Interferon Beta Therapy In Patients Research Articles

Assessment of Thyroid Functions in Multiple Sclerosis Patients Treated with Disease Modifying Therapies

Background:
 Multiple sclerosis is a chronic disease believed to be the result of autoimmune disorders of the central nervous system, characterised by inflammation, demyelination, and axonal transection, affecting primarily young adults. Disease modifying therapies have become widely used, and the rapid development of these drugs highlighted the need to update our knowledge on their short- and long-term safety profile.
 Objective:
 The study aim is to evaluate the impact of disease-modifying treatments on thyroid functions and thyroid autoantibodies with subsequent effects on the outcome of the disease.
 Materials and Methods:
 A retro prospective study enrolled 45 patients who were registered and diagnosed in the Multiple Sclerosis Clinic according to the revised McDonald criteria (2017). Blood samples for thyroid functions and thyroid autoantibody tests were taken before, 3 months and after 6 months from the start of disease modifying therapy. The Expanded Disability Status Scale was used to assess the severity of the disease before and after 6 months of receiving treatment.
 Results:
 45 patients with the mean age of 33.3 years, a standard deviation (SD) of ± 9.5 years were enrolled in this study. (64.4%) patients’ age was between 20 - 39 years.
 The mean free T3 decreased significantly, while the mean anti-TPO and anti-TG increased after three months compared to its baseline level.
 After six months of treatment, the mean free T4 decreased significantly, while the mean TSH increased compared to its baseline level. There were no statistically significant correlations between the baseline (EDSS) score and after 6 months of therapy.
 Conclusion
 Thyroid hormone dysfunction and thyroid autoimmune antibody levels that changed in response to interferon beta therapy in patients with multiple sclerosis may be temporary and not associated with poor outcomes.

MicroRNA-29b variants and MxA expression change during interferon beta therapy in patients with relapsing-remitting multiple sclerosis

BackgroundMultiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by immune-mediated demyelination and axonal injury. Myelin-reactive IFN-γ-producing Th1 cells has been shown to play an important role in the development of MS. MicroRNAs (miRNAs) are a new class of small non-coding RNA molecules about 22 nucleotides long which regulate gene expression post-transcriptionally by binding to 3′ UTR of their mRNA targets, and resulting in degradation or transcriptional repression of the targeted mRNA. Accumulating evidence supports that miRNA dysregulation is linked to the pathogenesis of autoimmune diseases that include MS. miR-29b expression has been shown to be upregulated in memory CD4+T cells from relapsing-remitting MS (RR-MS) patients, which may reflect chronic Th1 inflammation. Interferon beta (IFN-β) benefits patients with MS and reduces symptoms of the RR-MS. MxA is induced by type I interferon and predicts IFN-β response in MS patients. The aim of this study was to evaluate miR-29b variants and MxA expression and serum IFN-γ level in responders and non-responders to IFN-β treatment. MethodsA total of 70 IFN-β treated RR-MS patients including 35 responders and 35 non-responders were enrolled. We analyzed the expression level of miR-29b variants and MxA using the peripheral blood of MS patients treated with IFN-β for more than one year. Real-time RT-PCR was performed to analyze miR-29b variants and MxA expression one year after initiation of IFN-β therapy. Serum cytokine level was measured by ELISA. ResultsThe results indicated that the expression level of miR-29b-3p changed related to IFN-β response. Moreover, miR-29b-5p was downregulated under IFN-β treatment in responders versus non-responders. MxA level was significantly decreased in the responders. There was no change in IFN-γ level following treatment with IFN-β in the MS patients. ConclusionsOur results might provide fundamentals for the development of new markers of the biological effects of IFN-β therapy.

Non-adherence to interferon-beta therapy in Swedish patients with multiple sclerosis

To explore the occurrence and reasons for stopping, switching or continuing first prescribed interferon-beta therapy in patients with multiple sclerosis in Sweden, with respect to demographic, clinical and/or therapy-related factors. A retrospective study reviewing the medical charts of 259 patients with multiple sclerosis, comparing patients continuing therapy for at least 3 years with those switching or stopping therapy. Sixty 9% stopped (15%), or switched (54%), interferon-beta therapy within 3 years. Stoppers had longer disease duration before starting therapy (P = 0.002), less frequently relapsing-remitting multiple sclerosis (P = 0.046), and more often Expanded Disability Status Scale scores 6-9.5 (P = 0.045) compared to Switchers. The most common reasons for switching/stopping therapy were perceived lack of effect and side-effects. Adherence to initial immune-modulating therapy is low; identification of patients at higher risk of stopping therapy and provision of adequate support are essential.

