Comparative study of four different assays for the detection of binding antibodies against interferon-β

2008 ◽  
Vol 14 (6) ◽  
pp. 830-836 ◽  
Author(s):  
C Gneiss ◽  
M Brugger ◽  
A Millonig ◽  
A Fogdell-Hahn ◽  
D Rudzki ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Area Under The Curve ◽  
Neutralizing Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Operating Characteristics ◽  
Interferon Β ◽  
Characteristics Analysis ◽  
Direct Binding ◽  
Immuno Assay ◽  
Multiple Sclerosis Patients

Background Binding antibodies (BAB) against interferon-β (IFNβ) are often determined as screening assays before performing an expensive and elaborate neutralizing antibody (NAB) test. Methods In this study, we compared four BAB tests, a western blot (WB), a direct binding enzyme-linked immunosorbent assay (ELISA) (dELISA), a capture ELISA (cELISA), and a commercial enzyme immuno-assay (EIA) in 325 multiple sclerosis patients with and without neutralizing antibodies to evaluate the sensitivity and specificity to detect NAB by receiver operating characteristics analysis. Results The area under the curve (AUC) values were 0.907 for the dELISA, 0.925 for the cELISA, and 0.776 for the EIA ( P < 0.0001 for all). At a sensitivity of 95%, the specificity was approximately 30% in the dELISA, 55% in the cELISA, and 13% in the EIA. The WB as a qualitative BAB detection method had a given sensitivity of 97% and a specificity of 55%. There was a strong and significant correlation between high NAB titers (>500 neutralizing units [NU]) and titers obtained by all quantitative BAB assays. However, low to medium NAB titers (20–500 NU) did not significantly correlate with BAB titers. Conclusion We conclude that the cELISA seems to be most suitable for NAB screening, but BAB titers cannot reliably predict NAB titers.

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

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

Abstract WP5: Outcomes Are Not Different Between Patients With Intermediate and High Dwi-aspects After Stent-retriever Thrombectomy

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Woong Yoon ◽  
Seul Kee Kim ◽  
Tae Wook Heo ◽  
Byung Hyun Baek ◽  
Jaechan Park
Keyword(s):  
Functional Outcome ◽  
Time Window ◽  
Multivariate Logistic Regression Analysis ◽  
Area Under The Curve ◽  
Stent Retriever ◽  
Operating Characteristics ◽  
Anterior Circulation ◽  
Good Outcome ◽  
Characteristics Analysis ◽  
The Impact

Introduction: Few studies have investigated the association between pretreatment DWI-ASPECTS and functional outcome after stent-retriever thrombectomy in patients with acute anterior circulation stroke. Hypothesis: Patients with acute stroke and DWI-ASPECTS <7 might have a similar chance of a good outcome compared to those with a higher DWI-ASPECTS, if they are treated with a stent-retriever thrombectomy in a short time window. However, this hypothesis has not been tested. Thus, this study aimed to investigate the impact of DWI-ASPECTS on functional outcome in patients with acute anterior circulation stroke who received a stent-retriever thrombectomy. Methods: We retrospectively analyzed the clinical and DWI data from 171 patients with acute anterior circulation stroke who were treated with stent-retriever thrombectomy within 6 hours of symptom onset. The DWI-ASPECTS was assessed by two readers. A good outcome was defined as a modified Rankin Scale score of 0-2 at 3 months. Results: The median DWI-ASPECTS was 7 (interquartile range, 6-8). Receiver operating characteristics analysis revealed an ASPECTS ≥ 7 was the optimal cut-off to predict a good outcome at 3 months (area under the curve=0.57; sensitivity, 75.3%; specificity, 34.4%). The rates of good outcome, symptomatic hemorrhage, and mortality were not different between high DWI-ASPECTS (scores of 7-10) and intermediate (scores of 4-6) groups. In patients with an intermediate DWI-ASPECTS, good outcome was achieved in 46.5% (20/43) of patients with successful revascularization (modified TICI 2b or 3), whereas no patients without successful revascularization had a good outcome ( P =0.016). In multivariate logistic regression analysis, independent predictors of good outcome were age and successful revascularization. Conclusions: Our study suggested that treatment outcomes were not different between patients with a high DWI-ASPECTS and those with an intermediate DWI-ASPECTS who underwent stent-retriever thrombectomy for acute anterior circulation stroke. Thus, patients with an intermediate DWI-ASPECTS otherwise eligible for endovascular therapy should not be excluded for stent-retriever thrombectomy or stroke trials.

scholarly journals Serum CYR61 As A Potential Biomarker for The Diagnosis of Esophagogastric Junction Tumor

2021 ◽  
Author(s):  
Ling-Yu Chu ◽  
Jian-Yuan Zhou ◽  
Yi-Xuan Zhao ◽  
Yan-Ting Ou ◽  
Tian Yang ◽  
...  
Keyword(s):  
Early Stage ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Operating Characteristics ◽  
Tumor Patients ◽  
Chi Square ◽  
Potential Biomarker ◽  
The Difference ◽  
Normal Controls

