Dataset Information

CD14 down-modulation as a real-time biomarker in Kawasaki disease.

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.

SUBMITTER: Inada Y

PROVIDER: S-EPMC10757666 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

CD14 down-modulation as a real-time biomarker in Kawasaki disease.

Inada Yutaro Y Sonoda Motoshi M Mizuno Yumi Y Yamamura Kenichiro K Motomura Yoshitomo Y Takuma Aoba A Murata Kenji K Furuno Kenji K Tezuka Junichiro J Sakai Yasunari Y Ohga Shouichi S Kishimoto Junji J Hosaka Koki K Sakata Satomi S Hara Toshiro T

Clinical & translational immunology 20231230 1

<h4>Objectives</h4>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.<h4>Methods</h4>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 o ...[more]

PMID: 38162960

Similar Datasets

Project description:Background: Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. Results: In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and CD8+ lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Conclusions: Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses. Whole blood (PAXgene tubes) was obtained from 64 Kawasaki disease patients prior to treatment. RNA was amplified using the MessageAmp kit (Ambion), and reverse transcribed. Each sample was labelled with Cy5, and hybridized to a Lymphochip cDNA array along with amplified human reference RNA labelled with Cy3(Universal Human Reference RNA, Stratagene). Analysis was restricted to those array elements (LUIDs) with signal intensity/background of at least 2.5 in either channel for at least 80% of the samples, and a regression correlation of 0.6. Patterns of gene expression were correlated with clinical parameters, including subsequent response to treatment with intravenous immunoglobulin (IVIG). A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Phenotype: Patient responded (R) or not (NR) to IVIG therapy. Some patients were not classified because they were treated more than 10 days after onset of fever Keywords: disease_state_design

Dataset Information

CD14 down-modulation as a real-time biomarker in Kawasaki disease.

Objectives

Methods

Results

Conclusion

Publications

CD14 down-modulation as a real-time biomarker in Kawasaki disease.

Similar Datasets

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