Clinical significance of antibodies to interferon beta therapy in patients with relapsing–remitting multiple sclerosis

Clinical significance of antibodies to interferon beta therapy in patients with relapsing–remitting multiple sclerosis

Enhancement of Chemokine Expression by Interferon Beta Therapy in Patients With Multiple Sclerosis

Interferon beta has been approved for the treatment of multiple sclerosis (MS). It is believed that immunomodulatory rather than antiviral activity of interferon beta is responsible for disease amelioration. The impact of interferon beta on the chemoattraction of immune cells has not been fully addressed. To address the influence of interferon beta on the expression of chemokines and their receptors in a standardized setting. The expression of 14 chemokines and 14 chemokine receptor genes was determined by quantitative real-time polymerase chain reaction from fresh blood samples. Outpatient units in Germany. Patients Untreated and interferon beta-treated patients with MS who tested positive and negative for neutralizing antibodies (NABs) were recruited from August 24, 2006, through December 15, 2006, for the initial study and from March 12, 2007, through April 2, 2007, for the validation study. Gene expression and serum chemokine protein levels. CCL1, CCL2, CCL7, CXCL10, CXCL11, and CCR1 gene expression was strongly upregulated in interferon beta-treated, NAB-negative MS patients. In contrast, gene expression in interferon beta-treated, NAB-positive MS patients did not differ from untreated control donor individuals. Antibody titers inversely correlated with chemokine and chemokine receptor gene expression. Accordingly, serum chemokine protein levels of interferon beta-treated, NAB-negative MS patients were significantly higher than in untreated or interferon beta-treated, NAB-positive MS patients. We demonstrate that interferon beta strongly upregulates a set of chemokines and CCR1 in peripheral immune cells. The peripheral upregulation of these chemokines may reduce the chemoattraction of immune cells to the central nervous system and thus add to the therapeutic effects of interferon beta.

Genome-wide Scan of 500 000 Single-Nucleotide Polymorphisms Among Responders and Nonresponders to Interferon Beta Therapy in Multiple Sclerosis

Interferon beta is 1 of 2 first-line treatments for relapsing-remitting multiple sclerosis (MS). However, not all patients respond to interferon beta therapy, and to date there is a lack of surrogate markers that reliably correlate with responsiveness to interferon beta therapy in MS. To identify allelic variants that influence response to interferon beta therapy in patients with MS. Genome-wide scan. Academic research. Patients Two hundred patients having relapsing-remitting MS treated with interferon beta and having a follow-up period of at least 2 years were classified as responders or nonresponders to treatment based on stringent clinical criteria. In the first phase of the study, a pooling-based genome-wide association study of 428 867 single-nucleotide polymorphisms (SNPs) was performed in 53 responders and 53 nonresponders to interferon beta therapy. After applying several selection criteria, 383 SNPs were individually genotyped in an independent validation cohort of 49 responders and 45 nonresponders to interferon beta therapy using a different genotyping platform. Eighteen SNPs had uncorrected P < .05 associated with interferon beta responder status in the validation cohort. Of these, 7 SNPs were located in genes that code for alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid-type glutamate receptor GRIA3, type 1 interferon-related proteins ADAR and IFNAR2, cell cycle-dependent protein CIT, zinc finger proteins ZFAT and ZFHX4, and guanosine triphosphatase-activating protein STARD13. This study supports an underlying polygenic response to interferon beta treatment in MS and highlights the importance of the glutamatergic system in patient response to interferon beta therapy.

