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Anti-ganglionic AChR antibodies in Japanese patients with motility disorders

  • Original Article—Alimentary Tract
  • Published:
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Abstract

Background

The existence of several autoantibodies suggests an autoimmune basis for gastrointestinal (GI) dysmotility. Whether GI motility disorders are features of autoimmune autonomic ganglionopathy (AAG) or are related to circulating anti-ganglionic acetylcholine receptor (gAChR) antibodies (Abs) is not known. The aim of this study was to determine the associations between autonomic dysfunction, anti-gAChR Abs, and clinical features in patients with GI motility disorders including achalasia and chronic intestinal pseudo-obstruction (CIPO).

Methods

First study: retrospective cohort study and laboratory investigation. Samples from 123 patients with seropositive AAG were obtained between 2012 and 2017. Second study: prospective study. Samples from 28 patients with achalasia and 14 patients with CIPO were obtained between 2014 and 2016, and 2013 and 2017, respectively. In the first study, we analyzed clinical profiles of seropositive AAG patients. In the second study, we compared clinical profiles, autonomic symptoms, and results of antibody screening between seropositive, seronegative achalasia, and CIPO groups.

Results

In the first study, we identified 10 patients (8.1%) who presented with achalasia, or gastroparesis, or paralytic ileus. In the second study, we detected anti-gAChR Abs in 21.4% of the achalasia patients, and in 50.0% of the CIPO patients. Although patients with achalasia and CIPO demonstrated widespread autonomic dysfunction, bladder dysfunction was observed in the seropositive patients with CIPO as a prominent clinical characteristic of dysautonomia.

Conclusions

These results demonstrate a significant prevalence of anti-gAChR antibodies in patients with achalasia and CIPO. Anti-gAChR Abs might mediate autonomic dysfunction, contributing to autoimmune mechanisms underlying these GI motility disorders.

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Abbreviations

AAG:

Autoimmune autonomic ganglionopathy

Abs:

Antibodies

AGID:

Autoimmune gastrointestinal dysmotility

AI:

Antibody index

CIPO:

Chronic intestinal pseudo-obstruction

COMPASS 31:

Composite autonomic symptom score 31

DES:

Diffuse esophageal spasms

gAChR:

Ganglionic acetylcholine receptor

GAD:

Glutamic acid decarboxylase

GI dysmotility:

Gastrointestinal dysmotility

HC:

Healthy controls

H/M:

Heart to mediastinum

IVMP:

Intravenous methylprednisolone

IVIg:

Intravenous immunoglobulin

LIPS:

Luciferase immunoprecipitation system

OH:

Orthostatic hypotension

OI:

Orthostatic intolerance

PLEX:

Plasma exchange

PSL:

Prednisolone

RLU:

Relative luminescence units

VGCC:

Voltage-gated calcium channel

VGKC:

Voltage-gated potassium channel

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Acknowledgements

This study was supported by the Neuroimmunological Disease Research Committee and the Ministry of Health, Labor, and Welfare, Japan, and the Ministry of Education, Culture, Sports, Science, and Technology of Japan (JSPS KAKENHI Grant Number 25461305).

Author information

Author notes

  1. Akihiro Mukaino and Hitomi Minami contributed equally to this work.

Authors and Affiliations

  1. First Department of Internal Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Akihiro Mukaino

  2. Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Hitomi Minami, Hajime Isomoto & Kazuhiko Nakao

  3. Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Hitomi Hamamoto, Fumisato Sasaki & Akio Ido

  4. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Eikichi Ihara & Yoshihiro Ogawa

  5. Department of Neuroimmunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

    Yasuhiro Maeda & Shunya Nakane

  6. Department of Clinical Research, Nagasaki Kawatana Medical Center, 2005-1 Shimogumigo, Kawatanacho, Higashisonogigun, Nagasaki, 859-3615, Japan

    Yasuhiro Maeda, Osamu Higuchi & Shunya Nakane

  7. Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan

    Yasuhiro Maeda, Hidenori Matsuo & Shunya Nakane

  8. Department of Child Neurology, Seirei Hamamatsu General Hospital, Shizuoka, Japan

    Tohru Okanishi

  9. Department of Neurology, Kagawa University Hospital, Kagawa, Japan

    Yohei Kokudo & Kazushi Deguchi

  10. Department of Gastroenterology and Hepatology, Nagasaki Kawatana Medical Center, Nagasaki, Japan

    Toshihito Ueki

  11. Department of Neurology, Wakayama Medical University, Wakayama, Japan

    Ken-ya Murata

  12. Department of Medicine and Rheumatology, Okinawa Chubu Hospital, Uruma, Okinawa, Japan

    Takeshi Yoshida & Mistuyo Kinjo

Authors
  1. Akihiro Mukaino
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  2. Hitomi Minami
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  3. Hajime Isomoto
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  4. Hitomi Hamamoto
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  5. Eikichi Ihara
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  6. Yasuhiro Maeda
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  7. Osamu Higuchi
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  9. Yohei Kokudo
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  13. Ken-ya Murata
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  14. Takeshi Yoshida
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  16. Yoshihiro Ogawa
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  18. Hidenori Matsuo
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  19. Kazuhiko Nakao
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  20. Shunya Nakane
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Contributions

Conceived and designed the experiments: AM, HM (Hitomi Minami), HI, OH, HM (Hidenori Matsuo), KN, SN. Performed the experiments: AM, YM, OH. Collected the samples and summarized the cases: AM, HM (Hitomi Minami), HI, HH, EI, TO, YK, KD, FS, TU, KM, TY, KM, YO, AI, KN. Analyzed the data: AM, HM (Hitomi Minami), HI, HH, OH, SN. Wrote the paper: AM, HM (Hitomi Minami), HI, OH, AI, HM (Hidenori Matsuo), KN, SN.

Corresponding author

Correspondence to Shunya Nakane.

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None of the authors have any conflicts of interest to disclose.

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Mukaino, A., Minami, H., Isomoto, H. et al. Anti-ganglionic AChR antibodies in Japanese patients with motility disorders. J Gastroenterol 53, 1227–1240 (2018). https://doi.org/10.1007/s00535-018-1477-8

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  • DOI: https://doi.org/10.1007/s00535-018-1477-8

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