Expression of interferon type-I receptor isoforms, clinical response and development of neutralizing antibodies in multiple sclerosis patients – results of a prospective study

2016 ◽  
Vol 40 (2) ◽  
Author(s):  
Angelika Bauer ◽  
Dagmar Rudzki ◽  
Michael Auer ◽  
Harald Hegen ◽  
Florian Deisenhammer
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Response ◽  
Neutralizing Antibodies ◽  
Type I ◽  
Expression Levels ◽  
Clinical Endpoints ◽  
Relapsing Remitting ◽  
Pre Treatment ◽  
Multiple Sclerosis Patients ◽  
A Prospective Study

AbstractOne of the first line treatments for relapsing-remitting multiple sclerosis (RRMS) is interferon-β (IFNb), a cytokine with immune-modulatory effects. There is a high degree of variability in the response to the drug which is, among other factors, due to the presence of neutralizing antibodies (NABs) occurring late during therapy.The objective of this study was to determine whether the response to IFNb therapy and NAB development can be predicted based on the expression levels of the type-I interferon receptors IFNAR1, IFNAR2a, IFNAR2b, and IFNAR2c before start of treatment. The IFNAR expression levels in 163 samples of patients with relapsing-remitting MS were measured by real-time polymerase chain reaction (PCR).Pre-treatment IFNAR2c expression levels were somewhat lower in patients who developed NAB during treatment compared to NAB-negative patients. No significant differences in the expression levels of other IFNAR subtypes and isotypes were found. Baseline IFNAR levels were not predictive of the clinical response after 2 years.Overall, there was a small, non-significant effect of IFNAR2c baseline levels on NAB development but no relation to clinical endpoints. Lower expression of IFNAR2c receptors could lead to higher IFNb levels inducing a higher rate of antibody response.

Pupillary response to sparse multifocal stimuli in multiple sclerosis patients

2013 ◽  
Vol 20 (7) ◽  
pp. 854-861 ◽  
Author(s):  
EN Ali ◽  
T Maddess ◽  
AC James ◽  
C Voicu ◽  
CJ Lueck
Keyword(s):  
Multiple Sclerosis ◽  
Pupillary Response ◽  
Time To Peak ◽  
Relapsing Remitting ◽  
Percentage Area ◽  
History Of ◽  
Diagnostic Power ◽  
Multiple Sclerosis Patients ◽  
A Prospective Study ◽  
Delayed Time

Objectives: The objective of this paper is to investigate the pattern of abnormalities and establish the diagnostic power of multifocal objective pupil perimetry (mfPOP) in multiple sclerosis (MS). Methods: A prospective study enrolling 35 normal (47.9 ± 16.8 years, 22 females) and 85 MS subjects (49.8 ± 11.3 years, 62 females; 72 relapsing–remitting (RR), and 13 primary or secondary progressives (PorS)). EDSS scores for the RR and PorS groups were 3.53 ± 1.04 (mean ± SD), and 5.9 ± 1.43, respectively. mfPOP responses were obtained from 44 regions/visual field. Each region was analysed according to response time-to-peak and standardised amplitude (AmpStd). Predictive power was measured by percentage area under the receiver operator curve (%AUC). Results: mfPOP responses showed a significant reduction of 0.69 ± 0.04 dB (mean ± SE) in AmpStd and significantly delayed time-to-peak of 25.95 ± 0.89 ms (mean ± SE) in MS subjects compared to control subjects ( p<0.001). %AUC was greater for time-to-peak than AmpStd both for RR and PorS patients. Diagnostic power followed the EDSS scores but not a history of optic neuritis. Conclusions: mfPOP is well tolerated and potentially has a role in the diagnosis and assessment of patients with MS.

Polymorphisms of innate pattern recognition receptors, response to interferon-beta and development of neutralizing antibodies in multiple sclerosis patients

