title: Therapeutic Plasma Exchange in Multiple Sclerosis Patients with Abolished Interferon-beta Bioavailability.
abstract: BACKGROUND
  Neutralizing antibodies (NAb) to interferon-beta (IFN-β) are associated with reduced bioactivity and efficacy of IFN-β in multiple sclerosis (MS). The myxovirus resistance protein A (MxA) gene expression is one of the most appropriate markers of biological activity of exogenous IFN-β. We hypothesized that therapeutic plasma exchange (TPE) can restore the ability of IFN-β to induce the MxA mRNA expression and that maintenance plasmapheresis can sustain the bioavailability of IFN-β.
  
  
  METHODS
  Eligible patients underwent 4 primary separate plasma exchange sessions. After the induction TPE sessions, they were transferred to maintenance plasmapheresis. Bioactivity of IFN-β was expressed as in vivo MxA mRNA induction in whole blood using RT-qPCR.
  
  
  RESULTS
  Six patients with low IFN-β bioavailability detected by the MxA mRNA response were included. Four patients became biological responders after induction plasmapheresis. In 2 patients an increase of MxA mRNA expression was found, but the values persisted below the cut-off and the patients remained as "poor biological responders". The effect of maintenance plasmapheresis was transient: MxA mRNA expression values reverted to the baseline levels after 1-2 months.
  
  
  CONCLUSIONS
  Therapeutic plasma exchange is able to restore the bioavailability of IFN-β in the majority of studied patients, but the effect of TPE on the IFN-β bioavailability was transient.
authors.affiliation: Clinic of Neurology and Neurosurgery, Faculty of Medicine, Vilnius University, Center of Neurology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Natasa
authors.initials: N
authors.lastname: Giedraitiene
authors.affiliation: Clinic of Neurology and Neurosurgery, Faculty of Medicine, Vilnius University, Center of Neurology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Gintaras
authors.initials: G
authors.lastname: Kaubrys
authors.affiliation: Clinic of Neurology and Neurosurgery, Faculty of Medicine, Vilnius University, Center of Neurology, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Rasa
authors.initials: R
authors.lastname: Kizlaitiene
authors.affiliation: Center for Laboratory Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Loreta
authors.initials: L
authors.lastname: Bagdonaite
authors.affiliation: Internal Medicine Clinic, Family Medicine and Oncology, Faculty of Medicine, Vilnius University, Center of Hematology, Oncology and Transfusion Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Laimonas
authors.initials: L
authors.lastname: Griskevicius
authors.affiliation: Center for Hematology, Oncology and Transfusion Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Vilma
authors.initials: V
authors.lastname: Valceckiene
authors.affiliation: Center for Hematology, Oncology and Transfusion Medicine, Vilnius University Hospital Santariskiu Clinics, Vilnius, Lithuania.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Stoskus
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D001682:Biological Availability; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000276:immunology / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000628:therapy*; D064547:Myxovirus Resistance Proteins / Q000378:metabolism; D010865:Pilot Projects; D010951:Plasma Exchange / Q000379:methods*; D010956:Plasmapheresis / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D057134:Antibodies, Neutralizing; D015415:Biomarkers; D064547:Myxovirus Resistance Proteins; D016899:Interferon-beta