Glypican 5 is an interferon-beta response gene: a replication study

Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Interferon-beta is the most usual therapy in relapsing-remiting MS. However, approximately 50% of the treated patients do not respond adequately. Very recently, a genome-wide association study on interferon-beta pharmacogenetics has described polymorphisms at several genes that are associated with response to this treatment. Our aim is to replicate the results obtained at the two loci most strongly implicated in the response to interferon-beta treatment, HAPLN1 and GPC5. Patients and methods We performed a case–control study, analyzing 199 patients with MS treated with interferon-beta for at least 2 years and at least two documented relapses over the 2 years, previous to treatment onset. Responders had neither relapses nor increase in expanded disability status scale (EDSS) over the 2-year follow-up period, whereas nonresponders had at least two relapses or an increase in EDSS of at least 1 point. We studied three single-nucleotide polymorphisms (SNPs) in the GPC5 locus and three SNPs in the HAPLN1 locus by TaqMan technology. Allelic frequencies between responders and nonresponders were compared by a chi-square test. Results An association was found between GPC5 polymorphisms and the response to interferon-beta therapy in patients with MS, in agreement with earlier data (responder vs nonresponder patients: rs10492503, P = 0.0005). The other locus studied (HAPLN1) did not show association with treatment response to interferon-beta (all SNPs P > 0.05). Conclusions We confirm the association of polymorphisms within GPC5 with response to interferon-beta therapy in patients with MS.

Correlation Between Depression and Interferon-Beta Therapy in Patients with Multiple Sclerosis: A Systematic Review

Introduction:Depression is the most frequent psychiatric disorder encountered in patients with Multiple Sclerosis (MS), with a life-time prevalence of approximately 50%. INF-beta (INF-β) shows beneficial effect on the course of MS. Although it has been suggested that interferons may be associated to depression, the validity and the nature of this relationship remain unclear regarding INF-β. The objective of this study is to review the scientific literature in order to elucidate the relationship between depression and INF-β therapy.Methods:This systematic review was based on Medline, Embase and, PsycLIT literature searches (through January 2005), supplemented by bibliographical citations in identified papers.Results:The majority of studies ruled out a correlation between INF-β1a/1b and depression in MS patients. However, patients with a recent history of depression may be at higher risk for depression particularly in the early phase of treatment (first 6 months), even if they are not depressed at the initiation of medication. There is an association between depressive symptoms and discontinuation of INF therapy but INF-β does not seem to be associated with suicide attempts. Treating patient-reported depression increases adherence to treatment.Conclusions:Clinicians should not refrain from including patients with MS in INF-β treatment programs, even those with depression in the past or at the present time. Screening, monitoring, and early antidepressant treatment is necessary to optimize IFN therapy for the majority of patients with MS.

HLA-A2-restricted cytotoxic T lymphocyte activity during interferon beta therapy in patients with chronic hepatitis C.

Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes (CTL) may contribute to viral clearance and liver cell injury in patients with chronic hepatitis C. In the present study, we attempted to determine the serial HCV-specific CTL activity during interferon-beta (IFN-beta) therapy in patients with chronic hepatitis C and whether there is any relationship between the CTL response and clinical response to IFN-beta therapy. Eight HLA-A2-positive patients with chronic hepatitis C were treated initially with 6 million U/ml of IFN-beta every day for 8 weeks and then 3 times weekly for the subsequent 16 weeks. Peripheral blood mononuclear cells (PBMC) were collected before the start, 4 weeks after the start, and after the end of IFN treatment and were stimulated with 2 peptides corresponding to core sequences, which were previously reported to have an HLA-A2 restricted-CTL epitopes. Cytolytic activity was determined by a standard 51Cr-release assay using allogenic HLA-matched EBV-transformed B lymphoblastoid cell lines (B-LCL). HCV-specific CTL responses were detected in 2 of the 8 patients before treatment with IFN-beta. One of 2 patients was not observed HCV-specific CTL responses after 4 weeks of IFN-beta treatment, however these two patients showed CTL responses at the end of IFN-beta treatment, and finally HCV-RNA was negative. In addition, HCV-specific CTL responses were observed in 4 patients after 4 weeks of IFN-beta treatment. Three of these 4 patients showed CTL responses only at 4 weeks after IFN-beta treatment. However, there were no differences between clinical parameters or between IFN efficacy in HCV specific CTL response-positive (n = 4) and -negative (n = 4) patients at 4 weeks after the start of IFN-beta treatment. These findings suggest that there are few relations between peripheral HCV-specific CTL response and clinical response to IFN therapy in patients with chronic hepatitis C, although IFN enhances the host immune response against HCV synergistically with antiviral activities.