Low reliability of anti-KIR4.183–120 peptide auto-antibodies in multiple sclerosis patients

2017 ◽  
Vol 24 (7) ◽  
pp. 910-918 ◽  
Author(s):  
Mariapaola Marino ◽  
Giovanni Frisullo ◽  
Gabriele Di Sante ◽  
Daniela Maria Samengo ◽  
Carlo Provenzano ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Amino Acids ◽  
Blood Donors ◽  
Neurological Diseases ◽  
Full Length ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diagnostic Potential ◽  
Reliability Control ◽  
Inward Rectifying Potassium Channel ◽  
Multiple Sclerosis Patients

Background: Multiple sclerosis (MS) is an autoimmune disease for which auto-antibodies fully validated as diagnostic and prognostic biomarkers are widely desired. Recently, an immunoreactivity against the inward rectifying potassium channel 4.1 (KIR4.1) has been reported in a large proportion of a group of MS patients, with amino acids 83–120 being the major epitope. Moreover, a strong correlation between anti-KIR4.183–120 and anti-full-length-protein auto-antibodies titer was reported. However, this finding received limited confirmation. Objective: Validation of the diagnostic potential of anti-KIR4.183–120 antibodies in 78 MS patients, 64 healthy blood donors, and 42 individuals with other neurological diseases. Methods: Analysis of anti-KIR4.183–120 antibodies by enzyme-linked immunosorbent assay (ELISA) using a mouse antiserum we produced as a new ELISA reliability control. Additionally, evaluation of reactivity against 293-T cells transiently transfected with full-length KIR4.1 by flow cytometry. Results: We found antibodies to KIR4.183–120 only in 13 out of 78 (16.6%) MS patients; among these, only 2 were positive for anti-full-length KIR4.1 antibodies. Conclusion: Employing a new reliability control and a new cytofluorometric assay, we cannot support anti-KIR4.183–120 auto-antibodies as a reliable biomarker in MS.

Lack of confirmation of anti-inward rectifying potassium channel 4.1 antibodies as reliable markers of multiple sclerosis

2014 ◽  
Vol 20 (13) ◽  
pp. 1699-1703 ◽  
Author(s):  
Elodie Nerrant ◽  
Céline Salsac ◽  
Mahmoud Charif ◽  
Xavier Ayrignac ◽  
Clarisse Carra-Dalliere ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Potassium Channel ◽  
Immunosorbent Assay ◽  
Neurological Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Lower Prevalence ◽  
Immunofluorescence Analysis ◽  
Specific Staining ◽  
Inward Rectifying Potassium Channel

Background: auto-antibodies against the potassium channel inward rectifying potassium channel 4.1 (Kir4.1) have previously been identified in 46% of patients with multiple sclerosis (MS). Objectives: to confirm these findings. Methods: we evaluated the presence of anti-Kir4.1 antibodies by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence in 268 MS patients, 46 patients with other neurological diseases (OND) and 45 healthy controls. Results: anti-Kir4.1 antibodies were found in 7.5% of MS patients, 4.3% of OND patients and 4.4% of healthy controls. Immunofluorescence analysis did not identify any specific staining. Conclusions: we confirmed the presence of anti-Kir4.1 antibodies in MS patients, but at a much lower prevalence than previously reported.

Practice Effects in Mobile Tests of Cognition, Dexterity & Mobility in Multiple Sclerosis Patients: Data Analysis of a Smartphone–Based Observational Study (Preprint)

2021 ◽  
Author(s):  
Tim Woelfle ◽  
Silvan Pless ◽  
Andrea Wiencierz ◽  
Ludwig Kappos ◽  
Yvonne Naegelin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Diseases ◽  
Clinical Manifestations ◽  
Practice Effect ◽  
Practice Effects ◽  
Linear Phase ◽  
Multiple Sclerosis Patients ◽  
Personalized Health ◽  
Changes Over Time ◽  
Minute Walk

