scholarly journals A Multiple N-Glucosylated Peptide Epitope Efficiently Detecting Antibodies in Multiple Sclerosis

2020 ◽  
Vol 10 (7) ◽  
pp. 453 ◽  
Author(s):  
Francesca Nuti ◽  
Feliciana Real Fernandez ◽  
Giuseppina Sabatino ◽  
Elisa Peroni ◽  
Barbara Mulinacci ◽  
...  

Diagnostics of Multiple Sclerosis (MS) are essentially based on the gold standard magnetic resonance imaging. Few alternative simple assays are available to follow up disease activity. Considering that the disease can remain elusive for years, identification of antibodies fluctuating in biological fluids as relevant biomarkers of immune response is a challenge. In previous studies, we reported that anti-N-glucosylated (N-Glc) peptide antibodies that can be easily detected in Solid-Phase Enzyme-Linked ImmunoSorbent Assays (SP-ELISA) on MS patients’ sera preferentially recognize hyperglucosylated adhesin of non-typeable Haemophilus Influenzae. Since multivalency can be useful for diagnostic purposes to allow an efficient coating in ELISA, we report herein the development of a collection of Multiple N-glucosylated Peptide Epitopes (N-Glc MEPs) to detect anti-N-Glc antibodies in MS. To this aim, a series of N-Glc peptide antigens to be represented in the N-GlcMEPs were tested in competitive ELISA. We confirmed that the epitope recognized by antibodies shall contain at least 5-mer sequences including the fundamental N-Glc moiety. Using a 4-branched dendrimeric lysine scaffold, we selected the N-Glc MEP 24, carrying the minimal epitope Asn(Glc) anchored to a polyethylene glycol-based spacer (PEG) containing a 19-atoms chain, as an efficient multivalent probe to reveal specific and high affinity anti-N-Glc antibodies in MS.

2017 ◽  
Vol 08 (S 01) ◽  
pp. S136-S138
Author(s):  
Sanjeev Kumar Bhoi ◽  
Suprava Naik ◽  
Jayantee Kalita ◽  
U. K. Misra

ABSTRACTBalo's concentric sclerosis (BCS) is a rare demyelinating lesion considered to be a variant of multiple sclerosis (MS). On magnetic resonance imaging (MRI) Balo's concentric sclerosis shows the typical concentric pattern. We report a case of 10 year old child with BCS who presented as post infectious acute disseminated encephalomyelitis (ADEM). He is asymptomatic and had no relapse after 6 years of follow-up.


2016 ◽  
Vol 23 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Tomas Uher ◽  
Manuela Vaneckova ◽  
Lukas Sobisek ◽  
Michaela Tyblova ◽  
Zdenek Seidl ◽  
...  

Background: Disease progression and treatment efficacy vary among individuals with multiple sclerosis. Reliable predictors of individual disease outcomes are lacking. Objective: To examine the accuracy of the early prediction of 12-year disability outcomes using clinical and magnetic resonance imaging (MRI) parameters. Methods: A total of 177 patients from the original Avonex-Steroids-Azathioprine study were included. Participants underwent 3-month clinical follow-ups. Cox models were used to model the associations between clinical and MRI markers at baseline or after 12 months with sustained disability progression (SDP) over the 12-year observation period. Results: At baseline, T2 lesion number, T1 and T2 lesion volumes, corpus callosum (CC), and thalamic fraction were the best predictors of SDP (hazard ratio (HR) = 1.7–4.6; p ⩽ 0.001–0.012). At 12 months, Expanded Disability Status Scale (EDSS) and its change, number of new or enlarging T2 lesions, and CC volume % change were the best predictors of SDP over the follow-up (HR = 1.7–3.5; p ⩽  0.001–0.017). A composite score was generated from a subset of the best predictors of SDP. Scores of ⩾4 had greater specificity (90%–100%) and were associated with greater cumulative risk of SDP (HR = 3.2–21.6; p < 0.001) compared to the individual predictors. Conclusion: The combination of established MRI and clinical indices with MRI volumetric predictors improves the prediction of SDP over long-term follow-up and may provide valuable information for therapeutic decisions.