Background：Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. This study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P&lt;0.0001). The sensitivity, specificity, and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P&gt;0.05). Conclusion: This study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

scholarly journals Neutralization Assessments Reveal High Cardiothoracic Ratio and Old Age as Independent Predictors of Low Neutralizing Antibody Titers in Hemodialysis Patients Receiving a Single Dose of COVID-19 Vaccine

2022 ◽  
Vol 12 (1) ◽  
pp. 68
Author(s):  
Chun-Yu Chen ◽  
Kuan-Ting Liu ◽  
Shin-Ru Shih ◽  
Jung-Jr Ye ◽  
Yih-Ting Chen ◽  
...  
Keyword(s):  
Single Dose ◽  
Old Age ◽  
Neutralizing Antibodies ◽  
Additive Model ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Neutralization Titer ◽  
Cardiothoracic Ratio

Background: Data are lacking regarding predictors of quantification of neutralizing antibodies (nAbs) based on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 50% neutralization titer (NT50) after a single dose of COVID-19 vaccine in hemodialysis (HD) patients. Methods: This prospective single-center study enrolled 200 HD patients and 82 healthy subjects to estimate antibodies against the SARS-CoV-2 viral spike protein 1 and receptor-binding domain after a first dose of a COVID-19 vaccine (ChAdOx1 or mRNA-1273), measured by enzyme-linked immunosorbent assay and applied spline-based generalized additive model regression analysis to predict NT50 converted to international units. Results: After the first dose of ChAdOx1, multiple linear regression showed that age (p = 0.011) and cardiothoracic ratio (p = 0.002) were negatively associated with NT50. Older age (OR = 0.958, p = 0.052) and higher cardiothoracic ratio (OR < 0.001, p = 0.037) could predict negative humoral response (NT50 < 35.13 IU/mL). NT50 was lower in HD patients compared with healthy controls receiving ChAdOx1 (10.68 vs. 43.01 IU/m, p < 0.001) or mRNA-1273 (36.39 vs. 262.2 IU/mL, p < 0.001). ChAdOx1 elicited lower GMTs than mRNA-1273 in the HD cohort (10.68 vs. 36.39 IU/mL, p < 0.001) and in healthy controls (43.01 vs. 262.22 IU/mL, p < 0.001). Conclusion: High cardiothoracic ratio and old age could independently predict a decline in nAb titers in an HD cohort vaccinated with a single dose of ChAdOx1.

scholarly journals Neutralizing Antibody Responses in COVID-19 Convalescent Sera

2020 ◽  
Vol 223 (1) ◽  
pp. 47-55 ◽  
Author(s):  
William T Lee ◽  
Roxanne C Girardin ◽  
Alan P Dupuis ◽  
Karen E Kulas ◽  
Anne F Payne ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
High Titer ◽  
Experimental Treatment ◽  
Neutralizing Antibody ◽  
Maximal Activity ◽  
The United States ◽  
Enzyme Linked Immunosorbent Assay ◽  
United States Food ◽  
Antibody Titers ◽  
Antibody Levels

Abstract Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration’s (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31–35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (&gt;960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.

scholarly journals Evaluation of cerebral glioma using 3T diffusion kurtosis tensor imaging and the relationship between diffusion kurtosis metrics and tumor cellularity

2017 ◽  
Vol 45 (4) ◽  
pp. 1347-1358 ◽  
Author(s):  
Chong Qi ◽  
Song Yang ◽  
Lanxi Meng ◽  
Huiyuan Chen ◽  
Zhenlan Li ◽  
...  
Keyword(s):  
Mean Diffusivity ◽  
Area Under The Curve ◽  
Tumor Grade ◽  
Superior Performance ◽  
Cerebral Glioma ◽  
Operating Characteristics ◽  
Significant Difference ◽  
Characteristics Analysis ◽  
Sensitivity Specificity ◽  
Diffusion Kurtosis

Purpose To evaluate the clinical utility of diffusion kurtosis tensor imaging in the characterization of cerebral glioma and investigate correlations between diffusion and kurtosis metrics with tumor cellularity. Materials and Methods A group of 163 patients (age: 40.5 ± 11.5 years) diagnosed with cerebral glioma underwent diffusion kurtosis tensor imaging with a 3 T scanner. Diffusion and kurtosis metrics were measured in the solid part of tumors, and their abilities to distinguish between tumor grades was evaluated. In addition, we analyzed correlations between the metrics and tumor cellularity. Results Mean kurtosis (MK) revealed a significant difference between each pair of tumor grades ( P < 0.05) and produced the best performance in a receiver operating characteristics analysis (area under the curve [AUC] = 0.89, sensitivity/specificity = 83.3/90). In contrast, mean diffusivity (MD) revealed a significant difference only for tumor grade II versus IV ( P < 0.05). No significant differences between grades were detected with fractional anisotropy (FA; P > 0.05). Thus, kurtosis metrics exhibited a positive and strong correlation with tumor cellularity, while MD exhibited a negative or weak correlation with tumor cellularity. Conclusion Diffusion kurtosis metrics, particularly MK, demonstrated superior performance in distinguishing cerebral glioma of different grades compared with conventional diffusion metrics, and were closely associated with tumor cellularity.

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