Key result
NAb titers measured with MGA and iLite bioassays were significantly correlated (Spearman r=0.9368), and a titer of 150 TRU/mL was identified as a biologically functional cut-point.
Why the study?
How do NAb titers measured by MGA and iLite bioassays correlate, and what is the biologically functional cut-point for NAb positivity in MS patients treated with IFNβ?
Observational (n=44)
How do NAb titers measured by MGA and iLite bioassays correlate, and what is the biologically functional cut-point for NAb positivity in MS patients treated with IFNβ?
NAb titers measured with MGA and iLite bioassays are highly comparable, and a titer of 150 TRU/mL serves as a biologically functional cut-point for reduced IFN-induced gene expression.
This is the authors' abstract. We don't add key points for this paper.
Interferon beta (IFNβ) is used as a first-line treatment in relapsing-remitting multiple sclerosis (MS). The occurrence of neutralizing antidrug antibodies (NAbs) against IFNβ may reduce treatment response. Therefore, clinical monitoring of NAbs is currently executed using bioassays, but several bioassays are available and it is unclear how well their readouts correlate. We made a comparison between 2 bioassays; myxovirus resistance protein A (MxA) gene expression assay (MGA) and iLite™ anti-Human IFNβ bioassay, to measure IFNβ-specific NAb titers in 44 MS patients. We further studied how NAb titers affected in vivo transcription of IFN-induced genes myxovirus resistant 1 (MX1) and C-X-C motif chemokine 10 (CXCL10), in addition to serum CXCL10 protein levels. There were significant correlations between NAb titer levels measured with MGA and iLite (Spearman r=0.9368). MX1 and CXCL10 gene expression was strongly induced by IFNβ and NAb positivity significantly reduced this expression. A NAb titer of 150 TRU/mL was observed to be a biological cut-point applicable to both assays, since MX1 and CXCL10 expression was greatly reduced or blocked in patients above this titer level. In conclusion, NAb titers measured with the MGA and iLite bioassays are comparable, but the threshold for positivity in both assays does not correspond to the biologically functional cut-point.
May support harmonizing NAb assays for MS research; leaves open prospective validation of the 150 TRU/mL cut-point before clinical adoption.
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Hermanrud et al. (2014) conducted an observational in Relapsing-remitting multiple sclerosis (MS) (n=44). Myxovirus resistance protein A (MxA) gene expression assay (MGA) and iLite™ anti-Human IFNβ bioassay was evaluated on Correlation between NAb titer levels measured with MGA and iLite (Spearman r=0.9368). NAb titers measured with MGA and iLite bioassays were significantly correlated (Spearman r=0.9368), and a titer of 150 TRU/mL was identified as a biologically functional cut-point.
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