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.

Increased anti-KIR4.1 antibodies in multiple sclerosis: Could it be a marker of disease relapse?

2014 ◽  
Vol 21 (5) ◽  
pp. 572-579 ◽  
Author(s):  
Livnat Brill ◽  
Lotem Goldberg ◽  
Arnon Karni ◽  
Panayiota Petrou ◽  
Oded Abramsky ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Potassium Channel ◽  
Functional Properties ◽  
Clinical Characteristics ◽  
Serum Levels ◽  
Demyelinating Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Disease Relapse ◽  
Disease Exacerbation

Background: Screening of putative autoimmune targets in multiple sclerosis (MS) revealed a proportion of patients carrying antibodies (Abs) against KIR4.1, a potassium channel that shares functional properties with AQP4. Both are localized at the perivascular astrocytic processes. Aims: To measure anti-KIR4.1 Abs in the serum of MS and neuromyelitis optica (NMO) patients, and to identify the clinical and laboratory characteristics of patients harboring anti-KIR4.1 Abs. Methods: We measured anti-KIR4.1 Abs in serum, using the peptide KIR4.1 (83–120) enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of anti-KIR4.1 Abs were significantly higher in MS and NMO patients than in healthy controls (HCs); with Abs detected in 21 of 80, 10 of 45, and 2 of 32 individuals, respectively (MS versus HC, p < 0.05). The level of anti-KIR4.1 Abs was significantly higher during MS relapse, versus remission ( p = 0.04). The clinical characteristics of our study patients did not vary based on KIR4.1 positivity. Conclusions: Anti-KIR4.1 Abs were found in similar proportions of patients with MS and NMO, at a significantly higher level than observed in HCs; consequently, the presence of Abs does not discriminate between these demyelinating diseases. However, anti-KIR4.1 Ab levels differed in MS patients during relapse and remission; as such, they may represent a marker of disease exacerbation.

Antibodies to the axolemma-enriched fraction in the cerebrospinal fluid and serum of patients with multiple sclerosis and other neurological diseases

1997 ◽  
Vol 3 (6) ◽  
pp. 363-369 ◽  
Author(s):  
JA Rawes ◽  
VP Calabrese ◽  
OA Khan ◽  
GH DeVries
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Immunosorbent Assay ◽  
Neurological Diseases ◽  
Enzyme Linked Immunosorbent Assay ◽  
Elisa Technique

Antibodies to an axolemma-enriched fraction (AEF) antigen have been detected in the cerebrospinal fluid (CSF) and serum of patients with Multiple Sclerosis (MS) using an enzyme-linked immunosorbent assay (ELISA). A marginal elevation (P < 0.08) of anti-AEF lgG was found in MS CSF when compared with OND samples. When CSF was diluted to a standardized lgG concentration, the anti-AEF lgG level in MS CSF was significantly elevated (P=0.007) when compared to OND CSF. MS serum was also found to contain a significantly higher level (P < 0.00 I ) of anti-AEF lgG when compared to OND serum using the ELISA technique.

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.

Chitinase 3-like 1 is not a target antigen in patients with multiple sclerosis

2020 ◽  
pp. 135245852098014
Author(s):  
Manuel Comabella ◽  
Claudia Deutschmann ◽  
Luciana Midaglia ◽  
Peter Schierack ◽  
Júlia Martínez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immunosorbent Assay ◽  
Prognostic Biomarker ◽  
Enzyme Linked Immunosorbent Assay ◽  
Target Antigen ◽  
Healthy Controls ◽  
Secondary Progressive ◽  
Inflammatory Conditions ◽  
Relapsing Remitting ◽  
Ms Pathogenesis

Autoimmunity to chitinase 3-like 1 (CHI3L1) has recently been reported in hepatic and bowel inflammatory conditions. Considering that CHI3L1 plays a role as prognostic biomarker in multiple sclerosis (MS), here we investigated CHI3L1 as potential autoantigenic target in the disease. We determined serum CHI3L1 autoantibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 60 untreated MS patients with different clinical forms of the disease and 20 healthy controls (HC). IgG levels to CHI3L1 were similar between patients with relapsing-remitting MS, primary and secondary progressive MS, and HC. These findings do not support a role for CHI3L1 autoantibodies in MS pathogenesis.

Quantitative measurement of anti-aquaporin-4 antibodies by enzyme-linked immunosorbent assay using purified recombinant human aquaporin-4

2011 ◽  
Vol 18 (5) ◽  
pp. 578-586 ◽  
Author(s):  
Woojun Kim ◽  
Ji-Eun Lee ◽  
Xue Feng Li ◽  
Su-Hyun Kim ◽  
Byeong-Gu Han ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Activity ◽  
Immunosorbent Assay ◽  
Neurological Diseases ◽  
Aquaporin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Marker ◽  
Longitudinal Measurement ◽  
Longitudinal Measurements ◽  
Baculovirus System

