Interferon-β bioactivity measurement in multiple sclerosis: feasibility for routine clinical practice

Abstract

Our data suggest that for IFN beta bioactivity screening a single post-injection measurement seems reasonable. However, MxA induction measurement based on both pre- and post-IFN beta injection samples at second measurement is somewhat more precise in determining ultimate IFN beta bioactivity status.

One-year evaluation of factors affecting the biological activity of interferon beta in multiple sclerosis patients

“…In fact, MxA is a well defined ISG up-regulated by type I IFNs (IFNa and b) [30], but not by IFNc [31]. Along with several authors [1, 5-7, 14-16, 26], we have shown that MxA gene expression is significantly increased in treated compared to untreated patients [2,3,12,13,24], and that MxA gene expression is abolished by the presence of anti-IFNb BAbs or NAbs [2,4,[8][9][10][11][12][13][14][15][16] as well as by any other inhibiting factors [32]. Moreover, it was demonstrated that MxA gene expression correlates with altered expression of molecules involved in MS pathogenesis and/or IFNb clinical efficacy (e.g., matrix metalloproteinases, tumor necrosis factor-related apoptosis-inducing ligand [3,13,14]).…”

“…The problem of a false-negative result due to IFNb receptor saturation can be easily overcome by the following repetition of MxA mRNA quantification; particularly, reevaluating MxA gene expression after a 7-day withdrawal period and analyzing blood samples 12 h before and 12 h after IFNb injection [15].…”

“…All reactions were performed in duplicate. Relative quantisation of all targets was calculated by the comparative cycle threshold (Ct) Choice of the threshold for MxA mRNA Currently, there is no consensus regarding the exact definition of biologically relevant MxA gene expression; some authors propose the +2SD [5,6] cut-off while others propose the +3SD [2,3,12,15,[23][24][25][26] cut-off. Using the +3SD definition, MxA mRNA measurement was more sensitive than specific for discrimination of IFNb untreated and treated patients [23].…”

“…MxA show an increased level in patients after the first IFNb injection [2,3], whereas in a relevant percentage of patients during IFNb therapy, MxA expression is inhibited, mainly due to the development of BAbs and/or NAbs [1,2,[4][5][6][7][8][9][10][11][12][13][14][15][16]. On these grounds, MxA can be considered a biomarker intended to substitute for clinical endpoint, i.e., a surrogate endpoint.…”

Neutralizing antibodies in interferon beta treated patients with multiple sclerosis: knowing what to do now

“…However, since there are inter-individually different response curves of the MxA mRNA expression, a small proportion of patients may be classified false-positively [21][22][23]. To minimize this potential error it would be ideal to compare individual MxA mRNA responses on IFNb therapy with the respective responses at treatment initiation of the same individual [24]. In this issue of the Journal S. Malucchi et al have set out to evaluate BAbs and NAbs in 167 patients with MS after 1 year of treatment with IFNb.…”