title: One-year evaluation of factors affecting the biological activity of interferon beta in multiple sclerosis patients.
abstract: MxA is an antiviral protein induced by type I interferons (IFN) and some viruses; MxA gene expression is an appropriate marker for measuring biologic activity of exogenous IFNβ, as its induction indicates IFNAR receptor stimulation. A recent study has shown that measurement of MxA mRNA, after 1 year of treatment, predicts clinical responsiveness to IFNβ therapy. Loss of IFNβ bioactivity is mostly due to anti-IFNβ antibodies (both neutralizing and binding), non-compliance and receptor saturation. The aim of this study was to evaluate all possible causes of loss of IFNβ bioactivity after 1 year in treated patients. One hundred sixty-seven multiple sclerosis (MS) patients were included. One year after beginning IFNβ therapy, each patient underwent a blood test; MxA gene expression was measured by real time PCR, antiviral CPE assay to detect neutralizing antibodies (NAbs), and capture-ELISA (cELISA) to measure binding antibodies (BAbs). For MxA an upper normal threshold of 87 (RE) was considered, 20 TRU/mL was the threshold for NAbs, and 1 U for BAbs positivity. Thirty-seven out of 167 patients (22%) were MxA-negative; of these, 22 were both BAbs and NAbs+, whereas 12 were BAbs+ but Nabs-, and three were both BAbs and NAbs-. The following conclusions were drawn from the study: (1) MxA mRNA should be measured after 1 year of IFNβ therapy; (2) after 1 year of IFNβ treatment, absence of IFNβ bioactivity was detected in 22% of the patients; (3) different biological phenomena and reduced compliance explain this absence; (4) identification of the reason for absence of IFN bioactivity improves patients' management.
authors.affiliation: Neurologia 2, Centro Riferimento Regionale Sclerosi Multipla (CRESM), ASO S. Luigi Gonzaga, Regione Gonzole 10, 10043, Orbassano (Torino), Italy. sclerosi.multipla@sanluigi.piemonte.it
authors.forename: Simona
authors.initials: S
authors.lastname: Malucchi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gilli
authors.forename: Marzia
authors.initials: M
authors.lastname: Caldano
authors.forename: Arianna
authors.initials: A
authors.lastname: Sala
authors.forename: Marco
authors.initials: M
authors.lastname: Capobianco
authors.forename: Alessia
authors.initials: A
authors.lastname: di Sapio
authors.forename: Letizia
authors.initials: L
authors.lastname: Granieri
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D004361:Drug Tolerance / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D007155:Immunologic Factors; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta; D019204:GTP-Binding Proteins