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

• Published in: Human molecular genetics 2018-08, Vol.27 (15), p.2671-2677
• Main Authors: Ko, Tai-Ming, Kiyotani, Kazuma, Chang, Jeng-Sheng, Park, Jae-Hyun, Yin Yew, Poh, Chen, Yuan-Tsong, Wu, Jer-Yuarn, Nakamura, Yusuke
• Format: Article
• Language: English
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddy176

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.