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1.
D. Hesse J. L. Frederiksen N. Koch-Henriksen K. Schreiber E. Stenager A. Heltberg M. Ravnborg K. Bendtzen F. Sellebjerg P. S. Sorensen 《European journal of neurology》2009,16(1):43-47
Background and purpose: Neutralizing antibodies (NAbs) appearing during treatment with Interferon-beta (IFN-β) reduce or abolish bioactivity and therapeutic efficacy. Initial combination therapy with methylprednisolone (MP) may reduce the frequency of NAb positive patients. We hypothesized that MP treatment might also reduce NAb levels and re-establish IFN-β bioactivity in patients already NAb+, who discontinue IFN-β therapy.
Methods: In a 6-month open-label trial, we compared monthly high-dose pulsed MP treatment in 38 Nab positive patients with 35 NAb+, MP-untreated control patients discontinuing any therapy or switching to glatiramer acetate. All patients were NAb+ with an absent in vivo response to IFN-β. NAbs were measured using a cytopathic effect assay and expressed as neutralizing capacity (NC) in percentage of added IFN-β. Bioactivity was expressed as in vivo Myxovirus Resistance Protein A (MxA) mRNA induction in whole blood using real time PCR.
Results: At the end of study, median NAb NC was 92% in both groups. Eight patients (21%) in the MP group and four patients (11%) in the control group had regained an in vivo MxA response to IFN-β ( P = 0.35).
Conclusions: Monthly pulsed MP treatment in NAb positive patients has no beneficial effect on NAb status or IFN-β bioactivity. 相似文献
Methods: In a 6-month open-label trial, we compared monthly high-dose pulsed MP treatment in 38 Nab positive patients with 35 NAb+, MP-untreated control patients discontinuing any therapy or switching to glatiramer acetate. All patients were NAb+ with an absent in vivo response to IFN-β. NAbs were measured using a cytopathic effect assay and expressed as neutralizing capacity (NC) in percentage of added IFN-β. Bioactivity was expressed as in vivo Myxovirus Resistance Protein A (MxA) mRNA induction in whole blood using real time PCR.
Results: At the end of study, median NAb NC was 92% in both groups. Eight patients (21%) in the MP group and four patients (11%) in the control group had regained an in vivo MxA response to IFN-β ( P = 0.35).
Conclusions: Monthly pulsed MP treatment in NAb positive patients has no beneficial effect on NAb status or IFN-β bioactivity. 相似文献
2.
L. F. van der Voort A. Visser D. L. Knol C. B. M. Oudejans C. H. Polman J. Killestein 《European journal of neurology》2009,16(9):1049-1052
Background: Treatment failure to Interferon-beta (IFNβ) in multiple sclerosis (MS) can only partly be explained by anti-IFNβ neutralising antibodies (NAb). Myxovirus resistance protein A (MxA) mRNA, reflecting IFNβ bioactivity, is studied as an alternative biomarker for IFNβ therapy response. Although absent IFNβ bioactivity is associated with NAb and NAb are associated with reduced drug efficacy, the direct relationship between IFNβ bioactivity and clinical disease activity is largely unknown.
Methods: We enrolled 126 consecutive relapsing-remitting MS patients on IFNβ treatment. MxA mRNA expression was assessed 4 h after IFNβ injection. Biological response status was determined after 3 months, by combined measurement of MxA mRNA expression and induction (MxA mRNA expression after/before IFNβ injection). Patients were considered biological non-responders when both MxA mRNA expression and MxA mRNA induction were negative.
Results: Biological non-responders showed a significantly higher annualised relapse rate and smaller proportion relapse-free patients compared with biological responders (relapse rate 0.81 vs. 0.37; proportion relapse free 37% vs. 67%).
Conclusions: Our results suggest that a lack of IFNβ bioactivity is associated with the occurrence of relapses and therefore can be useful as a biomarker for unresponsiveness to IFNβ. 相似文献
Methods: We enrolled 126 consecutive relapsing-remitting MS patients on IFNβ treatment. MxA mRNA expression was assessed 4 h after IFNβ injection. Biological response status was determined after 3 months, by combined measurement of MxA mRNA expression and induction (MxA mRNA expression after/before IFNβ injection). Patients were considered biological non-responders when both MxA mRNA expression and MxA mRNA induction were negative.
