Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia

Takeshi Y. Hiyama; Shinichi Matsuda; Akihiro Fujikawa; Masahito Matsumoto; Eiji Watanabe; Hiroshi Kajiwara; Fumio Niimura; Masaharu Noda

doi:10.1016/j.neuron.2010.04.017

Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia

Takeshi Y. Hiyama, Shinichi Matsuda, Akihiro Fujikawa, Masahito Matsumoto, Eiji Watanabe, Hiroshi Kajiwara, Fumio Niimura, Masaharu Noda

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

Na_x is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Na_x-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Na_x, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Na_x. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Na_x is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.

Original language	English
Pages (from-to)	508-522
Number of pages	15
Journal	Neuron
Volume	66
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2010.04.017
Publication status	Published - May 1 2010
Externally published	Yes

Keywords

Cellimmuno
Humdisease
Molneuro

ASJC Scopus subject areas

Neuroscience(all)

Access to Document

10.1016/j.neuron.2010.04.017

Cite this

@article{7ef25a5277cd4cc2bf5cd9141d059e21,

title = "Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia",

abstract = "Nax is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Nax, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Nax. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Nax is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.",

keywords = "Cellimmuno, Humdisease, Molneuro",

author = "Hiyama, {Takeshi Y.} and Shinichi Matsuda and Akihiro Fujikawa and Masahito Matsumoto and Eiji Watanabe and Hiroshi Kajiwara and Fumio Niimura and Masaharu Noda",

note = "Funding Information: We are grateful to Dr. Shigeru Ueno (Tokai University School of Medicine at Isehara) for surgical treatment of the patient's tumor, and to Dr. Yasumasa Oh (Tokai University School of Medicine) for supervising the clinical pediatric practice at Tokai University Hospital. We thank Dr. Yasuo Mori (Kyoto University, Japan) for the human TRPV1 expression vectors, Dr. Wolfgang Liedtke (Duke University, NC) for the human TRPV4 expression vector, Dr. Stephen G. Waxman (Yale University, CT) for the HEK293 cell line stably expressing human Na v 1.7, and Dr. David Julius (University of California, San Francisco, CA) for the anti-P2Y 12 antibody. We also thank Ms. Nao Tomita and Yoshiko Isoshima for technical assistance, and Ms. Akiko Kodama for secretarial assistance. This work is supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. ",

year = "2010",

month = may,

day = "1",

doi = "10.1016/j.neuron.2010.04.017",

language = "English",

volume = "66",

pages = "508--522",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia

AU - Hiyama, Takeshi Y.

AU - Matsuda, Shinichi

AU - Fujikawa, Akihiro

AU - Matsumoto, Masahito

AU - Watanabe, Eiji

AU - Kajiwara, Hiroshi

AU - Niimura, Fumio

AU - Noda, Masaharu

N1 - Funding Information: We are grateful to Dr. Shigeru Ueno (Tokai University School of Medicine at Isehara) for surgical treatment of the patient's tumor, and to Dr. Yasumasa Oh (Tokai University School of Medicine) for supervising the clinical pediatric practice at Tokai University Hospital. We thank Dr. Yasuo Mori (Kyoto University, Japan) for the human TRPV1 expression vectors, Dr. Wolfgang Liedtke (Duke University, NC) for the human TRPV4 expression vector, Dr. Stephen G. Waxman (Yale University, CT) for the HEK293 cell line stably expressing human Na v 1.7, and Dr. David Julius (University of California, San Francisco, CA) for the anti-P2Y 12 antibody. We also thank Ms. Nao Tomita and Yoshiko Isoshima for technical assistance, and Ms. Akiko Kodama for secretarial assistance. This work is supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Nax is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Nax, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Nax. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Nax is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.

AB - Nax is the sodium-level sensor of body fluids in the brain involved in sodium homeostasis. Nax-knockout mice do not stop ingesting salt even when dehydrated. Here we report a case with clinical features of essential hypernatremia without demonstrable hypothalamic structural lesions, who was diagnosed as a paraneoplastic neurologic disorder. The patient had autoantibodies directed against Nax, along with a ganglioneuroma composed of Schwann-like cells robustly expressing Nax. The removal of the tumor did not reduce the autoantibody levels or relieve the symptoms. Intravenous injection of the immunoglobulin fraction of the patient's serum into mice induced abnormalities in water/salt intake and diuresis, which led to hypernatremia. In the brains of these mice, cell death was observed along with focal deposits of complement C3 and inflammatory infiltrates in circumventricular organs where Nax is specifically expressed. Our findings thus provide new insights into the pathogenesis of hypernatremia relevant to the sodium-level-sensing mechanism in humans.

KW - Cellimmuno

KW - Humdisease

KW - Molneuro

UR - http://www.scopus.com/inward/record.url?scp=77953263987&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953263987&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2010.04.017

DO - 10.1016/j.neuron.2010.04.017

M3 - Article

C2 - 20510856

AN - SCOPUS:77953263987

SN - 0896-6273

VL - 66

SP - 508

EP - 522

JO - Neuron

JF - Neuron

IS - 4

ER -

Autoimmunity to the sodium-level sensor in the brain causes essential hypernatremia

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this