Background: Antibodies to aquaporin-4 (AQP4-Ab), known as NMO-IgG, are a sensitive and specific marker for neuromyelitis optica (NMO). Methods: To develop an enzyme-linked immunosorbent assay (ELISA) for AQP4-Ab, we expressed M23 isoform of human AQP4 in a baculovirus system, and used it as an antigen. We measured AQP4-Ab in the sera of 300 individuals: 64 with definite NMO, 31 with high-risk NMO, 105 with multiple sclerosis (MS), 57 with other neurological diseases (ONDs), and 43 healthy controls. We also performed longitudinal measurements of AQP4–Ab in 787 samples collected from 51 patients with definite or high-risk NMO. Results: AQP4-Abs were positive in 72% with definite NMO, 55% with high-risk NMO, and 4% with MS, but none of the OND patients and the healthy individuals. The longitudinal measurement showed AQP4-Ab levels correlating with disease activity. Out of 38 initially seropositive patients, 21 became seronegative under effective immunosuppressive therapy. During most relapses, the serum AQP4-Ab levels were either high or rising compared with the previous value, although rising AQP4-Ab levels did not always lead to acute exacerbation. Two of the 13 initially seronegative patients converted to seropositive following acute exacerbations. Conclusions: We established an AQP4-Ab ELISA, which could be a potential monitoring tool of disease activity.

scholarly journals Serological profile of John Cunningham virus (JCV) in patients with multiple sclerosis

2018 ◽  
Vol 76 (9) ◽  
pp. 588-591 ◽  
Author(s):  
Luciana Prats Branco ◽  
Tarso Adoni ◽  
Samira Luisa Apostolos-Pereira ◽  
Joseph Bruno Bidin Brooks ◽  
Eber Castro Correa ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Events ◽  
Progressive Multifocal Leukoencephalopathy ◽  
Immunosorbent Assay ◽  
Treatment Options ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Antibodies ◽  
John Cunningham Virus ◽  
Blood Tests ◽  
Serological Profile

ABSTRACT Treatment options for multiple sclerosis (MS) have changed over the last few years, bringing about a new category of drugs with more efficient profiles. However, these drugs have come with a whole new profile of potential adverse events that neurologists have to learn well and quickly. One of the most feared complications of these MS treatments is progressive multifocal leukoencephalopathy caused by the reactivation of the John Cunningham virus (JCV). Objective: To identify the serologic profile of JCV in patients with MS. Methods: Data on serum antibodies for JCV were obtained using the enzyme-linked immunosorbent assay provided by the STRATIFY-JCV program. Results: A total of 1,501 blood tests were obtained from 1,102 patients with MS. There were 633 patients (57.1%) who were positive for antibodies for JCV and 469 patients who were negative (42.9%). Twenty-three patients became positive after initially having negative JCV antibody status. The rate of seroconversion was 18.5% over 22 months. Conclusion: The JCV serologic profile and seroconversion in Brazilian patients were similar to those described in other countries.

scholarly journals Inflammation-related plasma and CSF biomarkers for multiple sclerosis

2020 ◽  
Vol 117 (23) ◽  
pp. 12952-12960 ◽  
Author(s):  
Jesse Huang ◽  
Mohsen Khademi ◽  
Lars Fugger ◽  
Örjan Lindhe ◽  
Lenka Novakova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
Area Under The Curve ◽  
Csf Biomarkers ◽  
Healthy Controls ◽  
Protein Biomarkers ◽  
Neurofilament Light Chain ◽  
Diagnostic Efficacy ◽  
Neurofilament Light

Effective biomarkers for multiple sclerosis diagnosis, assessment of prognosis, and treatment responses, in particular those measurable in blood, are largely lacking. We have investigated a broad set of protein biomarkers in cerebrospinal fluid (CSF) and plasma using a highly sensitive proteomic immunoassay. Cases from two independent cohorts were compared with healthy controls and patients with other neurological diseases. We identified and replicated 10 cerebrospinal fluid proteins including IL-12B, CD5, MIP-1a, and CXCL9 which had a combined diagnostic efficacy similar to immunoglobulin G (IgG) index and neurofilament light chain (area under the curve [AUC] = 0.95). Two plasma proteins, OSM and HGF, were also associated with multiple sclerosis in comparison to healthy controls. Sensitivity and specificity of combined CSF and plasma markers for multiple sclerosis were 85.7% and 73.5%, respectively. In the discovery cohort, eotaxin-1 (CCL11) was associated with disease duration particularly in patients who had secondary progressive disease (PCSF< 4 × 10−5,Pplasma< 4 × 10−5), and plasma CCL20 was associated with disease severity (P= 4 × 10−5), although both require further validation. Treatment with natalizumab and fingolimod showed different compartmental changes in protein levels of CSF and peripheral blood, respectively, including many disease-associated markers (e.g., IL12B, CD5) showing potential application for both diagnosing disease and monitoring treatment efficacy. We report a number of multiple sclerosis biomarkers in CSF and plasma for early disease detection and potential indicators for disease activity. Of particular importance is the set of markers discovered in blood, where validated biomarkers are lacking.

scholarly journals Anti-Kir4.1 Antibodies in Multiple Sclerosis: Specificity and Pathogenicity