Results: Biological non-responders showed a significantly higher annualised relapse rate and smaller proportion relapse-free patients compared with biological responders (relapse rate 0.81 vs. 0.37; proportion relapse free 37% vs. 67%).
Conclusions: Our results suggest that a lack of IFNβ bioactivity is associated with the occurrence of relapses and therefore can be useful as a biomarker for unresponsiveness to IFNβ. 相似文献
3.
Background and purpose: Neutralizing antibody (NAb) titres may vary over time and thereby some patients can either lose or regain therapeutic effect of interferon beta (IFNβ). We assessed NAb titres in a large sample of multiple sclerosis (MS) patients to identify the pattern of fluctuation during 1–3 years.
Methods: Data from IFNβ-treated MS patients who had been tested for NAbs twice ( n = 822) were analysed. NAb titres were compared between the first and the second samples across the critical NAb level of 150 TRU/ml, which we have previously reported to correlate with loss of bioactivity.
Results: Of patients with NAb titres high enough to indicate loss of bioactivity (>150 TRU/ml) in the first analysis 15% showed titres low enough to indicate a regained bioactivity. Conversely, 6% of those without detectable NAbs or NAb titres below the critical level of 150 TRU/ml had shifted to titres above this limit, indicating potential loss of bioactivity. Fluctuation did not differ between IFNβ preparation used, treatment duration or sampling interval.
Conclusion: A first NAb test is prognostic for the NAb status during the coming 1–3 years. Choice of IFNβ preparation had no influence on the chance of reverting to lower levels once NAb titres are high. 相似文献
Methods: Data from IFNβ-treated MS patients who had been tested for NAbs twice ( n = 822) were analysed. NAb titres were compared between the first and the second samples across the critical NAb level of 150 TRU/ml, which we have previously reported to correlate with loss of bioactivity.
Results: Of patients with NAb titres high enough to indicate loss of bioactivity (>150 TRU/ml) in the first analysis 15% showed titres low enough to indicate a regained bioactivity. Conversely, 6% of those without detectable NAbs or NAb titres below the critical level of 150 TRU/ml had shifted to titres above this limit, indicating potential loss of bioactivity. Fluctuation did not differ between IFNβ preparation used, treatment duration or sampling interval.
Conclusion: A first NAb test is prognostic for the NAb status during the coming 1–3 years. Choice of IFNβ preparation had no influence on the chance of reverting to lower levels once NAb titres are high. 相似文献
4.
A. Millonig A. Dressel D. Bahner A. Bitsch T. Bogumil E. Elitok B. Kitze H. Tumani F. Weber C. Gneiss F. Deisenhammer 《European journal of neurology》2008,15(8):822-826
Background and purpose: Interferon beta (IFNβ) preparations have some effect on the progressive phase of multiple sclerosis (MS). This limited effect might be partially because of a certain number of IFNβ non-responders. Myxovirus resistance protein A (MxA) – a marker of IFNβ bioactivity – was correlated with the clinical response during an uncontrolled trial, investigating the safety of IFNβ-1b in primary progressive (PPMS) patients.
Methods: Twenty PPMS were treated with IFNβ-1b (s.c.) for 1 year. Blood samples were taken before and 1, 2, 3, 6, 9, 12, and 15 months after treatment initiation and MxA protein levels were measured. Patients were clinically evaluated by EDSS and the more sensitive Incapacity Status Scale (ISS) and stratified in a stable and a progressing group.
Results: Using ISS criteria, 11 patients remained stable and nine patients progressed during treatment. The mean area under the curve of log MxA levels during treatment were significantly higher in stable than in progressing patients (10.87 vs. 5.99; P = 0.002).
Conclusion: A good biological response to IFNβ might be associated with a better clinical effect of this drug and could be helpful in future clinical studies for early identification of treatment responders. 相似文献
Methods: Twenty PPMS were treated with IFNβ-1b (s.c.) for 1 year. Blood samples were taken before and 1, 2, 3, 6, 9, 12, and 15 months after treatment initiation and MxA protein levels were measured. Patients were clinically evaluated by EDSS and the more sensitive Incapacity Status Scale (ISS) and stratified in a stable and a progressing group.
