Real-time TaqMan assay for myxovirus resistance protein (MxA) mRNA: a robust marker of interferon beta bioactivity in patients with multiple sclerosis

2007 ◽  
Vol 13 (1_suppl) ◽  
pp. 49-52 ◽  
Author(s):  
A.R. Pachner
Keyword(s):  
Multiple Sclerosis ◽  
Real Time ◽  
Messenger Rna ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Therapeutic Option ◽  
Surrogate Marker ◽  
Taqman Assay ◽  
The Real ◽  
Resistance Protein

For many patients suffering from MS, interferon beta (IFNβ) is an effective therapeutic option; however, some patients who receive long-term IFNβ therapy for relapsing-remitting MS (RRMS) develop neutralizing antibodies (NAbs) that affect IFNβ efficacy. It is therefore important to evaluate patients' therapeutic response to IFNβ over time. Myxovirus resistance protein A (MxA), a surrogate marker of individual immunologic response to IFNβ, may be a useful tool for assessing IFNβ immunogenicity. The real-time TaqMan assay for MxA messenger RNA (mRNA) has several distinct advantages, including the ability to amplify and complete quantitative analyses in one step, a high degree of quality control and prior experience and confidence in the field of quantitative viral diagnostics. The real-time TaqMan assay for MxA mRNA can be incorporated as a component of IFNβ therapy to evaluate patients during the course of treatment. Multiple Sclerosis 2007; 13: S49—S52. http://msj.sagepub.com

Prevalence of anti-drug antibodies against interferon beta has decreased since routine analysis of neutralizing antibodies became clinical practice

2012 ◽  
Vol 18 (12) ◽  
pp. 1775-1781 ◽  
Author(s):  
Roger Jungedal ◽  
Malin Lundkvist ◽  
Elin Engdahl ◽  
Ryan Ramanujam ◽  
Helga Westerlind ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Practice ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Protein A ◽  
Routine Data ◽  
Cross Sectional ◽  
Resistance Protein ◽  
Multiple Sclerosis Patients ◽  
Sectional Analysis

Background: Neutralizing antibodies (NAbs) against interferon beta (IFNβ) lead to loss of treatment efficacy in multiple sclerosis patients. The seroprevalence of NAbs in multiple sclerosis patients treated with IFNβ during 2003–2004 was 32% in a cross-sectional analysis of routine data. Objectives: The aim of this study was to investigate whether the seroprevalence of NAbs, the levels of NAb titres and the IFNβ preparations used for treatment of multiple sclerosis patients had changed in 2009–2010. Methods: This study included 1296 patients, analysed for NAbs with the myxovirus resistance protein A gene expression assay in 2009–2010. Results: The seroprevalence of NAbs had decreased to 19% in 2009–2010, which is significantly lower compared with the previous study in 2003–2004 ( p<0.0001). This decrease was attributed to the IFNβ-1a preparations only, not to IFNβ-1b. The frequency of patients with high positive titres decreased the most, from 16% to 7% ( p<0.0001). Conclusions: NAb seroprevalence has decreased since NAb monitoring became clinical practice in 2003, especially for patients with high NAb titres. This might be due to the stricter monitoring of NAb titres that prompt NAb positive patients to stop treatment, to preferential use of less immunogenic drugs and to alteration of drug formulations.

scholarly journals Neutralizing antibodies and fatigue as predictors of low response to interferon-beta treatment in patients with multiple sclerosis

BMC Neurology ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Philippe Manceau ◽  
Clotilde Latarche ◽  
Sophie Pittion ◽  
Gilles Edan ◽  
Jérôme de Sèze ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta

Neutralizing antibodies in multiple sclerosis: a complex impact on interferon responses, magnetic resonance imaging findings and clinical outcomes

2007 ◽  
Vol 13 (1_suppl) ◽  
pp. 53-62 ◽  
Author(s):  
A.T. Reder
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Clinical Effect ◽  
First Year ◽  
Trial Duration ◽  
Cross Sectional ◽  
Immune Biomarkers ◽  
Interferon Responses ◽  
Clinical Worsening

Interferon beta (IFN-β) therapy reduces relapse rate, MRI lesion development, and delays the progression of disability in relapsing forms of multiple sclerosis. As with other protein therapies, some patients develop neutralizing antibodies (NAbs) that could limit the efficacy of IFN-β. The clinical impact of NAbs is hotly debated. Non-standardized NAb assays, NAb persistence and disappearance, plus a six-month lag before a clinical effect, different IFN-β species and formulations, variable trial duration, have made interpretation of the significance of NAbs a challenging task. There is a correlation between the presence of NAb and reduced efficacy of IFN-β therapy in two- to four-year trials. However, patients destined to become NAb positive do better in the first year of IFN-β therapy. Patients with clinical worsening have surprisingly low NAb frequency and titers. Understanding the true clinical implications of NAbs will require well-controlled longitudinal studies instead of simple cross-sectional analyses, plus innovative trial designs with immune biomarkers. Multiple Sclerosis 2007; 13: S53—S62. http://msj.sagepub.com

