and complex structures in the industry, the PSM has recently been boosted by including four-node and ten-node tetrahedral elements of Ansys FE software, which allows to discretize complex geometries. In this paper, a Round Robin among eleven Italian Universities has been performed to calibrate the PSM with seven different commercial FE software packages. Several 3D mode I, II and III problems have been considered to investigate the influence of (i) FE code, (ii) element type, (iii) mesh pattern, and (iv) procedure to extrapolate stresses at FE nodes. The majority of the adopted FE software packages present similar values of the PSM parameters, the main source of discrepancy being the stress extrapolation method at FE nodes