2020 ◽  
Vol 21 (24) ◽  
pp. 9632
Author(s):  
Michie Imamura ◽  
Osamu Higuchi ◽  
Yasuhiro Maeda ◽  
Akihiro Mukaino ◽  
Mitsuharu Ueda ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Neurological Diseases ◽  
Initial Study ◽  
Research Groups ◽  
Antibody Testing ◽  
Follow Up Studies ◽  
Immune Target

The glial cells in the central nervous system express diverse inward rectifying potassium channels (Kir). They express multiple Kir channel subtypes that are likely to have distinct functional roles related to their differences in conductance, and sensitivity to intracellular and extracellular factors. Dysfunction in a major astrocyte potassium channel, Kir4.1, appears as an early pathological event underlying neuronal phenotypes in several neurological diseases. The autoimmune effects on the potassium channel have not yet been fully described in the literature. However, several research groups have reported that the potassium channels are an immune target in patients with various neurological disorders. In 2012, Srivastava et al. reported about Kir4.1, a new immune target for autoantibodies in patients with multiple sclerosis (MS). Follow-up studies have been conducted by several research groups, but no clear conclusion has been reached. Most follow-up studies, including ours, have reported that the prevalence of Kir4.1-seropositive patients with MS was lower than that in the initial study. Therefore, we extensively review studies on the method of antibody testing, seroprevalence of MS, and other neurological diseases in patients with MS. Finally, based on the role of Kir4.1 in MS, we consider whether it could be an immune target in this disease.

scholarly journals Altered Maternal Serum Matrix Metalloproteinases MMP-2, MMP-3, MMP-9, and MMP-13 in Severe Early- and Late-Onset Preeclampsia

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Marzena Laskowska
Keyword(s):  
Matrix Metalloproteinases ◽  
Pregnant Women ◽  
Immunosorbent Assay ◽  
Early Onset ◽  
Late Onset ◽  
Maternal Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Control Subjects ◽  
Early Onset Preeclampsia

Objective. The aim of this study was to determine whether maternal serum matrix metalloproteinases 2, 3, 9, and 13 levels differ in early- and late-onset preeclampsia and uncomplicated pregnancies. Patients and Methods. The study was carried out in 125 pregnant women (29 with early-onset preeclampsia; 31 preeclamptic patients with late-onset preeclampsia; and 65 healthy pregnant controls). Levels of MMP-2, MMP-3, MMP-9, and MMP-13 were measured in the maternal serum using an enzyme-linked immunosorbent assay. Results. Maternal serum MMP-2 levels in both the groups of preeclamptic women were significantly higher than those in the controls. Levels of MMP-3 were significantly higher in preeclamptic patients with early-onset disease; however, the MMP-3 levels in patients with late-onset preeclampsia were similar to those observed in the control subjects. MMP-9 levels were lower whereas the levels of MMP-13 were higher in both preeclamptic groups of pregnant women than in the healthy controls, but these differences were statistically insignificant. Conclusions. One important finding of the present study was that MMP-3 appears to be involved solely in early-onset preeclampsia, but not in late-onset preeclampsia. Higher levels of MMP-2 and MMP-13 and lower levels of MMP-9 seem to be related to both early- and late-onset severe preeclampsia.

scholarly journals Diagnosis of Visceral Leishmaniasis by Enzyme-Linked Immunosorbent Assay Using Urine Samples

2002 ◽  
Vol 9 (4) ◽  
pp. 789-794 ◽  
Author(s):  
Mohammad Zahidul Islam ◽  
Makoto Itoh ◽  
S. M. Shamsuzzaman ◽  
Rusella Mirza ◽  
Farzana Matin ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Sensitivity And Specificity ◽  
Immunosorbent Assay ◽  
Leishmania Donovani ◽  
Laboratory Diagnosis ◽  
Urine Samples ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Serum Samples ◽  
Crude Antigen

ABSTRACT A diagnostic method has been developed to detect anti-Leishmania donovani immunoglobulin G (IgG) in urine by enzyme-linked immunosorbent assay (ELISA). In measuring anti-L. donovani IgG, IgA, and IgM in urine, the method performed best in the detection of IgG. The sensitivity and specificity of the assay were determined with panels of urine samples from 62 visceral leishmaniasis (VL) patients, 59 healthy controls from areas of endemicity, 53 healthy controls from areas of nonendemicity, 59 malaria patients, 13 tuberculosis patients, 23 cutaneous leishmaniasis patients, and 7 patients with other diseases. Using L. donovani promastigote crude antigen, the test had 93.5% sensitivity (58 positives of 62 VL patient samples) and 89.3% specificity (191 negatives of 214 non-VL patient samples). The ELISA with acetone-treated L. donovani promastigote antigen raised the sensitivity and specificity to 95.0 and 95.3%, respectively. Western blot analysis revealed that most of the samples that cross-reacted with crude antigen in ELISA did not recognize any antigenic component of L. donovani crude antigen. We also checked 40 serum samples from the same group of VL patients for anti-L. donovani IgG and got 90.0% sensitivity with both crude and acetone-treated antigens. As collection of urine is much easier than collection of serum, the detection of anti-L. donovani IgG in urine with acetone-treated antigen will be useful in epidemiological studies. It could be an adjunct of laboratory diagnosis.

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