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

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2024 Oct 25

PMID 39453496

Authors

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

Affiliations

Soon will be listed here.

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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