A novel assay for improved detection of sputum periostin in patients with asthma

Serum periostin associates with type-2 inflammation in asthmatic airways, but also reflects whole body periostin levels originating from multiple sources. Less is known about sputum periostin as a biomarker in asthma as detection levels are low using currently available periostin assays. We aimed to...

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Bibliographic Details
Published in:PloS one 2023-02, Vol.18 (2), p.e0281356-e0281356
Main Authors: Ono, Junya, Takai, Masayuki, Kamei, Ayami, Ohta, Shoichiro, Nair, Parameswaran, Izuhara, Kenji, Dahlén, Sven-Erik, James, Anna
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Antibodies
Antigenic determinants
Assaying
Asthma
Asthma - drug therapy
Biological markers
Biological products
Biology and Life Sciences
Biomarkers
Care and treatment
Cleavage
Diagnosis
Enzyme-linked immunosorbent assay
Eosinophils
Epitopes
Ethylenediaminetetraacetic acid
Health aspects
Humans
Inflammation
Interleukin 13
Leukocytes (eosinophilic)
Medicin och hälsovetenskap
Medicine and Health Sciences
Molecular weight
Patients
Peptides
Pharmaceutical industry
Phenotype
Phenotypes
Proteins
Proteolysis
Research and Analysis Methods
Respiratory function
Sputum
Sputum - chemistry
Viral antibodies
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Summary:Serum periostin associates with type-2 inflammation in asthmatic airways, but also reflects whole body periostin levels originating from multiple sources. Less is known about sputum periostin as a biomarker in asthma as detection levels are low using currently available periostin assays. We aimed to investigate detection of sputum periostin using ELISA assays targeting different periostin epitopes and relate levels to clinical characteristics. Two ELISA systems were developed using antibodies detecting whole periostin or cleavage products, the molecular weight and amino acid sequences of which were confirmed. The ELISA assays were applied to sputum from 80 patients with mild-to-moderate and severe asthma enrolled in the European, multi-center study BIOAIR. Results were related to clinical characteristics. Sputum was found to contain smaller periostin fragments, possibly due to proteolytic cleavage at a C-terminal site. Comparing ELISA methodology using antibodies against cleaved versus whole periostin revealed detectable levels in 90% versus 44% of sputum samples respectively. Sputum periostin showed associations with blood and sputum eosinophils. Furthermore, sputum, but not serum, periostin correlated with reduced lung function and sputum IL-13 and was reduced by oral corticosteroid treatment. We present an ELISA method for improved analysis of sputum periostin by detecting cleavage products of the periostin protein. Using this assay, sputum periostin was detectable and associated with more disease-relevant parameters in asthma than serum periostin. Sputum periostin is worth considering as a phenotype-specific biomarker in asthma as its proximity to the airways may eliminate some of the confounding factors known to affect serum periostin.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0281356