Η κινητική των εξουδετερωτικών αντισωμάτων ένταντι της ιντερφερόνης-β σε ασθενείς με πολλαπλή σκλήρυνση, κατά τη διάρκεια των υποτρόπων της νόσου:
Creators: name: Γιαντζή, Βιργινία Ν.
Publisher: name: Aristotle University of Thessaloniki
Year: 2010
Subjects: Εξουδετερωτικά αντισώματα
Συνδετικά αντισώματα
Ιντερφερόνη-β
Πολλαπλή Σκλήρυνση
Neutralizing antibodies
Binding antibodies
Interferon-b
Multiple sclerosis

description: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterized by relapsing-remitting course that affects young adults causing considerable disability. The advent of interferon beta (IFN-β) in the treatment of relapsing-remitting MS (RRMS) changed the course of the disease by reducing the activity of the disease which is reflected by the amelioration of clinical and radiological parameters. IFN-β preparations possess immunogenic properties and induce the development of binding (Babs)- and neutralizing (Nabs)- antibodies to IFN-β. The development of Nabs is associated with attenuation of treatment effect of IFN-β and increase of disease activity. The established approach to treat relapses of MS is corticosteroid pulse therapy. In the present study we aimed to evaluate the impact of a 5-day intravenous methylprednisolone (IVMP) pulse on the kinetics of Nabs and Babs titers in patients with RRMS under treatment with IFN-β during acute relapse of the disease (subgroup A2). In order to assess the credibility of the binding and neutralizing assays used at the laboratory of B’ Department of Neurology, we evaluated the incidence of anti-interferon-β antibodies in patients with RRMS under treatment with IFN-β with concomitant inadequate response to their treatment, in a subgroup of patients (subgroup A1) experiencing a relapse of the disease and in a subgroup (subgroup B) presenting stable neurological status at the time of blood sampling. Observations made during the progression of the study, urged us to verify the liability of our results and for that purpose we assessed the sensitivity of the established, recommended by World Health Organization (WHO), binding and neutralizing assays. The results are summarized as follows: 1. Patients with RRMS under treatment with IFN-β exhibiting intermediate disease activity or poor response to IFN-β treatment, developed high percentage of Nabs and Babs. 2. Among the 3 IFN-β formulations, IFN-β-1b resulted more immunogenic in comparison to IFN-β-1a preparations. 3. A subset of patients although negative for Babs, developed Nabs. This finding suggests that mechanisms other than the presence of Nabs, may be responsible for the abolition of IFN-β bioactivity. 4. Methylprednisolone significantly reduces Nabs though not Babs titers, its effect is augmented up to 1 month post-course and remains up to approximately 6 months. 5. Initial Nabs titers determined their kinetics at the end of IVMP therapy. 6. EDSS reduction due to IVMP tended to be better in the Nabs-positive patients. 7. Western blot assay is more sensitive than ELISA for the detection of Babs, while Real-time-PCR confirms the results of the cytopathic effect assay for the detection of Nabs. Information on Nabs status in combination with MxA bioactivity, provide valuable assistance to the neurologist in treating patients, especially in those presenting inadequate response to their IFN-β treatment, thus supporting difficult or ambiguous decisions on whether to continue or terminate their therapy. Intravenous therapy with methylprednisolone during a relapse of the disease exerts beneficial effect on the resolution of symptoms and the decrease of Nabs titers, but its practical value in resolving the problematic issue of Nabs is limited, especially in regards to high Nabs levels of major clinical importance.
description: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterized by relapsing-remitting course that affects young adults causing considerable disability. The advent of interferon beta (IFN-β) in the treatment of relapsing-remitting MS (RRMS) changed the course of the disease by reducing the activity of the disease which is reflected by the amelioration of clinical and radiological parameters. IFN-β preparations possess immunogenic properties and induce the development of binding (Babs)- and neutralizing (Nabs)- antibodies to IFN-β. The development of Nabs is associated with attenuation of treatment effect of IFN-β and increase of disease activity. The established approach to treat relapses of MS is corticosteroid pulse therapy. In the present study we aimed to evaluate the impact of a 5-day intravenous methylprednisolone (IVMP) pulse on the kinetics of Nabs and Babs titers in patients with RRMS under treatment with IFN-β during acute relapse of the disease (subgroup A2). In order to assess the credibility of the binding and neutralizing assays used at the laboratory of B’ Department of Neurology, we evaluated the incidence of anti-interferon-β antibodies in patients with RRMS under treatment with IFN-β with concomitant inadequate response to their treatment, in a subgroup of patients (subgroup A1) experiencing a relapse of the disease and in a subgroup (subgroup B) presenting stable neurological status at the time of blood sampling. Observations made during the progression of the study, urged us to verify the liability of our results and for that purpose we assessed the sensitivity of the established, recommended by World Health Organization (WHO), binding and neutralizing assays. The results are summarized as follows: 1. Patients with RRMS under treatment with IFN-β exhibiting intermediate disease activity or poor response to IFN-β treatment, developed high percentage of Nabs and Babs. 2. Among the 3 IFN-β formulations, IFN-β-1b resulted more immunogenic in comparison to IFN-β-1a preparations. 3. A subset of patients although negative for Babs, developed Nabs. This finding suggests that mechanisms other than the presence of Nabs, may be responsible for the abolition of IFN-β bioactivity. 4. Methylprednisolone significantly reduces Nabs though not Babs titers, its effect is augmented up to 1 month post-course and remains up to approximately 6 months. 5. Initial Nabs titers determined their kinetics at the end of IVMP therapy. 6. EDSS reduction due to IVMP tended to be better in the Nabs-positive patients. 7. Western blot assay is more sensitive than ELISA for the detection of Babs, while Real-time-PCR confirms the results of the cytopathic effect assay for the detection of Nabs. Information on Nabs status in combination with MxA bioactivity, provide valuable assistance to the neurologist in treating patients, especially in those presenting inadequate response to their IFN-β treatment, thus supporting difficult or ambiguous decisions on whether to continue or terminate their therapy. Intravenous therapy with methylprednisolone during a relapse of the disease exerts beneficial effect on the resolution of symptoms and the decrease of Nabs titers, but its practical value in resolving the problematic issue of Nabs is limited, especially in regards to high Nabs levels of major clinical importance.