TY - JOUR
T1 - Urine eosinophil-derived neurotoxin
T2 - A potential marker of activity in select eosinophilic disorders
AU - Makiya, Michelle A.
AU - Khoury, Paneez
AU - Kuang, Fei Li
AU - Mata, Alexis Dominique
AU - Mahmood, Sana
AU - Bowman, Abbie
AU - Espinoza, David
AU - Kovacs, Nicholas
AU - Brown, Thomas
AU - Holland, Nicole
AU - Wetzler, Lauren
AU - Ware, Jean Anne M.
AU - Dyer, Anne Marie
AU - Akuthota, Praveen
AU - Bochner, Bruce S.
AU - Chinchilli, Vernon M.
AU - Gleich, Gerald J.
AU - Langford, Carol
AU - Merkel, Peter A.
AU - Specks, Ulrich
AU - Weller, Peter F.
AU - Wechsler, Michael E.
AU - Prussin, Calman
AU - Fay, Michael P.
AU - Klion, Amy D.
N1 - Publisher Copyright:
© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
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U2 - 10.1111/all.15481
DO - 10.1111/all.15481
M3 - Article
C2 - 35971862
AN - SCOPUS:85137233316
SN - 0105-4538
VL - 78
SP - 258
EP - 269
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 1
ER -