Results: Using ISS criteria, 11 patients remained stable and nine patients progressed during treatment. The mean area under the curve of log MxA levels during treatment were significantly higher in stable than in progressing patients (10.87 vs. 5.99; P = 0.002).
Conclusion: A good biological response to IFNβ might be associated with a better clinical effect of this drug and could be helpful in future clinical studies for early identification of treatment responders. 相似文献
5.
F. Sellebjerg M. Krakauer D. Hesse L. P. Ryder I. Alsing P. E. H. Jensen N. Koch‐Henriksen A. Svejgaard P. Soelberg Sørensen 《European journal of neurology》2009,16(12):1291-1298
Objective: Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)‐β. NAbs impair the effect of treatment. The biological effect of IFN‐β can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other markers could be more sensitive for evaluating the response to IFN‐β. We used DNA array analysis to identify genes that are strongly induced in blood cells by IFN‐β, and measured their expression in MS patients with different NAb levels. Methods: Gene expression was studied on DNA arrays in untreated patients, in NAb negative patients, and in MS patients with varying NAb levels 9–12 h and 36–48 h after IFN‐β administration. The expression of selected genes was measured by real‐time PCR. NAb levels were assessed by a cytopathic effect assay. Results: Several hundred genes were induced 9–12 h after an injection of IFN‐β. The molecules CXCL10, CCL2 and IFI27 were among the most strongly induced. Gene induction was generally much less pronounced after 36–48 h, but IFI27 remained strongly induced. The strong induction of these molecules and MxA was confirmed by real‐time PCR. Induction of MxA, CCL2, CXCL10 and IFI27 was reduced in patients with low NAb levels and lost in patients with intermediate/high NAb levels. Conclusion: We identify IFI27, CCL2 and CXCL10 as sensitive biomarkers for the response to IFN‐β. The expression of these markers adequately reflects bioactivity of IFN‐ß as documented by the decreased induction in low NAb‐positive patients and the lost induction in patients with moderate/high NAb levels. 相似文献
6.
Many multiple sclerosis (MS) patients treated with IFNbeta develop anti-IFNbeta antibodies, which can interfere with the bioactivity of the injected cytokine, i.e., antibody-mediated decreased bioactivity (ADB). The precise levels of anti-IFNbeta antibodies inducing decreased bioactivity is unknown. We repeatedly used a bioactivity measure, gene expression of MxA or GEM, and correlated bioactivity with measures of binding and neutralizing antibodies. The binding antibody assay was a capture ELISA, and the neutralizing antibody (NAb) assay was a cytopathic effect (CPE) assay. 27% (17/64) of patients repeatedly sampled developed critical ADB. Bioactivity as determined by GEM correlated negatively with NAb titer, and bioactivity that had been lost with the development of NAbs returned if NAb levels diminished. These data reveal that the GEM assay is a useful adjunct in the management of MS patients treated with IFNbeta, and that lost bioactivity returns when anti-IFNbeta antibody levels diminish. 相似文献
7.
M. Comabella J. M. Pradillo M. Fernández J. Río I. Lizasoain E. Julià M. A. Moro J. Sastre-Garriga X. Montalban 《European journal of neurology》2009,16(11):1197-1201
Background: The 15-deoxi delta prostaglandin J2 (15d-PGJ2 ) is a peroxisome proliferator-activated receptor-gamma agonist with potent anti-inflammatory properties. It has been suggested that 15d-PGJ2 may modulate multiple sclerosis (MS).
Methods: Here, we investigated the plasma levels of 15d-PGJ2 by enzyme-linked immunoassay in 28 healthy controls and 140 MS patients [30 patients with primary-progressive MS, 28 patients with secondary-progressive MS, and 82 patients with relapsing-remitting MS (28 patients during clinical remission, 25 patients during relapse, and 29 treated with interferon-beta – IFN-β)].
