IgG anti-Pentraxin 3 antibodies are a novel biomarker of ANCA-associated vasculitis and better identify patients with eosinophilic granulomatosis with polyangiitis

Objective: To investigate prevalence of anti-Pentraxin 3 (PTX3) antibodies in sera of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients.

Methods: Anti-PTX3 and PTX3 levels were analysed by enzyme-linked immunosorbent assays in sera from unselected patients with AAV and compared with patients with systemic lupus erythematosus (SLE, n = 130), other connective tissue diseases (CTDs, n = 97) and matched healthy controls (n = 97). Optical density (OD) cut-off for positive anti-PTX3 antibodies was determined by ROC curve analysis and set as 0.234. Indirect immunofluorescence (IIF) on fixed human granulocytes was used to analyze the fluorescence pattern of anti-PTX3 antibodies. Liquid-phase inhibition tests were conducted to assess potential interferences.

Results: We included 101 AAV patients (females 58%, median age 60[51-69] years) affected either with granulomatosis with polyangiitis (GPA, n = 51), microscopic polyangiitis (MPA, n = 12) or eosinophilic granulomatosis with polyangiitis (EGPA, n = 38). Anti-PTX3 antibodies were detected in 29.7% AAV patients, being significantly higher than in healthy controls (p < 0.001) and CTDs (p = 0.030) but lower than in SLE (p = 0.004). Anti-PTX3 antibody prevalence was 44.7% in EGPA, 25% in MPA and 19% in GPA (p = 0.034). Among ANCA negative patients, 35.7% displayed positive anti-PTX3 antibodies. Anti-PTX3 were associated with a lower prevalence of systemic (p = 0.002), ear-nose-throat (p = 0.006) and renal manifestations (p = 0.016). Anti-PTX3 antibodies were characterized by a specific IIF pattern on fixed granulocytes. PTX3 serum levels resulted lower in AAV than healthy controls (p < 0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner.

Conclusions: Anti-PTX3 autoantibodies appear a promising novel biomarker of AAV, especially EGPA.