Identification of clinical factors related to antibody-mediated immune response to the subfornical organ

Akari Nakamura-Utsunomiya; Satoshi Goda; Seiichi Hayakawa; Sakata Sonoko; Ewout J. Hoorn; Anne Blanchard; Akiko Saito-Hakoda; Haruna Kakimoto; Rumi Hachiya; Miki Kamimura; Rie Kawakita; Shinji Higuchi; Rika Fujimaru; Yoko Shirai; Daichi Miyaoka; Yuki Nagata; Yutaro Kishi; Aya Wada; Akari Mitsuboshi; Kayo Ozaki; Nagisa Komatsu; Hidetaka Niizuma; Junko Kanno; Ikuma Fujiwara; Yukihiro Hasegawa; Tohru Yorifuji; Wendy Brickman; Marie Christine Vantyghem; Kei Yamaguchi; Naoki Goshima; Takeshi Y. Hiyama

doi:10.1111/cen.14737

Identification of clinical factors related to antibody-mediated immune response to the subfornical organ

Akari Nakamura-Utsunomiya^*, Satoshi Goda, Seiichi Hayakawa, Sakata Sonoko, Ewout J. Hoorn, Anne Blanchard, Akiko Saito-Hakoda, Haruna Kakimoto, Rumi Hachiya, Miki Kamimura, Rie Kawakita, Shinji Higuchi, Rika Fujimaru, Yoko Shirai, Daichi Miyaoka, Yuki Nagata, Yutaro Kishi, Aya Wada, Akari Mitsuboshi, Kayo OzakiNagisa Komatsu, Hidetaka Niizuma, Junko Kanno, Ikuma Fujiwara, Yukihiro Hasegawa, Tohru Yorifuji, Wendy Brickman, Marie Christine Vantyghem, Kei Yamaguchi, Naoki Goshima, Takeshi Y. Hiyama

^*Corresponding author for this work

Pediatrics

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

4 Scopus citations

Abstract

Objective: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ. Design: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe. Methods: The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic-pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses. Results: Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p <.05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Na_x channel. Conclusions: The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.

Original language	English (US)
Journal	Clinical Endocrinology
DOIs	https://doi.org/10.1111/cen.14737
State	Accepted/In press - 2022

Keywords

Na channel
ROHHAD syndrome
adipsic hypernatremia
dysnatremia
hypothalamus dysfunction
sensory circumventricular organ
subfornical organ

ASJC Scopus subject areas

Endocrinology
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cen.14737

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Nakamura-Utsunomiya, A., Goda, S., Hayakawa, S., Sonoko, S., Hoorn, E. J., Blanchard, A., Saito-Hakoda, A., Kakimoto, H., Hachiya, R., Kamimura, M., Kawakita, R., Higuchi, S., Fujimaru, R., Shirai, Y., Miyaoka, D., Nagata, Y., Kishi, Y., Wada, A., Mitsuboshi, A., ... Hiyama, T. Y. (Accepted/In press). Identification of clinical factors related to antibody-mediated immune response to the subfornical organ. Clinical Endocrinology. https://doi.org/10.1111/cen.14737

@article{60f1f4fb5568447182dc19ae1d1ae30a,

title = "Identification of clinical factors related to antibody-mediated immune response to the subfornical organ",

abstract = "Objective: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ. Design: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe. Methods: The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic-pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses. Results: Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p <.05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Nax channel. Conclusions: The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.",

keywords = "Na channel, ROHHAD syndrome, adipsic hypernatremia, dysnatremia, hypothalamus dysfunction, sensory circumventricular organ, subfornical organ",

author = "Akari Nakamura-Utsunomiya and Satoshi Goda and Seiichi Hayakawa and Sakata Sonoko and Hoorn, {Ewout J.} and Anne Blanchard and Akiko Saito-Hakoda and Haruna Kakimoto and Rumi Hachiya and Miki Kamimura and Rie Kawakita and Shinji Higuchi and Rika Fujimaru and Yoko Shirai and Daichi Miyaoka and Yuki Nagata and Yutaro Kishi and Aya Wada and Akari Mitsuboshi and Kayo Ozaki and Nagisa Komatsu and Hidetaka Niizuma and Junko Kanno and Ikuma Fujiwara and Yukihiro Hasegawa and Tohru Yorifuji and Wendy Brickman and Vantyghem, {Marie Christine} and Kei Yamaguchi and Naoki Goshima and Hiyama, {Takeshi Y.}",

note = "Funding Information: We thank Drs. J. Caccia, N. Yamaguchi, K. Tamai, N. Ohmori, and H. Kadowaki, for their collaboration in this study. We also thank Prof. M. Noda for procuring participants in this study. This work was supported by MEXT/JSPS KAKENHI (Grant number 21K15894 to ANU), by Forum on Growth Hormone research grant in 2017 (to ANU), and by the Japanese Society for Pediatric Endocrinology (Future Development Grant in 2015 to ANU and 2019 to SS), which was sponsored by Novo Nordisk Pharma Ltd. Publisher Copyright: {\textcopyright} 2022 John Wiley & Sons Ltd.",