BACKGROUND Smartphones and their inbuilt sensors allow for the collection of a wealth of data about their owners. While passively collected data such as step counts can already provide meaningful insights, active tests allow for measuring function in more specific tasks. This could improve disease characterization and monitoring and could potentially support treatment decisions in multiple sclerosis (MS), a multifaceted chronic neurological disease with highly variable clinical manifestations. One challenge that has to be overcome in the assessment of changes over time is the analysis and interpretation of practice effects. OBJECTIVE In this study, we aimed to identify practice effects in active tests for cognition, dexterity, and mobility in user–scheduled, high–frequency, smartphone–based testing. METHODS We analyzed data from 251 self–declared persons with MS with a minimum of 5 weeks of follow–up and at least 5 tests per domain in the Floodlight Open study, a self–enrolment study accessible by smartphone owners from 16 countries. The collected data are openly available for scientists. Using bounded growth mixed models and quantile regression, we characterized practice effects for three different tests: Symbol Digit Modalities Test (SDMT) for cognition, Finger Pinching for dexterity, and Two Minute Walk for mobility. RESULTS Strong practice effects were found for N=4388 SDMT and N=17945 Finger Pinching tests with modelled boundary improvements of 39.6% (38.6%–40.9%) and 85.9% (83.2%–88.9%) over baseline, respectively. Half of the practice effect was reached after 9 repetitions for SDMT and 27 repetitions for Finger Pinching, 90% were reached after 31 and 89 repetitions, respectively. While baseline performance levels were highly variable across participants, no significant differences between the practice effects in low–performers (5th and 25th percentile), median performers and high performers (75th and 95th percentile) were found for SDMT (β = 1.0–1.2 additional correct responses per repetition in the linear phase). Only small differences were observed for Finger Pinching (β = 0.3–0.7 additional successful pinches per repetition in the linear phase). For N=12997 Two Minute Walk tests, no practice effects were observed at all. CONCLUSIONS Smartphone–based tests promise to help monitor disease trajectories of MS and other chronic neurological diseases. Our findings suggest that strong practice effects in cognitive and dexterity functions have to be accounted for in order to identify disease–related changes in these domains, especially in the context of personalized health and in studies with no comparator arm. In contrast, changes in mobility may be more easily interpreted due to the absence of practice effects.

Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

2010 ◽  
Vol 16 (7) ◽  
pp. 883-887 ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Carmine Tamborino ◽  
Alice Cani ◽  
Elena Negri ◽  
Eleonora Baldi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Disorders ◽  
Epstein Barr Virus ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiple Sclerosis Patients

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

Identification of human herpesviruses 1 to 8 in Tunisian multiple sclerosis patients and healthy blood donors

2011 ◽  
Vol 18 (1) ◽  
pp. 12-19 ◽  
Author(s):  
Nadia Ben Fredj ◽  
Antonella Rotola ◽  
Faten Nefzi ◽  
Saber Chebel ◽  
Roberta Rizzo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blood Donors ◽  
Multiple Sclerosis Patients ◽  
Human Herpesviruses

Silver staining of unconcentrated cerebrospinal fluid in agarose gel (Panagel) electrophoresis.

1984 ◽  
Vol 30 (5) ◽  
pp. 735-736 ◽  
Author(s):  
P D Mehta ◽  
S P Mehta ◽  
B A Patrick
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Silver Staining ◽  
Clinical Laboratory ◽  
Neurological Diseases ◽  
Agarose Gel ◽  
Oligoclonal Igg ◽  
Multiple Sclerosis Patients ◽  
Coomassie Brilliant ◽  
Oligoclonal Igg Bands

Abstract We subjected cerebrospinal fluid (CSF) from 20 patients with multiple sclerosis and 20 patients with other neurological diseases to agarose gel ( Panagel ) electrophoresis followed by staining with silver. Ten microliters of unconcentrated CSF from multiple sclerosis patients containing 0.4 to 0.8 microgram of immunoglobulin G was found to be optimum for detection of oligoclonal IgG bands, so identified by immunofixation. The band patterns for unconcentrated CSF stained with silver were almost identical to those for the same CSF concentrated 40-fold and stained with Coomassie Brilliant Blue. Silver staining thus enables the clinical laboratory to electrophorese unconcentrated CSF on commercially prepared ( Panagel ) plates.