Application of Quantitative Real-Time PCR in the Detection of Prion-Protein Gene Species-Specific DNA Sequences in Animal Meals and Feedstuffs

2006 ◽  
Vol 69 (4) ◽  
pp. 891-896 ◽  
Author(s):  
FEDERICA BELLAGAMBA ◽  
SERGIO COMINCINI ◽  
LUCA FERRETTI ◽  
FRANCO VALFRÈ ◽  
VITTORIO M. MORETTI
Keyword(s):  
Real Time ◽  
Prion Protein ◽  
Dna Sequences ◽  
Real Time Pcr ◽  
Animal Feed ◽  
Quantitative Estimation ◽  
Taqman Assay ◽  
Quantitative Real Time Pcr ◽  
The Real ◽  
Species Specific

This study describes a method for quantitative and species-specific detection of animal DNA from different species (cattle, sheep, goat, swine, and chicken) in animal feed and feed ingredients, including fish meals. A quantitative real-time PCR approach was carried out to characterize species-specific sequences based on the amplification of prion-protein sequence. Prion-protein species-specific primers and TaqMan probes were designed, and amplification protocols were optimized in order to discriminate the different species with short PCR amplicons. The real-time quantitative PCR approach was also compared to conventional species-specific PCR assays. The real-time quantitative assay allowed the detection of 10 pg of ruminant, swine, and poultry DNA extracted from meat samples processed at 130°C for 40 min, 200 kPa. The origin of analyzed animal meals was characterized by the quantitative estimation of ruminant, swine, and poultry DNA. The TaqMan assay was used to quantify ruminant DNA in feedstuffs with 0.1% of meat and bone meal. In conclusion, the proposed molecular approach allowed the detection of species-specific DNA in animal meals and feedstuffs.

Differing immunogenic potentials of interferon beta preparations in multiple sclerosis patients

2006 ◽  
Vol 12 (6) ◽  
pp. 731-737 ◽  
Author(s):  
C Gneiss ◽  
P Tripp ◽  
F Reichartseder ◽  
R Egg ◽  
R Ehling ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
First Line ◽  
Positive Group ◽  
Treatment Groups ◽  
First Line Therapy ◽  
Multiple Sclerosis Patients ◽  
Patients Experience ◽  
Insight Into

Interferon beta (IFNβ) is a first-line therapy for multiple sclerosis (MS). However, some patients experience a decline in efficacy with continued therapy due to the development of anti-IFNβ neutralizing antibodies (NAb). We investigated the frequency of NAb cross-sectionally in 846 MS patients who were receiving IFNβ-1b, IFNβ-1a im, or IFNβ-1a sc. The frequency of NAb in patients receiving IFNβ-1a im was lower (5%) than in patients treated with any other form of IFNβ (22-35%) (P < 0.0001). Binding antibodies (BAb) were measured in 808 patients. The frequency differed significantly between treatment groups, ranging from 45% (IFNβ-1a im) to 88% (IFNβ-1b). The proportion of NAb-positive patients within the BAb-positive group differed significantly among treatment groups, ranging between 12% (IFNβ-1a im) and 51% (IFNβ-1a sc). The median NAb titer from all IFNβ-1a-treated patients was higher than from IFNβ-1b-treated patients (446 versus 171 NU/mL, P = 0.04). Among NAb-positive patients, the frequency of NAb titers > 100 NU/mL was 71% for IFNβ-1a compared with 58% for IFNβ-1b (P = 0.04). Except for conflicting data regarding IFNβ-1a sc, the results are generally consistent with the literature and together with the differing proportion of NAb-positive patients within the BAb-positive group, provide further insight into the immunogeni-city of the IFNβ preparations.