year = "2022",

doi = "10.1111/cen.14737",

language = "English (US)",

journal = "Clinical Endocrinology",

issn = "0300-0664",

publisher = "Wiley-Blackwell",

}

Nakamura-Utsunomiya, A, Goda, S, Hayakawa, S, Sonoko, S, Hoorn, EJ, Blanchard, A, Saito-Hakoda, A, Kakimoto, H, Hachiya, R, Kamimura, M, Kawakita, R, Higuchi, S, Fujimaru, R, Shirai, Y, Miyaoka, D, Nagata, Y, Kishi, Y, Wada, A, Mitsuboshi, A, Ozaki, K, Komatsu, N, Niizuma, H, Kanno, J, Fujiwara, I, Hasegawa, Y, Yorifuji, T, Brickman, W, Vantyghem, MC, Yamaguchi, K, Goshima, N & Hiyama, TY 2022, 'Identification of clinical factors related to antibody-mediated immune response to the subfornical organ', Clinical Endocrinology. https://doi.org/10.1111/cen.14737

TY - JOUR

T1 - Identification of clinical factors related to antibody-mediated immune response to the subfornical organ

AU - Nakamura-Utsunomiya, Akari

AU - Goda, Satoshi

AU - Hayakawa, Seiichi

AU - Sonoko, Sakata

AU - Hoorn, Ewout J.

AU - Blanchard, Anne

AU - Saito-Hakoda, Akiko

AU - Kakimoto, Haruna

AU - Hachiya, Rumi

AU - Kamimura, Miki

AU - Kawakita, Rie

AU - Higuchi, Shinji

AU - Fujimaru, Rika

AU - Shirai, Yoko

AU - Miyaoka, Daichi

AU - Nagata, Yuki

AU - Kishi, Yutaro

AU - Wada, Aya

AU - Mitsuboshi, Akari

AU - Ozaki, Kayo

AU - Komatsu, Nagisa

AU - Niizuma, Hidetaka

AU - Kanno, Junko

AU - Fujiwara, Ikuma

AU - Hasegawa, Yukihiro

AU - Yorifuji, Tohru

AU - Brickman, Wendy

AU - Vantyghem, Marie Christine

AU - Yamaguchi, Kei

AU - Goshima, Naoki

AU - Hiyama, Takeshi Y.

N1 - Funding Information: We thank Drs. J. Caccia, N. Yamaguchi, K. Tamai, N. Ohmori, and H. Kadowaki, for their collaboration in this study. We also thank Prof. M. Noda for procuring participants in this study. This work was supported by MEXT/JSPS KAKENHI (Grant number 21K15894 to ANU), by Forum on Growth Hormone research grant in 2017 (to ANU), and by the Japanese Society for Pediatric Endocrinology (Future Development Grant in 2015 to ANU and 2019 to SS), which was sponsored by Novo Nordisk Pharma Ltd. Publisher Copyright: © 2022 John Wiley & Sons Ltd.

PY - 2022

Y1 - 2022

N2 - Objective: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ. Design: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe. Methods: The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic-pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses. Results: Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p <.05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Nax channel. Conclusions: The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.

AB - Objective: We recently reported cases of adipsic hypernatremia caused by autoantibodies against the subfornical organ in patients with hypothalamic-pituitary lesions. This study aimed to clarify the clinical features of newly identified patients with adipsic hypernatremia whose sera displayed immunoreactivity to the mouse subfornical organ. Design: Observational cohort study of patients diagnosed with adipsic hypernatremia in Japan, United States, and Europe. Methods: The study included 22 patients with adipsic hypernatremia but without overt structural changes in the hypothalamic-pituitary region and congenital disease. Antibody response to the mouse subfornical organ was determined using immunohistochemistry. The clinical characteristics were compared between the patients with positive and negative antibody responses. Results: Antibody response to the mouse subfornical organ was detected in the sera of 16 patients (72.7%, female/male ratio, 1:1, 12 pediatric and 4 adult patients). The prolactin levels at the time of diagnosis were significantly higher in patients with positive subfornical organ (SFO) immunoreactivity than in those with negative SFO immunoreactivity (58.9 ± 33.5 vs. 22.9 ± 13.9 ng/ml, p <.05). Hypothalamic disorders were found in 37.5% of the patients with positive SFO immunoreactivity. Moreover, six patients were diagnosed with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation/neural tumor syndrome after the diagnosis of adipsic hypernatremia. Plasma renin activity levels were significantly higher in patients with serum immunoreactivity to the Nax channel. Conclusions: The patients with serum immunoreactivity to the SFO had higher prolactin levels and hypothalamic disorders compared to those without the immunoreactivity. The clinical characteristics of patients with serum immunoreactivity to the subfornical organ included higher prolactin levels and hypothalamic disorders, which were frequently associated with central hypothyroidism and the presence of retroperitoneal tumors.

KW - Na channel

KW - ROHHAD syndrome

KW - adipsic hypernatremia

KW - dysnatremia

KW - hypothalamus dysfunction

KW - sensory circumventricular organ

KW - subfornical organ

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UR - http://www.scopus.com/inward/citedby.url?scp=85128996561&partnerID=8YFLogxK

U2 - 10.1111/cen.14737

DO - 10.1111/cen.14737

M3 - Article

C2 - 35419873

AN - SCOPUS:85128996561

SN - 0300-0664

JO - Clinical Endocrinology

JF - Clinical Endocrinology

ER -

Identification of clinical factors related to antibody-mediated immune response to the subfornical organ

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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