Results: Levels of 15d-PGJ2 were similar between healthy controls and untreated MS patients with different clinical courses of the disease. Treatment with IFN-β had no effect on levels of 15d-PGJ2 .
Conclusions: Although these findings suggest that 15d-PGJ2 is not involved in the acute or chronic phases of the disease, further studies measuring 15d-PGJ2 in cerebrospinal fluid samples are needed before excluding a role of 15d-PGJ2 in MS. 相似文献
Methods: Here, we investigated the plasma levels of 15d-PGJ
Results: Levels of 15d-PGJ
Conclusions: Although these findings suggest that 15d-PGJ
8.
Malucchi S Gilli F Caldano M Sala A Capobianco M di Sapio A Granieri L Bertolotto A 《Journal of neurology》2011,258(5):895-903
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. 相似文献
9.
Vallittu AM Halminen M Peltoniemi J Ilonen J Julkunen I Salmi A Erälinna JP;Finnish Beta-Interferon Study Group 《Neurology》2002,58(12):1786-1790
BACKGROUND: Neutralizing antibodies (NAb) during interferon-beta (IFNbeta) treatment of MS are associated with reduced clinical and MR efficacy. NAb inhibit the IFN- inducible MxA gene expression and neutralize the capability of IFNbeta to inhibit virus growth in vitro. Presently, there is no clear concept of the biologic importance of IFNbeta antibodies; most of the tests applied for the detection of NAb in previous publications are not widely available, and the results are not fully comparable. METHODS: A 1-year prospective study of the development of binding antibodies (BAb) and NAb and their relationship to IFN-inducible MxA protein levels in peripheral blood leukocytes in 20 IFNbeta-1a-treated patients with relapsing-remitting MS was conducted. RESULTS: In seven of nine NAb-positive patients, IFNbeta-1a was unable to induce MxA protein. BAb were detected in 11 patients, and they preceded or paralleled the development of NAb in all the patients. The titer of NAb correlated positively with BAb titer and negatively with MxA expression level. There was also a weaker but clear correlation between BAb titers and MxA levels. CONCLUSIONS: NAb, in most but not all cases, inhibited the in vivo function of IFNbeta. Analysis of MxA protein in lymphocytes together with analysis of NAb is a promising marker for evaluating the biologic effects of IFNbeta treatment in MS patients. 相似文献
10.
MxA protein production in peripheral blood leukocytes is a valuable marker to evaluate biologic effects of interferon-beta (IFNbeta) therapy in multiple sclerosis (MS) patients. The three IFNbeta preparations available in the treatment of MS differ with respect to antigenicity and biologic activity. We studied prospectively the induction of MxA protein and the development of binding (BAb) and neutralising antibodies (NAb) in nine relapsing-remitting MS (RRMS) patients during one year of intramuscular IFNbeta -1a (Avonex) treatment. Another nine RRMS patient treated with Avonex for 1-3.5 years were also included. The results were compared with our earlier published data of subcutaneous IFNbeta-1a (Rebif). None of these 18 patients developed NAb but three of the long-term patients developed BAb. The baseline MxA protein levels rose but the induction was weaker compared to Rebif. The stimulation index (MxA after/before IFNbeta-1a injection) remained elevated. Weekly intramuscular dosing of IFNbeta-1a provides a sustained effect on lymphocytes but differences in leukocyte stimulation may underlie some of the differences between IFNbeta therapies. 相似文献
11.
