A Non-targeted Proteomics Newborn Screening Platform for Inborn Errors of Immunity.

IF 7.2 2区医学 Q1 IMMUNOLOGY Journal of Clinical Immunology Pub Date : 2024-10-25 DOI:10.1007/s10875-024-01821-7

Hirofumi Shibata, Daisuke Nakajima, Ryo Konno, Atsushi Hijikata, Motoko Higashiguchi, Hiroshi Nihira, Saeko Shimodera, Takayuki Miyamoto, Masahiko Nishitani-Isa, Eitaro Hiejima, Kazushi Izawa, Junko Takita, Toshio Heike, Ken Okamura, Hidenori Ohnishi, Masataka Ishimura, Satoshi Okada, Motoi Yamashita, Tomohiro Morio, Hirokazu Kanegane, Kohsuke Imai, Yasuko Nakamura, Shigeaki Nonoyama, Toru Uchiyama, Masafumi Onodera, Ryuta Nishikomori, Osamu Ohara, Yusuke Kawashima, Takahiro Yasumi

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Abstract

Purpose: Newborn screening using dried blood spot (DBS) samples for the targeted measurement of metabolites and nucleic acids has made a substantial contribution to public healthcare by facilitating the detection of neonates with genetic disorders. Here, we investigated the applicability of non-targeted quantitative proteomics analysis to newborn screening for inborn errors of immunity (IEIs).

Methods: DBS samples from 40 healthy newborns and eight healthy adults were subjected to non-targeted proteomics analysis using liquid chromatography-mass spectrometry after removal of the hydrophilic fraction. Subsequently, DBS samples from 43 IEI patients were analyzed to determine whether patients can be identified by reduced expression of disease-associated proteins.

Results: DBS protein profiling allowed monitoring of levels of proteins encoded by 2912 genes, including 1110 listed in the Online Mendelian Inheritance in Man database, in healthy newborn samples, and was useful in identifying patients with IEIs by detecting reduced levels of disease causative proteins and their interacting proteins, as well as cell-phenotypical alterations.

Conclusion: Our results indicate that non-targeted quantitative protein profiling of DBS samples can be used to identify patients with IEIs and develop a novel newborn screening platform for genetic disorders.

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先天性免疫错误的非靶向蛋白质组学新生儿筛查平台。

目的：利用干血斑（DBS）样本对代谢物和核酸进行靶向测量的新生儿筛查有助于发现患有遗传性疾病的新生儿，从而为公共医疗保健做出了巨大贡献。在此，我们研究了非靶向定量蛋白质组学分析在新生儿先天性免疫错误（IEIs）筛查中的适用性：方法：40 名健康新生儿和 8 名健康成人的 DBS 样品在去除亲水部分后，采用液相色谱-质谱法进行了非靶向蛋白质组学分析。随后，对 43 名 IEI 患者的 DBS 样本进行了分析，以确定是否可以通过疾病相关蛋白表达的减少来识别患者：DBS蛋白质分析可监测健康新生儿样本中2912个基因编码的蛋白质水平，其中1110个基因被列入在线人类孟德尔遗传数据库，通过检测致病蛋白质及其相互作用蛋白质水平的降低以及细胞表型的改变，DBS蛋白质分析有助于识别IEI患者：我们的研究结果表明，对 DBS 样本进行非靶向定量蛋白质分析可用于识别 IEI 患者，并开发出一种新型的新生儿遗传疾病筛查平台。

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来源期刊

Journal of Clinical Immunology 医学-免疫学

CiteScore

12.20

自引率

9.90%

发文量

218

审稿时长

2 months

期刊介绍： The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.