Physical Activity in Prevention of Risk and Disability in Some Neurological Diseases

2014 ◽  
Vol 22 (1) ◽  
pp. 21-27
Author(s):  
Józef Opara
Keyword(s):  
Quality Of Life ◽  
Physical Activity ◽  
Multiple Sclerosis ◽  
Physical Disability ◽  
Neurological Diseases ◽  
Review Of The Literature ◽  
Disability Progression ◽  
Multiple Sclerosis Patients

Abstract The question of the role of physical activity in preventing disability in neurological diseases is the issue which is not in doubt. There is well known that physical activity in Parkinson`s disease and in Multiple Sclerosis patients is less than is the case in the general population. Numerous scientific studies have confirmed the low physical activity of people with PD and MS. Improving physical activity delays the progress of physical disability and has the effect on increasing the quality of life in those two diseases. In this paper an descriptive review of the literature devoted to the effect of physical activity on risk of PD and its impact on disability progression in PD and MS has been presented. The different recommendations for physical activity and different methods of assessment have been described.

scholarly journals The value of csf analysis for the differential diagnosis of HTLV-I associated myelopathy and multiple sclerosis

1995 ◽  
Vol 53 (4) ◽  
pp. 760-765 ◽  
Author(s):  
Marzia Puccioni-Sohler ◽  
Bernd Kitze ◽  
Klaus Felgenhauer ◽  
Iris T. Graef ◽  
Peter Lange ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Neurological Diseases ◽  
Spastic Paraparesis ◽  
Idiopathic Epilepsy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Antibodies ◽  
Varicella Zoster ◽  
Csf Analysis ◽  
Simplex Virus

Cerebrospinal fluid (CSF) and serum of 17 patients with HAM/TSP (HTLV-I associated myelopathy/ tropical spastic paraparesis), six with multiple sclerosis and six with idiopathic epilepsy (non inflammatory control) from Brazil were analysed for the presence of intrathecal synthesis of virus-specific antibodies against measles, rubella, varicella zoster virus and herpes simplex virus by enzyme-linked immunosorbent assay (ELISA). All HAM/TSP and multiple sclerosis cases had an intrathecal immune response (oligoclonal IgG). In HAM/TSP, only 1/17 case showed a polyspecific intrathecal immune response against measles and rubella virus. In multiple sclerosis, specific antibodies against measles and rubella (MRZ response) were observed in all patients but not in the control with idiopathic epilepsy. The diagnostic and theoretical relevance of mono- and polyspecific immune responses is discussed for these chronic neurological diseases.

scholarly journals The Vibration Quantitation Scale (VQS): A Simple, Reproducible Bedside Measure of Sensory Function in Multiple Sclerosis

2004 ◽  
Vol 31 (4) ◽  
pp. 490-493
Author(s):  
J. Carter ◽  
T. Wasser ◽  
S. Statler ◽  
A.D. Rae-Grant
Keyword(s):  
Multiple Sclerosis ◽  
Tuning Fork ◽  
Neurological Diseases ◽  
Statistical Significance ◽  
Sensory Function ◽  
Strongly Correlated ◽  
Sensory Abnormalities ◽  
Multiple Sclerosis Patients ◽  
Disability Severity ◽  
Normal Controls

