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MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients.

ABSTRACT: Even though anti-interferon beta (IFN?) antibodies are the main determinants of IFN? bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFN? biological activity in IFN?-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to evaluate the kinetics of bioactivity loss in blood samples obtained every 6 months after therapy initiation, MxA and interferon receptor isoform/subunit mRNA were quantified by real-time PCR, anti-IFN? binding antibodies were detected by radioimmunoprecipitation, and neutralizing antibodies by cytopathic effect inhibition assay. Clinical measures of disease activity and disability progression were also obtained at all time points. We found that, at the individual-patient level, the response to IFN? therapy was extremely heterogeneous, including patients with stable or transitory, early or late loss of IFN? bioactivity, and patients with samples lacking MxA mRNA induction in spite of absence of antibodies. No interferon receptor isoform alterations that could explain these findings were found. At the group level, none of these biological features correlated with the measures of clinical disease activity or progression. However, when MxA mRNA was evaluated not at the single time point as a dichotomic marker (induced vs. non-induced), but as the mean of its values measured over the 6-to-24 month period, the increasing average MxA predicted a decreasing risk of short-term disability progression, independently from the presence of relapses. Therefore, a more bioactive treatment, even if unable to suppress relapses, reduces their severity by an amount that is proportional to MxA levels. Together with its feasibility in the routine laboratory setting, these data warrant the quantification of MxA mRNA as a primary tool for a routine monitoring of IFN? therapy.

SUBMITTER: Serana F

PROVIDER: S-EPMC3986392 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients.

Serana Federico F Imberti Luisa L Amato Maria Pia MP Comi Giancarlo G Gasperini Claudio C Ghezzi Angelo A Martinelli Vittorio V Provinciali Leandro L Rottoli Maria Rosa MR Sotgiu Stefano S Stecchi Sergio S Vecchio Michele M Zaffaroni Mauro M Cordioli Cinzia C Capra Ruggero R

PloS one 20140414 4

Even though anti-interferon beta (IFNβ) antibodies are the main determinants of IFNβ bioactivity loss and Myxovirus-resistance protein A (MxA) is the most established marker of IFNβ biological activity in IFNβ-treated multiple sclerosis patients, their usefulness in the routine clinical practice is still debated. Therefore, 118 multiple sclerosis patients naïve for treatment were enrolled for a 3-year longitudinal observational study mimicking the conditions of a real-world setting. In order to ...[more]

PMID: 24733382

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Project description:BackgroundSeveral concerns exist on the immunogenicity of SARS-CoV-2 vaccines in multiple sclerosis (MS) subjects due to their immunomodulating disease modifying therapies (DMTs). Here we report a comparison of the humoral response to BNT162b2-mRNA coronavirus (COVID)-19 vaccine and the immunological phenotype in a cohort of 125 MS subjects undergoing different DMTs, with no history of SARS-CoV-2 infection.MethodsWe collected serum and blood samples at the first day of vaccine (T0) and 21 days after the second vaccine dose (T1) from 125 MS subjects, undergoing eight different DMTs. Sera were tested using the Elecsys anti-SARS-CoV-2-IgG assay for the detection of IgG antibodies to SARS-CoV-2 spike protein. The anti-spike IgG titres from MS subjects were compared with 24 age- and sex-matched healthy controls (HC). Percentage and absolute number of B and T lymphocytes were evaluated by cytofluorimetric analysis in the same study cohort.ResultsWhen compared with SARS-CoV-2 IgG levels in HC (n = 24, median 1089 (IQR 652.5-1625) U/mL), we observed an increased secretion of SARS-CoV-2 IgG in interferon-beta 1a (IFN)-treated MS subjects (n = 22, median 1916 (IQR 1024-2879) U/mL) and an impaired humoral response in MS subjects undergoing cladribine (CLAD) (n = 10, median 396.9 (IQR 37.52-790.9) U/mL), fingolimod (FTY) (n = 19, median 7.9 (IQR 4.8-147.6) U/mL) and ocrelizumab (OCRE) (n = 15, median 0.67 (IQR 0.4-5.9) U/mL) treatment. Moreover, analysis of geometric mean titre ratio (GMTR) between different DMT's groups of MS subjects revealed that, when compared with IFN-treated MS subjects, intrinsic antibody production was impaired in teriflunomide (TERI)-, natalizumab (NAT)-, CLAD-, FTY- and OCRE-, while preserved in DMF- and GA-treated MS subjects.ConclusionHumoral response to BNT162b2-mRNA-vaccine was increased in IFN-treated MS subjects while clearly blunted in those under CLAD, FTY and OCRE treatment. This suggests that the DMTs could have a key role in the protection from SARS-CoV-2 related disease and complication in MS subjects, underlying a novel aspect that should be considered in the selection of the most appropriate therapy under COVID-19 pandemic.

Dataset Information

MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients.

Publications

MxA mRNA quantification and disability progression in interferon beta-treated multiple sclerosis patients.

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