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February 11, 2014; 82 (6) Article

Potassium channel KIR4.1-specific antibodies in children with acquired demyelinating CNS disease

Verena Kraus, Rajneesh Srivastava, Sudhakar Reddy Kalluri, Ulrich Seidel, Markus Schuelke, Mareike Schimmel, Kevin Rostasy, Steffen Leiz, Stuart Hosie, Verena Grummel, Bernhard Hemmer
First published January 10, 2014, DOI: https://doi.org/10.1212/WNL.0000000000000097
Verena Kraus
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Rajneesh Srivastava
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Sudhakar Reddy Kalluri
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Ulrich Seidel
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Markus Schuelke
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Mareike Schimmel
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Kevin Rostasy
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Steffen Leiz
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Stuart Hosie
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Verena Grummel
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Bernhard Hemmer
From the Departments of Pediatrics (V.K.) and Neurology (R.S., S.R.K., V.G., B.H.), Klinikum rechts der Isar, Technische Universität, Munich; Department of Neuropediatrics (U.S., M.S.), Charité Universitätsmedizin, Berlin; Department of Pediatrics (M.S.), Hospital Augsburg, Germany; Department of Neuropediatrics (K.R.), University Hospital Innsbruck, Austria; Department of Pediatrics (S.L.), Hospital Dritter Orden, Munich; Department of Pediatric Surgery (S.H.), Städtisches Klinikum München GmbH, Klinikum Schwabing, Munich; and Munich Cluster for Systems Neurology (SyNergy) (B.H.), Munich, Germany.
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Citation
Potassium channel KIR4.1-specific antibodies in children with acquired demyelinating CNS disease
Verena Kraus, Rajneesh Srivastava, Sudhakar Reddy Kalluri, Ulrich Seidel, Markus Schuelke, Mareike Schimmel, Kevin Rostasy, Steffen Leiz, Stuart Hosie, Verena Grummel, Bernhard Hemmer
Neurology Feb 2014, 82 (6) 470-473; DOI: 10.1212/WNL.0000000000000097

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Abstract

Objective: A serum antibody against the inward rectifying potassium channel KIR4.1 (KIR4.1-IgG) was recently discovered, which is found in almost half of adult patients with multiple sclerosis. We investigated the prevalence of KIR4.1-IgG in children with acquired demyelinating disease (ADD) of the CNS. We also compared antibody responses to KIR4.1 and myelin oligodendrocyte glycoproteins (MOGs), another potential autoantigen in childhood ADDs.

Methods: We measured KIR4.1-IgG by ELISA in children with ADD (n = 47), other neurologic disease (n = 22), and autoimmune disease (n = 22), and in healthy controls (HCs) (n = 18). One hundred six samples were also measured by capture ELISA. Binding of KIR4.1-IgG human subcortical white matter was analyzed by immunofluorescence. Anti-MOG antibodies were measured using a cell-based assay.

Results: KIR4.1-IgG titers were significantly higher in children with ADD compared with all control groups by ELISA and capture ELISA (p < 0.0001, p < 0.0001). Overall, 27 of 47 patients with ADD (57.45%) but none of the 62 with other neurologic disease or autoimmune disease or the HCs (0%) were KIR4.1-IgG antibody positive by ELISA. Sera containing KIR4.1-IgG stained glial cells in brain tissue sections. No correlation among KIR4.1-IgG, age, or MOG-IgG was observed in the ADD group.

Conclusion: Serum antibodies to KIR4.1 are found in the majority of children with ADD but not in children with other diseases or in HCs. These findings suggest that KIR4.1 is an important target of autoantibodies in childhood ADD.

GLOSSARY

ADD=
acquired demyelinating disease;
ADEM=
acute disseminated encephalomyelitis;
CIS=
clinically isolated syndrome;
DEM=
demyelinating encephalomyelitis;
HC=
healthy control;
IgG=
immunoglobulin G;
MDEM=
multiphasic demyelinating encephalomyelitis;
MOG=
myelin oligodendrocyte glycoprotein;
MS=
multiple sclerosis;
OD=
optical density;
OND=
other neurologic disease

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received August 21, 2012.
  • Accepted in final form August 15, 2013.
  • © 2014 American Academy of Neurology
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