Interferon-Beta Therapy Monitoring in Multiple Sclerosis Patients

Sottini, Alessandra; Capra, Ruggero; Serana, Federico; Chiarini, Marco; Caimi, Luigi

doi:10.2174/187153009787582379

Cited by 14 publications

(6 citation statements)

References 157 publications

(213 reference statements)

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“…A second mechanism in the failure to respond to IFN-β therapy is probably due to immunogenic factors leading to a decrease in the bioavailability of IFN-β. Development of NAbs is one of the main types but also others as the presence of different IFN receptor isoforms could contribute to this decrease [23] . Independently of the mechanism involved, a reduction of the expression of induced interferon responsive genes is detected including the MxA expression.…”

Section: Discussionmentioning

confidence: 99%

Baseline MxA mRNA Expression Predicts Interferon Beta Response in Multiple Sclerosis Patients

et al. 2014

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BackgroundMyxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection, mostly used to evaluate its bioactivity. There is little available data on clinical utility of baseline MxA mRNA status. The objective of the study is to investigate whether baseline MxA mRNA expression can predict relapse and disease progression in multiple sclerosis patients treated with interferon-beta.MethodsBaseline blood samples were obtained before the first interferon-beta dose was administered to evaluate MxA mRNA expression using real-time polymerase chain reaction (PCR). Demographic and clinical variables were prospectively recorded to define treatment responder and non responder groups.Results104 patients were included in the study. Baseline MxA mRNA expression was significantly lower in the group of patients who met the definition of responders (1.07 vs 1.95, Student t test, p<0.0001). A threshold of 1.096 was established using Receiver Operating Characteristic analysis to differentiate between responders and non-responders (sensitivity 73.9%, specificity 69.0%). Survival analysis using this threshold showed that time to next relapse (p<0.0001) and to EDSS progression (p = 0.01) were significantly higher in patients with lower MxA titers.ConclusionThe results suggest that baseline MxA mRNA levels may be useful for predicting whether multiple sclerosis patients will respond or not to interferon-beta treatment.

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Section: Discussionmentioning

confidence: 99%

Baseline MxA mRNA Expression Predicts Interferon Beta Response in Multiple Sclerosis Patients

et al. 2014

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“…Interferons (IFNs) are multifunctional cytokines, which regulate cellular and immune responses as well as antiviral and antitumor activity (12). In addition, IFNs have been generally considered to be anti-proliferative proteins (13,14).…”

Section: Introductionmentioning

confidence: 99%

Poly (I:C) transfection induces mitochondrial-mediated apoptosis in cervical cancer

Chen

Wang

Liu

2016

Molecular Medicine Reports

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Polyinosinic acid:polycytidylic acid, known as poly (I:C), is an analogue of double‑stranded RNA, which exhibits direct antitumor effects against several types of cancer. The present study aimed to evaluate the role of poly (I:C) in the apoptosis of cervical cancer cells. The HeLa human cervical cancer cell line was used in the present study, and cell apoptosis was determined following poly (I:C) transfection. Furthermore, the mRNA levels of interferon (IFN)‑β, the production of reactive oxygen species (ROS), DNA damage, mitochondrial membrane potential (∆Ψm) and the release of cytochrome c, as well as caspase activation, were determined. The effect of IFN‑β on poly (I:C) transfection‑mediated apoptosis was also examined by IFN‑β knockdown. The results showed that poly (I:C) transfection markedly induced HeLa apoptosis, increased the protein levels of pro‑apoptotic B cell lymphoma‑2 (Bcl‑2)‑associated X protein (Bax) and BH3 interacting‑domain death agonist (Bid), and suppressed the protein expression levels of anti‑apoptotic Bcl‑2 and Survivin. However, poly (I:C) transfection increased the mRNA levels of IFN‑β, induced ROS production and increased the levels of phosphorylated γH2A.X, an indicator of DNA damage. In addition, poly (I:C) transfection decreased ∆Ψm, triggered the release of cytochrome c from the mitochondria to the cytosol, and induced caspase‑9 and ‑3 activation. IFN‑β knockdown decreased the poly (I:C)‑induced production of ROS and DNA damage, restored ∆Ψm and cytochrome c release, and suppressed caspase‑9 and ‑3 activation, thereby suppressing poly (I:C)‑mediated apoptosis in the HeLa cells. Together, the results of the present study demonstrated that poly (I:C) transfection induced IFN‑β, contributing to ROS production, DNA damage, and caspase‑9 and ‑3 activation in the HeLa cervical cancer cell line, leading to mitochondrial‑mediated apoptosis.

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“…The higher IFN receptor mRNA levels detected in the pulp tissue may be explained by the various cell types present, as IFN receptors are ubiquitously expressed (Sottini et al . , van Loon et al . ).…”

Section: Discussionmentioning

confidence: 94%