2010 ◽  
Vol 16 (8) ◽  
pp. 942-949 ◽  
Author(s):  
Christian Enevold ◽  
Annette B Oturai ◽  
Per Soelberg Sørensen ◽  
Lars P Ryder ◽  
Nils Koch-Henriksen ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pattern Recognition ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Pattern Recognition Receptors ◽  
Single Nucleotide ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Interferon-beta therapy of patients with relapsing—remitting multiple sclerosis involves repeated ‘immunizations’ with exogenous protein solutions. Innate pattern recognition receptors play an important role in immune responses towards foreign substances and may thus be related to treatment outcome. Objective: To determine the genotypes at 42 single nucleotide polymorphism loci in selected pattern recognition receptors for 567 prospectively followed relapsing—remitting multiple sclerosis patients treated with recombinant interferon-beta, and test for relationships to several outcome parameters, including formation of interferon-beta neutralizing antibodies. Results: The results suggest an association between the rs5743810 polymorphism (Ser249Pro) of TLR6 and development of neutralizing antibodies after 24 months of therapy in males ( p = 0.00002), but not in females ( p = 0.2). This association survived crude Bonferroni correction ( pcorrected = 0.02). Additional associations were observed in carriers of the TLR2-rs5743708 and NOD2-rs3135499 SNPs (time to relapse), the TLR7-rs179008 and NOD1-rs2075820 SNPs (time to disease progression) and the TLR4-rs7873784, TLR9-rs5743836, and NOD2-rs2066842 SNPs (frequency of neutralizing antibodies development). All of these, however, failed to survive correction for multiple testing. There were no significant differences between interferon-beta responders and non-responders for any of the investigated single nucleotide polymorphisms. Conclusions: The rs5743810 polymorphism of TLR6 may be involved in development of anti-interferon-beta antibodies in males, although further studies are required to firmly establish this.

scholarly journals Methylprednisolone stimulated gene expression (GILZ, MCL-1) and basal cortisol levels in multiple sclerosis patients in relapse are associated with clinical response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Eleftheria Evangelopoulos ◽  
Narjes Nasiri-Ansari ◽  
Eva Kassi ◽  
Anna Papadopoulou ◽  
Dimitrios Stergios Evangelopoulos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Clinical Response ◽  
Suppressive Effect ◽  
Basal Cortisol ◽  
Vitamin D Levels ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Multiple Sclerosis Patients ◽  
Inflammatory Molecules

AbstractGlucocorticoids (GCs) are the main treatment of relapse in multiple sclerosis (MS). Decreased sensitivity to GCs in MS patients has been associated with lack of the suppressive effect of GCs on inflammatory molecules as well as increased resistance to apoptosis. We investigated GC-sensitivity by measuring the effect of intravenous methylprednisolone (IVMP) treatment on transactivation of anti-inflammatory and apoptotic genes (GILZ, MCL-1 and NOXA respectively), in accordance to clinical outcome. Thirty nine MS patients were studied: 15 with clinically isolated syndrome (CIS), 12 with relapsing remitting (RRMS) and 12 with secondary progressive (SPMS) under relapse. Patients underwent treatment with IVMP for 5 days. Blood was drawn before IVMP treatment on day 1 and 1 h after IVMP treatment on days 1 and 5. GIlZ, MCL-1 and NOXA were determined by qPCR. The Expanded Disability Status was evaluated and patients were divided according to their clinical response to IVMP. GILZ and MCL-1 gene expression were significantly higher following first IVMP treatment in responders, compared to non-responders. Furthermore, serum basal cortisol and 1,25-OH Vitamin D levels were significantly higher in clinical-responders as compared to non-clinical responders. Our findings suggest that the differential GILZ and MCL-1 gene expression between clinical-responders and non-clinical responders may implicate the importance of GILZ and MCL-1 as possible markers for predicting glucocorticoid sensitivity and response to GC-therapy in MS patients following first IVMP injection.

Withdrawal of fingolimod treatment for relapsing–remitting multiple sclerosis: report of six cases

2012 ◽  
Vol 18 (11) ◽  
pp. 1636-1639 ◽  
Author(s):  
Bahia Hakiki ◽  
Emilio Portaccio ◽  
Marta Giannini ◽  
Lorenzo Razzolini ◽  
Luisa Pastò ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Laboratory ◽  
Management Strategies ◽  
Effective Management ◽  
Imaging Data ◽  
Relapsing Remitting ◽  
Pre Treatment ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Systematic Collection

The objective of this article is to report our experience on fingolimod suspension in multiple sclerosis patients. We evaluated clinical and magnetic resonance (MR) outcomes in six patients after fingolimod discontinuation. Within three months from fingolimod suspension, five subjects returned to pre-treatment disease activity; one patient, however, exhibited a clear rebound of clinical and MR activity. Our findings suggest that clinical and MR outcomes after fingolimod suspension can vary among patients. Systematic collection of clinical, laboratory and imaging data is highly advisable to identify subjects who are at higher risk of rebound and to define effective management strategies in these subjects.