D. Matusevicius P. Kivisäkk V. Navikas W.-Z. Tian M. Söderström S. Fredrikson H. Link 《European journal of neurology》1998,5(3):265-275
Inflammatory cell infiltration within the central nervous system (CNS) and upregulation of both pro- and anti-inflammatory cytokines are characteristic for multiple sclerosis (MS). Treatment with interferon-β1b (IFN-β1b) reduces the number and severity of MS relapses. To examine whether treatment with IFN-β1b affects levels of cytokine mRNA expressing blood mononuclear cells (MNC) we employed in-sit hybridization with synthetic oligonucleotide probes to detect and enumerate IFN-γ, TNF-α, IL-10, TGF-β and perforin mRNA expressing cells in MS patients before treatment with IFN-β1b and during tretmetn for 3–6 weeks and for 3–6 monts. Numbers of blood MNC spontaneously expressing TNF-α and IL-10 mRNA were lower after 3–6 months of treatment, while numbers of IFN-γ, TGF-β and perforin mRNA expressing MNC were not affected by treatment. IFN-β1b had no influence on levels of MBP-reactive IFN-γ, TNF-α, TGF-β, IL-10 or perforin mRNA expressing blood MNC determined after 3–6 weeks 3–6 months of treatment. Parallel measurements of plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) revealed elevated levels after 3–6 weeks of treatment and these levels remained higher after 3–6 months of treatment. The results suggest that IFN-β1b treatment upregulates plasma levels of sVCAM-1, but has little effects on numbers of blood MNC expressing mRNA of the pro- and anti-inflammatory cytokines under study. 相似文献
12.
Capra R Sottini A Cordioli C Serana F Chiarini M Caimi L Padovani A Bergamaschi R Imberti L 《Journal of neuroimmunology》2007,189(1-2):102-110
Anti-IFNbeta antibodies are related to IFNbeta bioavailability loss in multiple sclerosis. We investigated the reliability of radioimmunoprecipitation and cytopathic assays in detecting binding (BAbs) and neutralizing (NAbs) antibodies and the correlation of these antibodies to MxA mRNA production. Eleven percent of IFNbeta-treated patients showed a lack of MxA induction, with an inverse correlation between MxA mRNA and the presence of BAbs and NAbs. Some patients had contemporary MxA induction in the presence of high NAb titres, thus calling into question the reliability of cytopathic assay. Since anti-IFNbeta antibodies well correlated with MxA induction loss, MxA assay is an appropriate test to determine IFNbeta bioavailability. 相似文献
13.
Background and purpose: Recombinant interferon-beta is proven as an effective long-term treatment in patients with multiple sclerosis (MS). Unlike in other chronic inflammatory diseases, endogenous synthesis of type I interferons (IFN-alpha and IFN-beta) has not been studied extensively in MS. Mx proteins A and B (MxA and MxB) are intracellular proteins that are induced exclusively by type I IFNs. We investigated the expression of Mx proteins in post-mortem brain tissue of IFN-beta-naïve MS patients as a marker for endogenous synthesis of type I IFNs.
Methods: By employing monoclonal antibodies specific for MxA and MxB positive staining was detectable predominantly in reactive astrocytes within the MS plaques but also in endothelial and ependymal cells as well as in lymphocytic infiltrates.
Results: This is of interest in view of results previously published by our group and others that Mx protein concentrations measured by ELISA increase in blood samples from MS patients after IFN-beta therapy.
Conclusions: In MS, Mx proteins are detectable in plaques suggesting endogenous synthesis of type I IFNs as part of the acute inflammatory process. 相似文献
Methods: By employing monoclonal antibodies specific for MxA and MxB positive staining was detectable predominantly in reactive astrocytes within the MS plaques but also in endothelial and ependymal cells as well as in lymphocytic infiltrates.
Results: This is of interest in view of results previously published by our group and others that Mx protein concentrations measured by ELISA increase in blood samples from MS patients after IFN-beta therapy.
Conclusions: In MS, Mx proteins are detectable in plaques suggesting endogenous synthesis of type I IFNs as part of the acute inflammatory process. 相似文献
14.
Although the occurrence of neutralizing antibodies (NAbs) to interferon (IFN)- β has been acknowledged since the pivotal trials of IFN- β in multiple sclerosis (MS), the effect of these antibodies has for several reasons been debated. The main reason for the controversies has been insufficient knowledge of the fact that clinically relevant NAbs do not appear until 12–18 months after initiation of IFN- β therapy which make studies of 2 years or less unsuited to assess the clinical relevance of NAbs. Further, changes in NAb affinity occur and contribute to increase NAb effects by time.
