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.

Rituximab in patients with pediatric multiple sclerosis and other demyelinating disorders of the CNS: Practical considerations

2020 ◽  
pp. 135245852093279 ◽  
Author(s):  
Angelo Ghezzi ◽  
Brenda Banwell ◽  
Amit Bar-Or ◽  
Tanuja Chitnis ◽  
Russell C Dale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pediatric Patients ◽  
Neurological Diseases ◽  
Duration Of Treatment ◽  
Pediatric Multiple Sclerosis ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
Anti Cd20 ◽  
Demyelinating Disorders

Anti-CD20 therapies have established efficacy in the treatment of immune-mediated neurological and non-neurological diseases. Rituximab, one of the first B-cell-directed therapies, is relatively inexpensive compared to newer anti-CD20 molecules, is available in many countries, and has been used off-label in pediatric patients with neuroimmune conditions. The objective of this paper is to describe the experience with rituximab in pediatric multiple sclerosis and other inflammatory immune-mediated disorders of the central nervous system (CNS), and to define a protocol for its use in clinical practice, in particular addressing doses, interval of administration, duration of treatment, and tests to perform at baseline and during follow-up.

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.

scholarly journals Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA

2009 ◽  
Vol 15 (1) ◽  
pp. 28-35 ◽  
Author(s):  
E Iacobaeus ◽  
C Ryschkewitsch ◽  
M Gravell ◽  
M Khademi ◽  
E Wallstrom ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Copy Number ◽  
Jc Virus ◽  
Neurological Diseases ◽  
Csf Cells ◽  
Increased Risk ◽  
Low Copy Number ◽  
Patient At Risk

Objective 1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML). Methods The prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a single sample, and peripheral blood cells in a subgroup of MS ( n = 49), CIS ( n = 14) and OND ( n = 53). Results A low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus. Conclusion A low copy number of JCV DNA may occasionally be observed both in MS and other diseases and may occur as part of the normal biology of JC virus in humans. This study does not support the hypothesis that patients with MS would be at increased risk to develop PML, and consequently screening of CSF as a measurable risk for PML is not useful.

Hexosylceramides as intrathecal markers of worsening disability in multiple sclerosis

2014 ◽  
Vol 21 (10) ◽  
pp. 1271-1279 ◽  
Author(s):  
Antonio Checa ◽  
Mohsen Khademi ◽  
Daniel G Sar ◽  
Jesper Z Haeggström ◽  
Jon O Lundberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Neurological Diseases ◽  
Control Groups ◽  
Promising Candidate ◽  
Fatty Acid Chain ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Liquid Chromatography Tandem Mass

Background: Sphingolipids are important components of neurons and the myelin sheath whose levels are altered in multiple sclerosis (MS). Objectives: We aimed to determine if cerebrospinal fluid (CSF) sphingolipids can be used as markers of MS disease progression. Methods: Using liquid chromatography tandem mass spectrometry, we analysed sphingolipids in CSF from 134 individuals. The MS group included 65 patients divided into 41 relapsing–remitting MS (RRMS) and 24 progressive MS (ProgMS). In addition, a group of 13 early MS/clinically isolated syndrome (EarlyMS) and two control groups consisting of 38 individuals with other neurological diseases (OND) and 18 OND with signs of inflammation (iOND) were analysed. A follow-up study included 17 additional RRMS patients sampled at two time points 4.7±1.7 years apart. Results: Levels of sphingomyelin (SM)- and hexosylceramide (HexCer)-derived sphingolipids increased in the CSF of patients with MS independently of the fatty acid chain length in RRMS ( p<0.05). Levels of palmitic acid (16:0)-containing HexCer (HexCer16:0) increased significantly in ProgMS compared with the OND ( p<0.001), iOND ( p<0.05) and EarlyMS ( p<0.01) groups and correlated with Expanded Disability Status Scale in RRMS in both studies ( p=0.048; p=0.027). Conclusion: HexCer16:0 is a promising candidate marker of disease progression in MS, especially in RRMS.

scholarly journals Potassium Channel KIR4.1 as an Immune Target in Multiple Sclerosis

2012 ◽  
Vol 367 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Rajneesh Srivastava ◽  
Muhammad Aslam ◽  
Sudhakar Reddy Kalluri ◽  
Lucas Schirmer ◽  
Dorothea Buck ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Potassium Channel ◽  
Immune Target

GLATIRAMER ACETATE AND PREGNANCY IN WOMEN WITH MULTIPLE SCLEROSIS – RESULTS FROM THE GERMAN MULTIPLE SCLEROSIS AND PREGNANCY REGISTRY

2015 ◽  
Vol 101 (1) ◽  
pp. e1.35-e1 ◽  
Author(s):  
Sandra Herbstritt ◽  
Ralf Gold ◽  
Kerstin Hellwig
Keyword(s):  
Multiple Sclerosis ◽  
Glatiramer Acetate ◽  
Perinatal Outcome ◽  
Neurological Diseases ◽  
Reproductive Age ◽  
Limited Data ◽  
The Central Nervous System ◽  
Exposure During Pregnancy ◽  
Pregnancy Registry

ObjectiveTo determine the effect of glatiramer acetate (GLAT) exposure during pregnancy on perinatal outcome in women with multiple sclerosis (MS).BackgroundMS is one of the most common neurological diseases of the central nervous system, which mainly affects young women of reproductive age.Only limited data are available on whether GLAT exposure during pregnancy has an effect on perinatal outcome.MethodsWe compared the outcome of pregnancies of patients with MS exposed to GLAT with pregnancies of unexposed controls. Women with MS were enrolled into the German Multiple Sklerosis and pregnancy registry. Data were assessed with a standardized questionnaire during pregnancy and the postpartum year. Detailed information on course of MS, concomitant medication, pregnancy course and outcome was obtained.ResultsWe collected data on 230 pregnancies: 135 with exposure to GLAT and 95 MS controls unexposed to disease-modifying therapies (DMTs) during pregnancy.While 25 of the exposed pregnancies are still ongoing we did not document any malformation in the first 110 GLAT exposed pregnancies with at least 6 months postpartum follow up. The rate of spontaneous abortions did not differ compared to unexposed controls. 3 (3.15%) infants of the DMT unexposed women were born with malformations of non-genetic origin and 1 (0.95%) newborn was diagnosed with Wolf Hirschhorn syndrome.ConclusionsGLAT exposure does not constitute a major human teratogen or influence outcome of pregnancy negatively compared to untreated women with MS. Final data including the outcome of ongoing pregnancies will be presented at the time of the meeting.

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