Insights from comparison of serum IgG4 between T2-eosinophilic asthma and eosinophilic granulomatosis with polyangiitis/idiopathic hypereosinophilic syndrome

Objective: 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). Conclusion 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.