Linkage of serum ITIH4 with Th2 signature cytokine, inflammation, exacerbation risk and severity in childhood asthma

Abstract

Aim: ITIH4 has anti-inflammatory properties toward eosinophilic/neutrophilic inflammation. This study aimed to explore clinical value of ITIH4 in childhood asthma. Materials & methods: Serum ITIH4 and inflammatory cytokines were determined in 120 childhood asthma patients by enzyme-linked immunosorbent assay. Results: In the entire and acute exacerbation patients, ITIH4 positively associated with IFN-γ, but negatively related to proinflammatory cytokines. ITIH4 was lowest in patients with acute exacerbation, followed by chronic persistent, and highest in clinical remission. By receiver-operating characteristic analysis, ITIH4 potentially estimated acute exacerbation asthma risk. Moreover, ITIH4 negatively related to exacerbation severity in acute exacerbation patients. Conclusion: Serum ITIH4 negatively links with Th2 cell signature cytokine, proinflammatory cytokines, exacerbation risk and severity in childhood asthma.

Article highlights

Introduction

• Asthma exacerbates recurrently in some children and adversely impacts their daily life, therefore, exploring some inflammatory biomarkers to estimate exacerbation risk and severity is clinically meaningful.

• ITIH4 serves as an anti-inflammatory biomarker, while its role in reflecting inflammation as well as the risk and severity of exacerbation in asthma is not identified.

• This prospective study aimed to evaluate the association of serum ITIH4 with multiple inflammatory cytokines, asthma phase and exacerbation severity in childhood asthma patients.

Materials & methods

• A total of 120 childhood asthma patients and 20 healthy subjects were enrolled, whose serum samples were collected after enrollment to detect ITIH4 by enzyme-linked immunosorbent assay (ELISA). Meanwhile, inflammatory cytokines, including IFN-γ, IL-4, TNF-α, IL-1β and IL-8, were also determined in childhood asthma patients via ELISA.

Results

• Serum ITIH4 expression was reduced in childhood asthma patients compared with healthy subjects.

• In the entire childhood asthma patients and those at acute exacerbation phase, ITIH4 was positively linked with IFN-γ and negatively related to IL-4, TNF-α, IL-1β and IL-8.

• In childhood asthma patients at chronic persistent phase, ITIH4 was only negatively linked with IL-4, TNF-α and IL-1β

• In childhood asthma patients at clinical remission phase, no correlation was observed in ITIH4 with these inflammatory cytokines.

• Serum ITIH4 was lowest in patients at acute exacerbation phase, followed by those at chronic persistent phase, and highest in patients at clinical remission phase, which exerted a good ability to differentiate patients at acute exacerbation phase from those at chronic persistent or clinical remission phase.

• In childhood asthma patients at acute exacerbation phase, serum ITIH4 was negatively correlated with exacerbation severity.

Conclusion

• To sum up, serum ITIH4 negatively links with T-helper 2 cell signature cytokine, proinflammatory cytokines, exacerbation risk and severity in childhood asthma.

Keywords: :

• Childhood asthma
• exacerbation risk
• exacerbation severity
• inflammatory cytokines
• ITIH4

Author contributions

W Li: Conceptualization, data curation, formal analysis, project administration, resources, writing – original draft, writing – review & editing. X Wang: Data curation, resources, investigation, writing – original draft, writing – review & editing. H An: Conceptualization, formal analysis, methodology, supervision, Writing – original draft, writing – review & editing.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval (Ethics Committee of the Xingtai People’s Hospital [approval No. 2022032]) and/or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.