PO:35:220 | IgG anti-pentraxin 3 autoantibodies distinguish eosinophilic granulomatosis with polyangiitis from severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps

Eleonora Fiorin¹, Anna Ghirardello¹, Federica Davanzo¹, Luca Iorio¹, Marta Codirenzi¹, Roberta Prevedello¹, Roberto Padoan¹, Andrea Doria¹. | ¹Università di Padova, Dipartimento di Medicina DIMED, UOC di Reumatologia, Padova, Italy.

Background. Eosinophilic granulomatosis with polyangiitis (EGPA) typically presents with severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP), often preceding systemic vasculitis by years. Early identification of patients likely to develop EGPA among those with asthma and sinusitis is therefore crucial. Circulating IgG autoantibodies against Pentraxin-3 (PTX3) have recently been reported in EGPA, raising the possibility that they could help distinguish EGPA from related airway disorders. The objective of the study was to determine the prevalence of anti-PTX3 autoantibodies in patients with EGPA, SEA and CRSwNP, and to evaluate their utility as a biomarker for differentiating EGPA from these conditions.

Materials and Methods. We performed a single-center study including consecutive patients diagnosed with EGPA, and patients with SEA or CRSwNP. Serum anti-PTX3 IgG levels were measured using a standardized, in-house ELISA (positivity cut-off: optical density > 0.234 at 405 nm), as previously described. Liquid-phase inhibition assays were performed to evaluate potential assay interferences. Categorical variables were compared with ² tests; continuous variables with the Mann–Whitney U test.

Results. We included 120 patients diagnosed with EGPA (56.7% female, median age 61), 60 with SEA (68.3% female, median age 59), and 63 with CRSwNP (44.4% female, median age 58). Anti-PTX3 autoantibodies were detected in 35% EGPA patients, compared to 8.3% in asthma and 7.9% in CRSwNP (p<0.001 for EGPA vs each comparator). Median OD values were higher in EGPA (0.175) than in asthma (0.11, p=0.014) and CRSwNP patients (0.07, p=0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner. No associations were found with ANCA status or clinical features at diagnosis. At the time of sample collection, 10% (12/120) of patients were characterized by active disease, while 90% (108/120) experienced remission. No statistically significant differences in the median OD of anti-PTX3 were found based on clinical activity.

Conclusions. IgG anti-PTX3 autoantibodies are significantly more common in EGPA than in SEA or CRSwNP and represent a promising biomarker for early diagnosis. Their detection is independent of ANCA status, and they could help bridge the diagnostic gap in patients with overlapping features.