Circulating autoantibodies against neutrophils (ANCA) are a distinctive finding in patients with Wegener's granulomatosis (WG). B-lymphocyte activating factor (BAFF) promotes autoantibody production by increasing B cell survival and proliferation. We investigated serum BAFF levels (s-BAFF) in a WG patient cohort in relation to ANCA titers and disease activity. Baseline data were obtained in twenty-two WG patients (55% female, age 44 years, disease duration 1 year). S-BAFF was determined by capture ELISA and associations between s-BAFF, clinical (Birmingham Vasculitis Activity Score (BVAS), Vasculitis Damage Index (VDI) and Disease Extent Index (DEI)) and biochemical (C-reactive protein (CRP), IgG and ANCA) disease measures were analysed in a cross sectional as well as longitudinal analysis. S-BAFF was increased in WG patients compared to healthy controls (1.8 vs. 0.55 ng/ml, p < 0.01). S-BAFF was higher in ANCA negative than ANCA-positive WG sera (2.16 vs. 1.29 ng/ml, p < 0.01), correlated independently and inversely with ANCA levels (Rs -0.48, p < 0.01) but did not correlate with CRP, BVAS, DEI or VDI scores. Individual s-BAFF profiles were stable over time in 68% of patients. The finding of a negative correlation between ANCA levels and s-BAFF that is independent of steroid treatment indicates that BAFF does not directly drive ANCA production in WG.
Immunogenicity is a frequent cause of secondary non-response to tumour necrosis factor (TNF) inhibitors. Drug level measurement and detection of antidrug antibodies have been shown to be cost effective and clinically relevant, and a large number of assays are available for these purposes. It is, however, difficult to compare assays and translate results into clinical meaningful information due to different methodological approaches and a lack of assay standardization. We have analysed infliximab drug levels and antidrug antibodies in 107 patient samples using enzyme-linked immunoassays (ELISA), immunofluorometric assays (IFMA) and reporter-gene assays (RGA). The RGA gave the lowest results for drug levels, whereas the IFMA detected the highest number of antidrug antibody positive sera. Applying individualized therapeutic ranges to each assay resulted in agreement among all three assays in 74% of samples for drug levels and 98% of samples for antidrug antibodies. We found that TNF inhibitor monitoring assays measure on different scales and that the agreement between quantitative results is limited. However, interassay differences can partially be overcome by assay-individualized translations of quantities into categories, which also is necessary for a meaningful clinical application. Our data demonstrate that assays should not be used interchangeably and that direct comparison of quantitative drug levels obtained with different assays should be avoided.
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