Dynamics of interferon-β modulated mRNA biomarkers in multiple sclerosis patients with anti-interferon-β neutralizing antibodies

Santos, Roseane Maria Maia; Weinstock‐Guttman, Bianca; Tamaño‐Blanco, Miriam; Badgett, Darlene; Zivadinov, Robert; Justinger, T.; Munschauer, Frederick E.; Ramanathan, Murali

doi:10.1016/j.jneuroim.2006.03.019

Cited by 40 publications

(24 citation statements)

References 31 publications

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“…New therapies will be focused on targeting specific pathological processes, especially those related to inflammation, at the appropriate stage of disease and on the basis of current activity. The same tools can also be used to monitor response to treatment 158 (including toxicity 159 ). Some preclinical examples include studies in which either IL-13 (which polarizes macrophages to the M2 state) or a ligand of resolving receptors on macrophages were effective in retarding the progression of atherosclerosis 160,161 .…”

Section: Future Implicationsmentioning

confidence: 99%

Inflammatory processes in cardiovascular disease: a route to targeted therapies

et al. 2016

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Inflammatory processes are firmly established as central to the development and complications of cardiovascular diseases. Elevated levels of inflammatory markers have been shown to be predictive of future cardiovascular events. The specific targeting of these processes in experimental models has been shown to attenuate myocardial and arterial injury, reduce disease progression, and promote healing. However, the translation of these observations and the demonstration of clear efficacy in clinical practice have been disappointing. A major limitation might be that tools currently used to measure ‘inflammation’ are insufficiently precise and do not provide information about disease site, activity, or discriminate between functionally important activation pathways. The challenge, therefore, is to make measures of inflammation that are more meaningful, and which can guide specific targeted therapies. In this Review, we consider the roles of inflammatory processes in the related pathologies of atherosclerosis and acute myocardial infarction (AMI), by providing an evaluation of the known and emerging inflammatory pathways. We highlight contemporary techniques to characterize and quantify inflammation, and consider how they might be used to guide specific treatments. Finally, we discuss emerging opportunities in the field, including current limitations and challenges that are the focus of ongoing study.

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Section: Future Implicationsmentioning

confidence: 99%

Inflammatory processes in cardiovascular disease: a route to targeted therapies

et al. 2016

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“…Diverse biomarkers, ranging from single nucleotide polymorphisms, mRNA (e.g., MxA, Stat1, TRAIL, and others), proteins (e.g., oligoadenylate synthetase activity, Mx protein, and  2 microglobulin), and metabolites (e.g., neopterin) to immune cell populations, have been investigated as potential IFN- biomarkers (18)(19)(20). However, they were not useful predictors of MRI and clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

Uher

Fellows

Horáková

et al. 2017

Journal of Lipid Research

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Interferon- (IFN-) treatment is one of the most widely used disease-modifying treatments for multiple sclerosis (MS). The efficacy of recombinant human IFN- for relapsing MS has been established by multiple double-blind placebo-controlled multi-center trials (1-3). IFN- can delay the conversion to clinically definite MS (CDMS) in patients with a first demyelinating event (4-6), which supports early intervention with IFN-.MRI atrophy measures of brain volume and gray matter, white matter, and lateral ventricle volumes provide quantitative measures of global and tissue-specific brain volumes (7-9). Brain atrophy is useful for evaluating disease progression and therapeutic efficacy in MS (7) because it is a predictor of physical disability, cognitive dysfunction, and quality of life (10). However, there is a lack of effective serum biomarkers capable of predicting atrophy in MS patients.There is considerable inter-individual variability of IFN1a effectiveness among MS patients. Phase III studies of IFN- indicate a 30-40% general clinical benefit, although the response varies significantly among MS patients. On MRI, approximately 40% of patients show complete suppression of new contrast-enhancing lesions (CELs), whereas 20% of patients have less than 70% suppression

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“…Neurologists can prevent medication non-adherence by building an alliance with patients to help them achieve their goals with treatment that works. Practically, non-compliance can be identified by injecting IFNb in the hospital and checking MxA gene expression after 3-4 h [2,13,15,37].…”

Section: Discussionmentioning

confidence: 99%

One-year evaluation of factors affecting the biological activity of interferon beta in multiple sclerosis patients

et al. 2010

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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.

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Dynamics of interferon-β modulated mRNA biomarkers in multiple sclerosis patients with anti-interferon-β neutralizing antibodies

Cited by 40 publications

References 31 publications

Inflammatory processes in cardiovascular disease: a route to targeted therapies

Inflammatory processes in cardiovascular disease: a route to targeted therapies

Serum lipid profile changes predict neurodegeneration in interferon-β1a-treated multiple sclerosis patients

One-year evaluation of factors affecting the biological activity of interferon beta in multiple sclerosis patients

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