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通过无偏随机肽展示噬菌体筛选,1 型发作性睡病患者中不存在特定的自身抗体。

Absence of specific autoantibodies in patients with narcolepsy type 1 as indicated by an unbiased random peptide-displayed phage screening.

机构信息

Department of Biobank, Hi-Tech Center and Vinmec-VinUni Institute of Immunology, Vinmec Healthcare system, Hanoi, Vietnam.

Department of Neurology, Sleep-Wake Disorder Center, CHU Montpellier, Montpellier, France.

出版信息

PLoS One. 2024 Mar 5;19(3):e0297625. doi: 10.1371/journal.pone.0297625. eCollection 2024.


DOI:10.1371/journal.pone.0297625
PMID:38442093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10914298/
Abstract

Narcolepsy type 1 (NT1) is an enigmatic sleep disorder characterized by the selective loss of neurons producing orexin (also named hypocretin) in the lateral hypothalamus. Although NT1 is believed to be an autoimmune disease, the orexinergic neuron-specific antigens targeted by the pathogenic immune response remain elusive. In this study, we evaluated the differential binding capacity of various peptides to serum immunoglobin G from patients with NT1 and other hypersomnolence complaints (OHCs). These peptides were selected using an unbiased phage display technology or based on their significant presence in the serum of NT1 patients as identified from previous studies. Although the subtractive biopanning strategy successfully enriched phage clones with high reactivity against NT1 serum IgG, the 101 randomly selected individual phage clones could not differentiate the sera from NT1 and OHC. Compared to the OHC control group, serum from several NT1 patients exhibited increased reactivity to the 12-mer peptides derived from TRBV7, BCL-6, NRXN1, RXRG, HCRT, and RTN4 proteins, although not statistically significant. Collectively, employing both unbiased and targeted methodologies, we were unable to detect the presence of specific autoantibodies in our NT1 patient cohort. This further supports the hypothesis that the autoimmune response in NT1 patients likely stems primarily from T cell-mediated immunity rather than humoral immunity.

摘要

发作性睡病 1 型(NT1)是一种神秘的睡眠障碍,其特征是外侧下丘脑产生食欲素(也称为下丘脑分泌素)的神经元选择性丧失。尽管 NT1 被认为是一种自身免疫性疾病,但致病免疫反应针对的食欲素能神经元特异性抗原仍难以捉摸。在这项研究中,我们评估了各种肽与 NT1 患者和其他嗜睡症投诉(OHC)患者血清免疫球蛋白 G 的差异结合能力。这些肽使用无偏噬菌体展示技术选择,或基于它们在 NT1 患者血清中的显著存在,如先前研究中所确定的。尽管减法生物淘选策略成功地富集了对 NT1 血清 IgG 具有高反应性的噬菌体克隆,但 101 个随机选择的单个噬菌体克隆无法区分 NT1 和 OHC 的血清。与 OHC 对照组相比,尽管没有统计学意义,但来自几个 NT1 患者的血清对源自 TRBV7、BCL-6、NRXN1、RXRG、HCRT 和 RTN4 蛋白的 12 肽表现出增加的反应性。总之,我们采用无偏和靶向方法都未能在我们的 NT1 患者队列中检测到特异性自身抗体的存在。这进一步支持了 NT1 患者中的自身免疫反应可能主要源自 T 细胞介导的免疫而不是体液免疫的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/23332e9b97b0/pone.0297625.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/93ffdfd2ff3f/pone.0297625.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/e9482fe40f1c/pone.0297625.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/dc8c063627d9/pone.0297625.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/c6ab05ac689c/pone.0297625.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/23332e9b97b0/pone.0297625.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/93ffdfd2ff3f/pone.0297625.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/e9482fe40f1c/pone.0297625.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/dc8c063627d9/pone.0297625.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/c6ab05ac689c/pone.0297625.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca19/10914298/23332e9b97b0/pone.0297625.g005.jpg

相似文献

[1]
Absence of specific autoantibodies in patients with narcolepsy type 1 as indicated by an unbiased random peptide-displayed phage screening.

PLoS One. 2024

[2]
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[3]
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[4]
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[5]
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[6]
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Nat Commun. 2019-2-19

[7]
Non-invasive detection of narcolepsy type I phenotypical features and disease progression by continuous home-cage monitoring of activity in two mouse models: the HCRT-KO and DTA model.

Sleep. 2023-9-8

[8]
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[9]
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[10]
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Nat Rev Immunol. 2024-1

本文引用的文献

[1]
Oral Orexin Receptor 2 Agonist in Narcolepsy Type 1.

N Engl J Med. 2023-7-27

[2]
The immunopathogenesis of narcolepsy type 1.

Nat Rev Immunol. 2024-1

[3]
Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.

Nat Commun. 2023-5-15

[4]
Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy.

Brain. 2022-6-30

[5]
Tissue-resident CD8 T cells drive compartmentalized and chronic autoimmune damage against CNS neurons.

Sci Transl Med. 2022-4-13

[6]
Autoantibodies in Pandemrix-induced narcolepsy: Nine candidate autoantigens fail the conformational autoantibody test.

Autoimmunity. 2019-7-22

[7]
Narcolepsy - clinical spectrum, aetiopathophysiology, diagnosis and treatment.

Nat Rev Neurol. 2019-7-19

[8]
Identification of Serum Biomarkers for Systemic Lupus Erythematosus Using a Library of Phage Displayed Random Peptides and Deep Sequencing.

Mol Cell Proteomics. 2019-7-15

[9]
CD8 T cells from patients with narcolepsy and healthy controls recognize hypocretin neuron-specific antigens.

Nat Commun. 2019-2-19

[10]
Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy.

Proc Natl Acad Sci U S A. 2018-12-12

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