Objectives:To assess the utility of a bedside measure of sensation (the Vibration Quantitation Scale (VQS)) in patients with multiple sclerosis (MS) and in normal controls. To correlate the VQS with the Kurtzke Expanded Disability Severity Score (EDSS) and sensory abnormalities in these patients.Methods:We developed the VQS and tested its performance in patients with MS of various ages, MS types, and EDSS scores. We compared this with controls (normal volunteers or patients with other neurological diseases) who did not have sensory symptoms. In a subgroup, two examiners measured VQS independently at the same patient visit. Astandard C-128 tuning fork was used for the VQS measurement.Results:The VQS had a good inter-observer reproducibility (r=0.920, p<0.001). The VQS fell with increasing age in normals consistent with declining sensory function. The VQS was significantly lower in the multiple sclerosis patients compared with age - matched controls (p<0.001). Abnormalities in VQS were present in patients with brief duration of MS (<5 years) and low EDSS scores, correlating with the presence of sensory abnormalities early in the disease course in some patients. There was a strong correlation between the VQS and EDSS (r=-0.509). The VQS correlated with abnormal sensation in the hands (r=0.310), but did not meet statistical significance for abnormal sensation in the feet or face. Asecond cohort of MS patients was studied using a modified VQS measure (single stimulation, omitting forehead measurement). This reconfirmed the correlation between the modified VQS and EDSS as well as with age. The modified VQS may be useful in clinical practice since it takes little time and is strongly correlated with the EDSS (r=0.578).Conclusion:The VQS provides a continuous sensory scale applicable in most patients with MS, which is measurable with standard bedside equipment, and which may avoid some of the pitfalls of sensory scoring in MS.

T cells from multiple sclerosis patients recognize immunoglobulin G from cerebrospinal fluid

2003 ◽  
Vol 9 (3) ◽  
pp. 228-234 ◽  
Author(s):  
T Holmøy ◽  
B Vandvik ◽  
F Vartdal
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
T Cell ◽  
Mononuclear Cells ◽  
Neurological Diseases ◽  
Affinity Maturation ◽  
Peripheral Blood Mononuclear ◽  
Number Of Patients ◽  
Multiple Sclerosis Patients

Idiotopic sequences are created after V, D and J recombinations and by somatic mutations during affinity maturation of immuglobulin (Ig) molecules, and may therefore be potential immunogenic epitopes. Idiotope-specific T cells are able to activate and sustain the B cells producing such idiotopes. It is therefore possible that idiotope-specific intrathecal T cells could help maintain the persisting intrathecal synthesis of oligoclonal IgG observed in patients with multiple sclerosis (MS). This study was undertaken to examine T-cell responses to cerebrospinal fluid (CSF) IgG. Peripheral blood mononuclear cells (PBMC) from 14 of 21 MS patients and four of 17 control patients with other neurological diseases proliferated upon stimulation with autologous C SF IgG, while five and three, respectively, responded to serum IgG. By comparison, responses to myelin basic protein were recorded in only four MS and three control patients. Data from a limited number of patients indicate that the C SF IgG responsive cells were CD4+ and human leucocyte antigen DR restricted, that PBMC also respond to C SF IgG from other MS patients and that the C SF may contain T cells responding to autologous C SF IgG. This suggests that C SF IgG, or substances bound to this IgG, may represent T-cell immunogens, which could contribute to the intrathecal immune response in MS.

An MRI study of Chlamydia pneumoniae infection in Italian multiple sclerosis patients

2003 ◽  
Vol 9 (5) ◽  
pp. 467-471 ◽  
Author(s):  
L ME Grimaldi ◽  
A Pincherle ◽  
F Martinelli-Boneschi ◽  
M Filippi ◽  
F Patti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chlamydia Pneumoniae ◽  
Neurological Diseases ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Mri Study

We amplified sequences of the Chlamydia pneumoniae (C P) major-outer membrane protein in the cerebrospinal fluid (CSF) from 23 of 107 (21.5%) relapsing-remitting or secondary progressive multiple sclerosis (MS) patients and two of 77 (2.6%) patients with other neurological diseases (OND) (P =0.00022). C P+ patients showed magnetic resonance imaging (MRI) evidence of more active disease (P =0.02) compared to CP-MS patients and tended to have an anticipation of age at disease onset (32.39-12 versus 28.59-10 years; P =ns) causing a longer disease duration (7.59-5 versus 4.49-4 years; P =0.016) at the time of clinical evaluation. These findings, although indirectly, suggest that C P infection of the central nervous system (C NS) might affect disease course in a subgroup of MS patients.

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