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

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2024年10月25日

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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

摘要

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.