The present paper reviews our current knowledge of NAbs and stresses the importance of using measurements of NAbs routinely. It is concluded that NAb titres are important for the biological response to IFN- β . Patients with low or intermediate titres may have preserved a full or partial biological response and might still benefit from IFN- β therapy. However, persistent high titres of NAbs indicate an abrogation of the biological response and, hence, absence of therapeutic efficacy, and this observation should lead to a change of therapy. The application of the existing information about NAbs in clinical practice would lead to improved efficacy of IFN- β treatment for the benefit of patients with MS. 相似文献
The present paper reviews our current knowledge of NAbs and stresses the importance of using measurements of NAbs routinely. It is concluded that NAb titres are important for the biological response to IFN- β . Patients with low or intermediate titres may have preserved a full or partial biological response and might still benefit from IFN- β therapy. However, persistent high titres of NAbs indicate an abrogation of the biological response and, hence, absence of therapeutic efficacy, and this observation should lead to a change of therapy. The application of the existing information about NAbs in clinical practice would lead to improved efficacy of IFN- β treatment for the benefit of patients with MS. 相似文献
15.
Objectives – To detect the reactivity pattern of sera from patients with mild and severe Alzheimer's disease (AD) to specific antibodies targeting different epitopes in the primary structure of amyloid-beta (Aβ).
Materials and methods – Sera from patients diagnosed with mild or severe AD were used. The reactivity of sera to monoclonal antibodies recognizing 1–7, 5–10, 9–14 and 17–21 epitopes of Aβ1–40 at 36–42°C was determined by an enzyme-linked immunosorbent assay. Proteinase K digestion of Aβ1–40 was investigated by dot blotting at 36 and 40°C.
Results: – Sera of patients with AD displayed reactivity only with monoclonal antibody recognizing the epitope 17–21 (4G8). The reactivity of sera from patients with severe AD was less than that of sera from patients with mild AD at temperatures 36–41°C, with no difference at 42°C. Patients with severe AD displayed lesser digestion with proteinase K.
Conclusions – Sera derived from patients with AD could react with monoclonal antibodies directed to 17–21 sequences of Aβ1–40 in a temperature-dependent manner. The severity of AD is associated with greater Aβ1–40 aggregation and resistance to proteinase K. The present results may be of value in staging and following up of patients with AD. 相似文献
Materials and methods – Sera from patients diagnosed with mild or severe AD were used. The reactivity of sera to monoclonal antibodies recognizing 1–7, 5–10, 9–14 and 17–21 epitopes of Aβ1–40 at 36–42°C was determined by an enzyme-linked immunosorbent assay. Proteinase K digestion of Aβ1–40 was investigated by dot blotting at 36 and 40°C.
Results: – Sera of patients with AD displayed reactivity only with monoclonal antibody recognizing the epitope 17–21 (4G8). The reactivity of sera from patients with severe AD was less than that of sera from patients with mild AD at temperatures 36–41°C, with no difference at 42°C. Patients with severe AD displayed lesser digestion with proteinase K.
Conclusions – Sera derived from patients with AD could react with monoclonal antibodies directed to 17–21 sequences of Aβ1–40 in a temperature-dependent manner. The severity of AD is associated with greater Aβ1–40 aggregation and resistance to proteinase K. The present results may be of value in staging and following up of patients with AD. 相似文献
16.
M. Garcia‐Montojo M. I. Dominguez‐Mozo V. De Las Heras M. Bartolome A. Garcia‐Martinez R. Arroyo R. Alvarez‐Lafuente 《European journal of neurology》2010,17(3):470-478
Background: The objective of this study was to correlate the detection of neutralizing antibodies (NAbs) by the cytopathic effect (CPE) assay, with the expression of myxovirus resistance protein A (MxA), and the ratio between matrix metalloproteinase 9 (MMP‐9) and its tissular inhibitor (TIMP‐1), in order to evaluate their usefulness as markers of interferon beta (IFN‐beta) bioavailability. Methods: Pairs of blood and serum samples were collected from 50 patients with multiple sclerosis (MS) during 2 years of IFN‐beta treatment. Expression of MxA, MMP‐9 and TIMP‐1 were analysed by quantitative PCR, and NAbs were measured by CPE assay. Results: During the study, 60% of patients presented NAbs. The number of serum samples that were NAbs+ was significantly increased amongst patients with relapses (41/92 vs. 33/108, P = 0.04). With one serum sample and with a NAb titre >100 tenfold reduction unit (TRU), 66.7% of patients with MS suffered from relapses, 41.7% suffered from progression, and 75% was not an optimal clinical responder. We did not find any significant difference in MxA. We found that 62.5% of patients with MS patients whose ratio was increased twofold after 2 years suffered from relapses, 37.5% suffered from progression, and 68.7% was not an optimal clinical responder. Conclusion: The early detection of NAbs by CPE assay and the finding of only one serum sample with a NAb titre >100 TRU seem to be markers of low bioavailability of IFN‐beta, whilst a twofold decrease in the MMP‐9/TIMP‐1 ratio by quantitative PCR assay seems to be a marker of high bioavailability of IFN‐beta. 相似文献
17.