Optimizing Immunomodulatory Therapy with Interferon Beta in Patients with Multiple Sclerosis

2010 ◽  
Vol 12 (4) ◽  
pp. 147-154 ◽  
Author(s):  
Said Masri ◽  
Andreas Blodau ◽  
Norbert Zessack ◽  
Michael Lang ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
Therapeutic Option ◽  
Scale Model ◽  
Term Therapy ◽  
Disability Progression ◽  
Treatment Optimization ◽  
Long Term Therapy ◽  
Immunomodulatory Therapies

Patients with multiple sclerosis (MS) may change immunomodulatory therapies if efficacy is considered inadequate or if adverse drug reactions occur. Identifying potential candidates for therapy adjustment is an important aspect of treatment optimization. This study aimed to evaluate the safety and efficacy of interferon beta-1a (IFNβ-1a), 44 μg subcutaneously (SC) three times weekly, in patients with relapsing MS following a change from another long-term therapy and to identify potential candidates for therapy adjustment. Patients were followed for 12 months. Candidates for therapy adjustment were identified using a three-scale model of treatment efficacy (relapses, disability progression, and magnetic resonance imaging). For 76.4% of patients, insufficient efficacy of the previous therapy was the main reason for changing to IFNβ-1a 44 μg. At baseline, 70.6% of patients fulfilled the criteria for recommendation for therapy adjustment; after 12 months on IFNβ-1a 44 μg, this percentage decreased to 16.6%. The incidence of adverse events (AEs) decreased between week 4 (40.6% of patients) and month 12 (12.8%). Influenza-like symptoms were the most common AE, occurring in 28.3% of patients. This study supports IFNβ-1a, 44 μg SC three times weekly, as a therapeutic option for patients in need of therapy adjustment.

Persistence of neutralizing antibodies after discontinuation of IFNβ therapy in patients with relapsing-remitting multiple sclerosis

2006 ◽  
Vol 12 (3) ◽  
pp. 247-252 ◽  
Author(s):  
Bodil Petersen ◽  
Klaus Bendtzen ◽  
Nils Koch-Henriksen ◽  
Mads Ravnborg ◽  
Christian Ross ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Cytopathic Effect ◽  
Serum Levels ◽  
Neutralizing Capacity ◽  
Relapsing Remitting ◽  
Long Time ◽  
Relapsing Remitting Multiple Sclerosis

Objective The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNβ) after discontinuation of IFNβ therapy. Background A large proportion of patients treated with recombinant IFNβ for multiple sclerosis (MS) develop therapy-induced NABs. Knowledge of persistence of NABs after discontinuation of therapy is limited. Design/patients: A retrospective follow-up study of patients treated in Denmark for relapsing-remitting (RR) MS with IFNβ for at least 12 months. NAB-positive patients, who discontinued therapy, were followed up with measurements of NABs. Methods We measured NAB-neutralizing capacity and NAB titres a.m. Kawade using a clinically validated cytopathic effect assay. Results Thirty-seven patients were included. Mean follow-up time was 22 months. Of the 29 patients with a NAB titre at or above 25 prior to termination of therapy, only three patients reverted to a titre below 25. Of these, two had a titre below 200 and one patient a titre of 600 at the last examination before treatment stop. The longest post-treatment follow-up during which a patient maintained NAB positivity was 59 months. Conclusion NABs against IFNβ, especially with high titres, tend to persist for a long time after discontinuation of IFNβ therapy. NABs should always be measured before reinstitution of IFNβ treatment in NAB-positive patients.

Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis

2009 ◽  
Vol 15 (3) ◽  
pp. 323-328 ◽  
Author(s):  
M Ravnborg ◽  
K Bendtzen ◽  
O Christensen ◽  
PEH Jensen ◽  
D Hesse ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Primary Outcome ◽  
Protein A ◽  
Control Group ◽  
Interferon Β ◽  
Gene Assay ◽  
Resistance Protein ◽  
Polymerase Chain

Background It is unknown whether immunosuppression of patients who have developed interferon-β (IFN-β) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood. Objective We wanted to test whether immunosuppression with cyclic methylprednisolone (MP) in combination with azathioprine (AZA) for 6 months accelerates recovery of IFN-β bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-β. Methods We included 13 patients with MS with NAbs and a low IFN-β bioavailability detected by the MxA-mRNA response in a descriptive, non-randomized trial. Another 14 NAb-positive patients with a low MxA-mRNA response served as controls. The primary outcome was the fraction of patients who regained an MxA-mRNA response to IFN-β. NAbs were measured by means of a clinically validated cytopathic effect assay and a new reporter gene assay. The in-vivo MxA-mRNA response was measured by real-time polymerase chain reaction. Results A total of 11 patients in the treatment group completed the trial. In all, two of these 11 patients regained an in-vivo MxA-mRNA response as compared to one of 14 patients in the control group. Conclusion Treatment with AZA and cyclic MP for 6 months has little or no effect on IFN-β bioactivity in NAb-positive patients with MS.

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