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Insights from comparison of serum IgG4 between T2-eosinophilic asthma and eosinophilic granulomatosis with polyangiitis/idiopathic hypereosinophilic syndrome
M.A. Piga1, M. Martini2, P. Fraticelli3, M.S. Garritani4, G. Ghirelli5, A. Canalini6, L. Antonicelli7, G.P. Martino8, M. Gallifuoco9, A. Di Vincenzo10, M.C. Braschi11, M.G. Danieli12, M.B. Bilò13, G. Moroncini14
- National PhD Course in Precision Medicine in Rare Diseases, University of Palermo; Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona; and Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona; and Allergy Unit, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Allergy Unit, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona; and Postgraduate School of Internal Medicine, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.
- Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona; and Postgraduate School of Internal Medicine, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.
- Allergy Unit, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Internal Medicine Unit, Hospital Augusto Murri, Fermo, Italy.
- Allergy Unit, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona; and Allergy Unit, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Allergy Unit, Department of Internal Medicine, Marche University Hospital, Ancona, Italy.
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona; Immunologia delle Malattie Rare e dei Trapianti, Department of Internal Medicine, Marche University Hospital, Ancona; and Postgraduate School of Allergy and Clinical Immunology, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona; Allergy Unit, Department of Internal Medicine, Marche University Hospital, Ancona; and Postgraduate School of Allergy and Clinical Immunology, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy. m.b.bilo@staff.univpm.it
- Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona; Clinica Medica, Department of Internal Medicine, Marche University Hospital, Ancona; and Postgraduate School of Internal Medicine, Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.
CER18546
2025 Vol.43, N°4
PI 0710, PF 0717
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PMID: 40201966 [PubMed]
Received: 16/01/2025
Accepted : 10/03/2025
In Press: 08/04/2025
Published: 08/04/2025
Abstract
OBJECTIVES:
Eosinophilic granulomatosis with polyangiitis (EGPA) and idiopathic hypereosinophilic syndrome (iHES) are systemic hypereosinophilic diseases largely overlapping. Type 2 (T2)-eosinophilic asthma is documented in 100% and 44-95% of EGPA and iHES patients, respectively, probably representing the beginning of the systemic eosinophilic disorders, as suggested by mepolizumab, effective in both asthma and EGPA/iHES. In this respect, there are no predictive biomarkers of progression from T2-eosinophilic asthma into EGPA/iHES. Immunoglobulins G type 4 (IgG4) take part in T2-eosinophilic inflammation, and elevated serum IgG4 have been previously documented in asthma, EGPA and HES. The objective of this study was to compare serum IgG4 between T2-eosinophilic asthma and EGPA/iHES in order to identify significant differences that could represent a reasonable background for prospective studies on IgG4 as potential predictive biomarker of progression from asthma to EGPA/iHES.
METHODS:
In this retrospective/cross-sectional case-control study, patients affected by T2-eosinophilic asthma or EGPA/iHES were consecutively enrolled. All patients underwent blood tests for serum IgG4. Asthmatics and EGPA/iHES patients were stratified upon serum IgG4 values (normal or elevated).
RESULTS:
62 patients were enrolled (27 asthmatics, 35 EGPA/iHES). The frequency of patients with elevated serum IgG4 was higher in the EGPA/iHES group than in the asthmatics (45.7% vs. 11.1%, p=0.003), as well as the mean serum IgG4 value (p=0.010).
CONCLUSIONS:
Elevated serum IgG4 seemed to discriminate between T2-eosinophilic asthma “alone” and T2-eosinophilic asthma evolved into EGPA/iHES. This finding could represent a reasonable background for prospective long-term studies on asthmatic naive patients aimed at investigating IgG4 as a potential predictive biomarker of progression from asthma to EGPA/iHES.