Objectives – Chemokines are involved in migration of inflammatory cells to the central nervous system (CNS) in multiple sclerosis (MS). The aim of this study was the analysis of the impact of MS treatment on CCL5-induced migration of leukocyte subpopulations.
Material and methods – Migration of lymphocytes and monocytes from blood of MS patients treated with methylprednisolone (MP) or mitoxantrone (MTX) was analysed in a chemotaxis chamber.
Results – CCL5-induced migration of lymphocytes from untreated MS patients was significantly increased over controls. The treatment of MS with MP and MTX reduced this chemotaxis. The plasma level of CCL5 was increased in MS patients before treatment and was also significantly decreased in the treatment of MS with MP and MTX.
Conclusions – This observation supports the hypothesis that in MS, chemokine CCL5 may induce migration of leukocytes to the CNS and suggests that treatment of the disease with MP and MTX may reduce this migration. 相似文献
Material and methods – Migration of lymphocytes and monocytes from blood of MS patients treated with methylprednisolone (MP) or mitoxantrone (MTX) was analysed in a chemotaxis chamber.
Results – CCL5-induced migration of lymphocytes from untreated MS patients was significantly increased over controls. The treatment of MS with MP and MTX reduced this chemotaxis. The plasma level of CCL5 was increased in MS patients before treatment and was also significantly decreased in the treatment of MS with MP and MTX.
Conclusions – This observation supports the hypothesis that in MS, chemokine CCL5 may induce migration of leukocytes to the CNS and suggests that treatment of the disease with MP and MTX may reduce this migration. 相似文献
18.
M. Laurà N. A. Gregson K. Smith R. A. C. Hughes 《Neuropathology and applied neurobiology》2002,28(2):169-169
Introduction: Amyloid β (Aβ) protein, a 38–42 amino acid peptide is the major component of senile plaques in Alzheimer's disease and has been suggested to exert its toxic effects via the direct and indirect production of reactive oxygen species.
Materials and methods: We have investigated the role of reactive oxygen species in the toxic actions of Aβ on a human neuronal cell line SHSY-5Y, using the MTT assay for cellular viability and comparing the toxicity of Aβ with that of H2 O2 .
Results: The neurotoxic fragment of Aβ protein, Aβ25–35 , had clear concentration- and time-dependent toxic effects on SHSY-5Y cells. The ability of antioxidants to reverse these toxic effects of 10 µ m Aβ25–35 or 200 µ m H2 O2 were tested. Vitamin E (10–100 µ m ) did not affect either Aβ or H2 O2 . Trolox, a vitamin E analogue (5–200 µ m ) had protective effects on H2 O2 ‐induced cell death but was ineffective in preventing the cell death induced by Aβ. Vitamin C (10–1000 µ m ) partially reversed H2 O2 -induced toxicity but had no protective action when cells were exposed to Aβ.
Discussion: These results indicate that the mechanisms by which Aβ and H2 O2 exert their toxic effects are different and suggest that in this experimental system, formation of reactive oxygen species do not have major role in Aβ-induced cell death. 相似文献
Materials and methods: We have investigated the role of reactive oxygen species in the toxic actions of Aβ on a human neuronal cell line SHSY-5Y, using the MTT assay for cellular viability and comparing the toxicity of Aβ with that of H
Results: The neurotoxic fragment of Aβ protein, Aβ
Discussion: These results indicate that the mechanisms by which Aβ and H
19.