2020 ◽  
Vol 6 (1) ◽  
pp. 205521732090248
Author(s):  
Cecilie Jacobsen ◽  
Robert Zivadinov ◽  
Kjell-Morten Myhr ◽  
Turi O Dalaker ◽  
Ingvild Dalen ◽  
...  

Background Multiple sclerosis is often associated with unemployment. The contribution of grey matter atrophy to unemployment is unclear. Objectives To identify magnetic resonance imaging biomarkers of grey matter and clinical symptoms associated with unemployment in multiple sclerosis patients. Methods Demographic, clinical data and 1.5 T magnetic resonance imaging scans were collected in 81 patients at the time of inclusion and after 5 and 10 years. Global and tissue-specific volumes were calculated at each time point. Statistical analysis was performed using a mixed linear model. Results At baseline 31 (38%) of the patients were unemployed, at 5-year follow-up 44 (59%) and at 10-year follow-up 34 (81%) were unemployed. The unemployed patients had significantly lower subcortical deep grey matter volume ( P < 0.001), specifically thalamus, pallidus, putamen and hippocampal volumes, and cortical volume ( P = 0.011); and significantly greater T1 ( P < 0.001)/T2 ( P < 0.001) lesion volume than the employed patient group at baseline. Subcortical deep grey matter volumes, and to a lesser degree cortical volume, were significantly associated with unemployment throughout the follow-up. Conclusion We found significantly greater atrophy of subcortical deep grey matter and cortical volume at baseline and during follow-up in the unemployed patient group. Atrophy of subcortical deep grey matter showed a stronger association to unemployment than atrophy of cortical volume during the follow-up.


1997 ◽  
Vol 3 (3) ◽  
pp. 184-190 ◽  
Author(s):  
P. Kivisäkk ◽  
GV Alm ◽  
WZ Tian ◽  
D. Matusevicius ◽  
S. Fredrikson ◽  
...  

Interferon-β-1b (IFN-β-1b) is an immunomodulatory therapy of multiple sclerosis (MS), reducing the numbers and severity of exacerbations and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-β-1b could be hampered by the development of neutralising antibodies against the compound. Our results confirmed earlier studies, showing that 42% of MS patients treated with IFN-β-1b for more than 3 months had developed neutralising antibodies. The occurrence of binding anti-IFN-β-1b antibodies, presently not believed to impede the clinical efficacy of IFN-β-1b, were demonstrated by an immunoassay in some patients already after I month of treatment and in 78% after 3 months. The development of binding antibodies seemed to be an early phenomenon, preceding the appearance of neutralising antibodies. Antibodies crossreacting with IFN-β-1a and natural IFN-β were also found in a majority of IFN-β-1b treated patients with high titres of binding antibodies. Employing a solid-phase enzyme-linked immunospot (ELISPOT) assay, 68% of MS patients treated with IFN-β-1b for 1 -23 months had elevated numbers of anti-IFN-β-1b-antibody secreting cells in blood, compared to 18% of untreated MS patients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-β-1 b is immunogenic in MS patients. High levels of anti-IFN-β-1b antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseases, suggesting that anti-IFN-β-1b antibodies might also occur spontaneously.


2013 ◽  
Vol 20 (5) ◽  
pp. 566-576 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Rosa Mancinelli ◽  
Laura De Giglio ◽  
Floriana De Angelis ◽  
Valeria Barletta ◽  
...  

Objective: The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated patients with multiple sclerosis (MS) according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment. Methods: A total of 370 patients with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in patients fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity. Results: A total of 192 (51.9%) patients relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either patients fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable patients (all p values <0.001). Conclusion: The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.


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