Faculty Opinions recommendation of Potassium channel KIR4.1 as an immune target in multiple sclerosis.

Author(s):  
Marco Rovaris
2020 ◽  
Vol 21 (24) ◽  
pp. 9632
Author(s):  
Michie Imamura ◽  
Osamu Higuchi ◽  
Yasuhiro Maeda ◽  
Akihiro Mukaino ◽  
Mitsuharu Ueda ◽  
...  

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.


2012 ◽  
Vol 367 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Rajneesh Srivastava ◽  
Muhammad Aslam ◽  
Sudhakar Reddy Kalluri ◽  
Lucas Schirmer ◽  
Dorothea Buck ◽  
...  

2014 ◽  
Vol 13 (8) ◽  
pp. 795-806 ◽  
Author(s):  
Adipong Brickshawana ◽  
Shannon R Hinson ◽  
Michael F Romero ◽  
Claudia F Lucchinetti ◽  
Yong Guo ◽  
...  

2014 ◽  
Vol 20 (13) ◽  
pp. 1699-1703 ◽  
Author(s):  
Elodie Nerrant ◽  
Céline Salsac ◽  
Mahmoud Charif ◽  
Xavier Ayrignac ◽  
Clarisse Carra-Dalliere ◽  
...  

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.


US Neurology ◽  
2010 ◽  
Vol 06 (02) ◽  
pp. 76 ◽  
Author(s):  
Aaron Miller ◽  
Amy Perrin Ross ◽  
James Gilbart ◽  
◽  
◽  
...  

Walking impairment is one of the most serious and frequent problems reported by multiple sclerosis (MS) patients. Treatments to restore walking ability are an unmet clinical need. Dalfampridine, a potassium channel blocker, is the first US Food and Drug Administration (FDA)-approved drug to be indicated specifically to improve walking in patients with MS. In clinical trials the drug showed improved walking speeds, demonstrating efficacy in all four types of MS. In phase III trials, dalfampridine provided significant benefits to 35–43% of treated patients. Therefore, it will be critical to manage patient expectations appropriately.


2009 ◽  
Vol 124 (2) ◽  
pp. 95-101 ◽  
Author(s):  
Zoltan Varga ◽  
Tunde Csepany ◽  
Ferenc Papp ◽  
Akos Fabian ◽  
Peter Gogolak ◽  
...  

2014 ◽  
Vol 21 (5) ◽  
pp. 572-579 ◽  
Author(s):  
Livnat Brill ◽  
Lotem Goldberg ◽  
Arnon Karni ◽  
Panayiota Petrou ◽  
Oded Abramsky ◽  
...  

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.


2017 ◽  
Vol 445 ◽  
pp. 53-58 ◽  
Author(s):  
Fabiana Marnetto ◽  
Paola Valentino ◽  
Marzia Caldano ◽  
Antonio Bertolotto

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