CD14 Down-modulation As a Real-time Biomarker in Kawasaki Disease

Overview

Journal Clin Transl Immunology

Specialty Allergy & Immunology

Date 2024 Jan 1

PMID 38162960

Authors

Yutaro Inada

Motoshi Sonoda

Yumi Mizuno

Kenichiro Yamamura

Yoshitomo Motomura

Aoba Takuma

Kenji Murata

Kenji Furuno

Junichiro Tezuka

Yasunari Sakai

Shouichi Ohga

Junji Kishimoto

Koki Hosaka

Satomi Sakata

Toshiro Hara

Affiliations

Soon will be listed here.

Abstract

Objectives: The objectives of this study were to investigate the pathophysiology of Kawasaki disease (KD) from immunological and oxidative stress perspectives, and to identify real-time biomarkers linked to innate immunity and oxidative stress in KD.

Methods: We prospectively enrolled 85 patients with KD and 135 patients with diverse conditions including immune, infectious and non-infectious diseases for this investigation. Flow cytometry was used to analyse the surface expression of CD14, CD38 and CD62L on monocytes, along with a quantitative assessment of CD14 down-modulation. Additionally, oxidative stress levels were evaluated using derivatives of reactive oxygen metabolites (d-ROMs) and antioxidant capacity measured by a free radical elective evaluator system.

Results: During the acute phase of KD, we observed a prominent CD14 down-modulation on monocytes, reflecting the indirect detection of circulating innate immune molecular patterns. Moreover, patients with KD showed a significantly higher CD14 down-modulation compared with infectious and non-infectious disease controls. Notably, the surface expression of CD14 on monocytes was restored concurrently with responses to intravenous immunoglobulin and infliximab treatment in KD. Furthermore, d-ROM levels in patients with KD were significantly elevated compared with patients with infectious and non-infectious diseases. Following intravenous immunoglobulin treatment, oxidative stress levels decreased in patients with KD.

Conclusion: Monitoring CD14 down-modulation on monocytes in real-time is a valuable strategy for assessing treatment response, distinguishing KD relapse from concomitant infections and selecting second-line therapy after IVIG treatment in KD patients. The interplay between inflammation and oxidative stress likely plays a crucial role in the development of KD.

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