Objectives – We aimed to evaluate the quality of life among young ischaemic stroke (IS) patients at long-term follow-up by comparing them with multiple sclerosis (MS) patients with secondary progressive course. The mean age at stroke onset was 41.6 years.
Methods – Nottingham Health Profile scores were obtained from 191 IS patients 6 years (mean) after the index stroke, from 337 MS patients 5 years (mean) after the onset of the secondary progressive course and from 216 controls.
Results – The mean age of IS patients was 47.8 years and MS patients 44.5 years at follow-up. The MS patients as a group had worse subscores than the IS patients. When adjusting for physical mobility, complaints of fatigue ( P = 0.012) were more frequent among MS patients, whereas pain ( P < 0.001) and sleep ( P = 0.007) disturbances were more frequent among IS patients.
Conclusion – The comparison of IS and MS patients highlights the importance of pain and sleep disturbances among IS patients when adjusting for physical mobility. 相似文献
Methods – Nottingham Health Profile scores were obtained from 191 IS patients 6 years (mean) after the index stroke, from 337 MS patients 5 years (mean) after the onset of the secondary progressive course and from 216 controls.
Results – The mean age of IS patients was 47.8 years and MS patients 44.5 years at follow-up. The MS patients as a group had worse subscores than the IS patients. When adjusting for physical mobility, complaints of fatigue ( P = 0.012) were more frequent among MS patients, whereas pain ( P < 0.001) and sleep ( P = 0.007) disturbances were more frequent among IS patients.
Conclusion – The comparison of IS and MS patients highlights the importance of pain and sleep disturbances among IS patients when adjusting for physical mobility. 相似文献
20.
X.-J. Cheng Q. Cheng L.-Z. Xu H.-Q. Zhao Z. Zhao W. Wang G.-X. Jiang S. Fredrikson 《Acta neurologica Scandinavica》2010,121(1):24-29
Objective – To evaluate the discharge diagnosis of demyelinating diseases in the central nervous system (CNS) and analyze the predictive value of the new diagnostic criteria in Suzhou, China.
Materials and methods – We collected clinical information and data of laboratory examinations for all cases with a diagnosis of various demyelinating diseases in the CNS. All data were reviewed individually by four senior neurologists, and a diagnosis was finally given to each patient according to the McDonald criteria and the Poser criteria for multiple sclerosis (MS).
Results – In the analysis, 176 patients with a diagnosis of demyelinating diseases in the CNS at discharge were included. In 82 patients with a diagnosis of MS at discharge, the MS diagnosis was confirmed for 74 patients according to the McDonald criteria for MS, and the positive predictive value for the discharge diagnosis of MS was 90.2% (74/82). According to the Poser criteria, 61 patients were diagnosed as MS. The consistency of the two diagnostic criteria for MS was 78.4%, based on the results of the evaluation.
Conclusions – Under-diagnosis of MS could be one of the explanations for the low prevalence of MS in China. Compared to the Poser criteria, the McDonald criteria had a higher sensitivity for the diagnosis of MS. 相似文献
Materials and methods – We collected clinical information and data of laboratory examinations for all cases with a diagnosis of various demyelinating diseases in the CNS. All data were reviewed individually by four senior neurologists, and a diagnosis was finally given to each patient according to the McDonald criteria and the Poser criteria for multiple sclerosis (MS).
Results – In the analysis, 176 patients with a diagnosis of demyelinating diseases in the CNS at discharge were included. In 82 patients with a diagnosis of MS at discharge, the MS diagnosis was confirmed for 74 patients according to the McDonald criteria for MS, and the positive predictive value for the discharge diagnosis of MS was 90.2% (74/82). According to the Poser criteria, 61 patients were diagnosed as MS. The consistency of the two diagnostic criteria for MS was 78.4%, based on the results of the evaluation.
Conclusions – Under-diagnosis of MS could be one of the explanations for the low prevalence of MS in China. Compared to the Poser criteria, the McDonald criteria had a higher sensitivity for the diagnosis of MS. 相似文献