Pulmonary Eosinophilic Granulomatosis with Polyangiitis (EGPA) has Allergic and Immunoregulatory Features

Abstract Introduction Eosinophilic granulomatosis with polyangiitis (EGPA) is a life-threatening vasculitis that can cause heart failure, neuropathy, and organ damage. EGPA is a rare cause of systemic vasculitis, and its prevalence is estimated at 1 in 2 million. The pathophysiology of EGPA is poorly understood. We aim to characterize EGPA lung immunopathologic findings. Methods We studied five open lung biopsies and one transbronchial biopsy of active, untreated EGPA patients and compared them to lung tissue controls. They were studied by histopathology, immunostaining, and RNA sequencing with confirmatory RT-PCR. Results The characteristic parenchymal interstitial infiltrate contains eosinophils, FoxP3+ regulatory T cells (Tregs), abundant macrophages, basophils, mast cells, and many IgG4 plasma cells. IgG4+ granular deposits resembling immune complexes are present focally, some coating macrophages. RNA studies confirm that EGPA lung has abundant IGHG4 (increased 1,885-fold relative to controls, p<2E-15) and, to a lesser degree, other immunoglobulin transcripts. Statistically significant increases, each ≥8-fold greater in EGPA compared to controls, are also seen for SIGLEC8 (for eosinophils), FOXP3, IL13, CCL18, CCL13, B cell markers, CYP27B1 (which makes calcitriol, active vitamin D) and the alternatively activated macrophage marker CD209 (DC-SIGN). Conclusions EGPA has both type 2 and immunoregulatory features. We propose a novel mechanism involving these findings that induces the EGPA immune response.