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神经性厌食症中的抗下丘脑自身抗体:神经生理紊乱的一种新的可能机制?

Anti-hypothalamus autoantibodies in anorexia nervosa: a possible new mechanism in neuro-physiological derangement?

机构信息

Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, 16132, Genoa, Italy.

IRCCS Ospedale Policlinico San Martino, 16132, Genoa, Italy.

出版信息

Eat Weight Disord. 2022 Oct;27(7):2481-2496. doi: 10.1007/s40519-022-01388-5. Epub 2022 Mar 16.

DOI:10.1007/s40519-022-01388-5
PMID:35297008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9556421/
Abstract

PURPOSE

Anorexia nervosa (AN) is a serious and complex mental disorder affecting mainly young adult women. AN patients are characterized by low body weight in combination with self-induced starvation, intense fear of gaining weight, and distortion of body image. AN is a multifactorial disease, linked by recent evidence to a dysregulation of the immune system.

METHODS

In this pilot study, 22 blood serums from AN patients were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. Cellular fluorescence suggests the presence of autoantibodies which are able to recognize these neurons (both to body cell and fiber levels). By means of ELISA, these autoantibodies are quantitatively evaluated. In addition, orexigenic and anorexigenic molecules were measured by ELISA. As control, 18 blood serums from healthy age matched woman were analysed.

RESULTS

All AN patients showed a reactivity against hypothalamic neurons both by immunofluorescence and ELISA. In addition, ghrelin, pro-opiomelanocortin (POMC), and agouti-related peptide (AGRP) were significantly higher than in control serums (p < 0.0001). In contrast, leptin was significantly lower in AN patients than controls (p < 0.0001).

CONCLUSIONS

Immunoreaction and ELISA assays on AN blood serum suggest the presence of autoantibodies AN related. However, it is not easy to determine the action of these antibodies in vivo: they could interact with specific ligands expressed by hypothalamic cells preventing their physiological role, however, it is also possible that they could induce an aspecific stimulation in the target cells leading to an increased secretion of anorexigenic molecules. Further studies are needed to fully understand the involvement of the immune system in AN pathogenesis.

LEVEL OF EVIDENCE

V, descriptive study.

摘要

目的

神经性厌食症(AN)是一种严重且复杂的精神障碍,主要影响年轻成年女性。AN 患者的特征是体重过低,伴有自我饥饿、强烈的体重增加恐惧和身体形象扭曲。AN 是一种多因素疾病,最近的证据表明与免疫系统失调有关。

方法

在这项初步研究中,通过免疫荧光和自制 ELISA 检测,对 22 份 AN 患者的血液血清进行了针对灵长类下丘脑室旁神经元的自身抗体检测。细胞荧光表明存在能够识别这些神经元的自身抗体(体细胞核和纤维水平)。通过 ELISA 定量评估这些自身抗体。此外,还通过 ELISA 测量了食欲促进和食欲抑制分子。作为对照,分析了 18 份来自健康年龄匹配女性的血液血清。

结果

所有 AN 患者在免疫荧光和 ELISA 检测中均显示对下丘脑神经元的反应。此外,ghrelin、pro-opiomelanocortin(POMC)和 agouti-related peptide(AGRP)明显高于对照血清(p < 0.0001)。相反,瘦素在 AN 患者中明显低于对照组(p < 0.0001)。

结论

对 AN 血清的免疫反应和 ELISA 检测表明存在与 AN 相关的自身抗体。然而,很难确定这些抗体在体内的作用:它们可能与下丘脑细胞表达的特定配体相互作用,阻止其生理作用,但也可能导致靶细胞的非特异性刺激,从而导致食欲抑制分子的分泌增加。需要进一步研究才能充分了解免疫系统在 AN 发病机制中的作用。

证据水平

V,描述性研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/1df96c9dcb1e/40519_2022_1388_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/1dda7372cb22/40519_2022_1388_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/e0791e1a7d25/40519_2022_1388_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/60f84046beeb/40519_2022_1388_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/180d8acd6a85/40519_2022_1388_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/7f8e19ad169a/40519_2022_1388_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/88b07d23ba01/40519_2022_1388_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/760a37a96720/40519_2022_1388_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/1df96c9dcb1e/40519_2022_1388_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/1dda7372cb22/40519_2022_1388_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/e0791e1a7d25/40519_2022_1388_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/60f84046beeb/40519_2022_1388_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/180d8acd6a85/40519_2022_1388_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/7f8e19ad169a/40519_2022_1388_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/88b07d23ba01/40519_2022_1388_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/760a37a96720/40519_2022_1388_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb1/9556421/1df96c9dcb1e/40519_2022_1388_Fig8_HTML.jpg

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