Immunoglobulin profiling identifies unique signatures in patients with Kawasaki disease during intravenous immunoglobulin treatment

Human Molecular Genetics
Tai-Ming KoYusuke Nakamura

Abstract

Identifying the causes of high fever syndromes such as Kawasaki disease (KD) remains challenging. To investigate pathogen exposure signatures in suspected pathogen-mediated diseases such as KD, we performed immunoglobulin (Ig) profiling using a next-generation sequencing method. After intravenous Ig (IVIG) treatment, we observed disappearance of clonally expanded IgM clonotypes, which were dominantly observed in acute-phase patients. The complementary-determining region 3 (CDR3) sequences of dominant IgM clonotypes in acute-phase patients were commonly observed in other Ig isotypes. In acute-phase KD patients, we identified 32 unique IgM CDR3 clonotypes shared in three or more cases. Furthermore, before the IVIG treatment, the sums of dominant IgM clonotypes in IVIG-resistant KD patients were significantly higher than those of IVIG-sensitive KD patients. Collectively, we demonstrate a novel approach for identifying certain Ig clonotypes for potentially interacting with pathogens involved in KD; this approach could be applied for a wide variety of fever-causing diseases of unknown origin.

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Citations

Feb 20, 2020·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Ling-Sai ChangHo-Chang Kuo
Oct 28, 2020·Journal of Human Genetics·Todd A JohnsonYoshihiro Onouchi
Jun 15, 2021·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Yoichiro Kamatani, Yusuke Nakamura

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