Abstract
Background: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. Methods: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. Results: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. Conclusions: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 258-269 |
| Number of pages | 12 |
| Journal | Allergy: European Journal of Allergy and Clinical Immunology |
| Volume | 78 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2023 |
Funding
C.P. is an employee of Knopp Biosciences and owns stock or stock options in Knopp Biosciences. M.E.W. has received consulting, advisory, or speaking honoraria from the following: Amgen, AstraZeneca, Avalo Therapeutics, Boehringer Ingelheim, Cerecor, Cohero Health, Cytoreason, Eli Lilly, Equillium, Glaxosmithkline, Incyte, Kinaset, Novartis, Phylaxis, Qilu Puget Sound Biotherapeutics, Pulmatrix, Rapt Therapeutics, Regeneron, Restorbio, Roche/Genentech, Sanofi/Genzyme, Sentien, Sound Biologics, Teva, and Upstream Bio. P.A.M. reports receiving funds for the following activities in the past 2 years: (1) Consulting: AbbVie, AstraZeneca, Boeringher‐Ingelheim, Bristol‐Myers Squibb, ChemoCentryx, CSL Behring, Dynacure, EMDSerono, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, Immagene, InflaRx, Jannsen, Kiniksa, Kyverna, Magenta, MiroBio, Mitsubishi, Neutrolis, Novartis, NS Pharma, Pfizer, Regeneron, Sparrow, Takeda, and Talaris. (2) Research Support: AbbVie, AstraZeneca, Boeringher‐Ingelheim, Bristol‐Myers Squibb, ChemoCentryx, Eicos, Electra, Forbius, Genentech/Roche, Genzyme/Sanofi, GlaxoSmithKline, InflaRx, Sanofi, and Takeda. (3) Stock options: Kyverna. (4) Royalties: UpToDate. P.A. declares research support and consulting fees from GlaxoSmithKline, AstraZeneca, and Sanofi, and research support from Regeneron. B.S.B. is supported in part by National Institute of Allergy and Infectious Diseases grants U19 AI136443 and R21 AI159586. He receives publication‐related royalty payments from Elsevier and UpToDate®/Wolters Kluwer, remuneration for consulting services (Third Harmonic Bio, Acelyrin Inc. and Lupagen) and for serving on the scientific advisory board of Allakos Inc. He also owns stock in Allakos. He is a co‐inventor on existing Siglec‐8‐related patents and thus receives royalty payments from Johns Hopkins University during development and potential sales of Siglec‐8 antibody products. P.F.W. has acted as a consultant for GSK and has served on Data and Safety Monitoring Boards for AstraZeneca. All other authors declare that they have no conflict of interest. This study was funded in part by the Division of Intramural Research, NIAID, NIH (AK) and in part by NIAID Grant Number 1 U01 AI097073 (MW).
Keywords
- benralizumab
- eosinophil granule protein
- eosinophilia
- hypereosinophilic syndrome
- mepolizumab
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
