Anti-interferon beta antibody titers strongly correlate between two bioassays and in vivo biomarker expression, and indicates that a titer of 150 TRU/mL is a biologically functional cut-point.
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.
Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital Solna , Stockholm, Sweden .
Christina
C
Hermanrud
Malin Lundkvist
ML
Ryner
Elin
E
Engdahl
Anna
A
Fogdell-Hahn
D057134:Antibodies, Neutralizing / Q000097:blood*; D001681:Biological Assay / Q000592:standards*; D015415:Biomarkers / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000097:blood / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000032:analysis*; D009103:Multiple Sclerosis / Q000097:blood*; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D059467:Transcriptome
D057134:Antibodies, Neutralizing; D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D064547:Myxovirus Resistance Proteins; D016899:Interferon-beta