Neutralizing antibody (NAb) assays in multiple sclerosis patients receiving interferon-β therapy

2007 ◽  
Vol 13 (1_suppl) ◽  
pp. 44-48 ◽  
Author(s):  
Florian Deisenhammer
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Diagnostic Value ◽  
Diagnostic Methods ◽  
Type I ◽  
Interferon Β ◽  
First Line Therapy ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Interferon-β (IFN-β), a type I cytokine, is first-line therapy for relapsing-remitting multiple sclerosis (RRMS), a progressive neurological disease that can result in severe disability. As with all protein-based therapies, treatment with IFN-β can result in the development of neutralizing antibodies (NAbs), which has been shown to reduce the efficacy of the regimen. Recently, assays that evaluate patients for the presence of NAbs have received increased attention as a potentially valuable diagnostic tool in assessing the therapeutic effect of a chosen IFN-β regimen. However, despite the clinical desire to consistently monitor NAb levels in these patients, no standardized NAb assay has yet been identified. A lack of method standardization can lead to confusion when comparing NAb results over time and reduces the overall diagnostic value of assessing NAb status. This review will offer a summary of current NAb diagnostic methods and the factors that limit their consistency and practicality in the clinical setting. Alternatives to current methods for assessing NAb status will also be briefly discussed. Multiple Sclerosis 2007; 13: S44—S48. http://msj.sagepub.com

scholarly journals The Cost of Relapsing-Remitting Multiple Sclerosis Patients Who Develop Neutralizing Antibodies during Interferon Beta Therapy

PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0159214 ◽  
Author(s):  
Damiano Paolicelli ◽  
Sergio Iannazzo ◽  
Laura Santoni ◽  
Antonio Iaffaldano ◽  
Valentina Di Lecce ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neutralizing Antibodies ◽  
Interferon Beta ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
The Cost ◽  
Relapsing Remitting Multiple Sclerosis

Reduced effectiveness of long-term interferon-β treatment on relapses in neutralizing antibody-positive multiple sclerosis patients: a Canadian multiple sclerosis clinic-based study

2007 ◽  
Vol 13 (9) ◽  
pp. 1127-1137 ◽  
Author(s):  
C. Boz ◽  
J. Oger ◽  
E. Gibbs ◽  
S.E. Grossberg ◽  
Keyword(s):  
Multiple Sclerosis ◽  
Relapse Rate ◽  
Neutralizing Antibodies ◽  
Clinical Effect ◽  
Neutralizing Antibody ◽  
Interferon Β ◽  
Pre Treatment ◽  
Multiple Sclerosis Patients ◽  
Relapse Rates

Multiple sclerosis (MS) patients treated with interferon-beta (IFN-β) often form anti-IFN-β antibodies accompanied by a reduction in IFN-β bioavailability. The clinical effect of these antibodies remains controversial. MS patients in British Columbia, Canada, must be diagnosed and evaluated annually by neurologists in an MS clinic in order to be reimbursed for their IFN-β prescriptions. We have identified at the UBC MS clinic a cohort of 262 patients, each having been treated with a single IFN-β preparation more than three years, some for nearly a decade. Of 119 patients treated with Betaseron® (IFN-β1b), 18 (15.1%) were neutralizing antibody positive (NAb+) at the time of the study, whereas of 131 treated with subcutaneous Rebif® (IFN-β1a SC), 16 (12.2%) were NAb+, but none of 12 treated with intramuscular Avonex ® (IFN-β1a) had detectable neutralizing antibodies. During the first two years of treatment, the relapse rate was significantly reduced from pre-treatment rates ( P < 0.001) and appeared to be unaffected by the subsequent NAb status. However, the relapse rates in the NAb+ patients were significantly greater than in the NAb— patients during years 3 ( P < 0.010) and 4 ( P < 0.027). Betaseron ®-treated NAb+ patients tended to have more relapses than NAb — patients during year 3 and this almost reached significance ( P = 0.056) but their relapse rate did not differ in year 4 and later. In contrast, Rebif ®-treated NAb+ patients tended to have more relapses in year 3 than Rebif ® -treated NAb — patients ( P = 0.074), but in year 4 they clearly ( P = 0.009) had more relapses than Rebif ®-treated NAb — patients. There was no convincing effect on progression of disability in any group. Multiple Sclerosis 2007; 13: 1127—1137. http://msj.sagepub.com

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