Defining the Nasal Transcriptome in Granulomatosis with Polyangiitis

Nasal disease occurs in the majority of patients with granulomatosis with polyangiitis (GPA, Wegener’s) and is often a presenting feature of the disease[1]. Features of nasal disease in GPA include obstruction, crusting, ulceration, epistaxis, and cartilaginous/bony destruction with potential resultant saddle nose deformity[2]. The incidence of rhinosinusitis at time of diagnosis is estimated to be 75% in GPA, and 90% of patients with GPA will develop sinonasal disease at some point during the course of disease[1, 3]. For many patients with GPA, localized symptoms of upper airway involvement can precede the development of antineutrophil cytoplasmic antibodies (ANCA) and systemic disease by months to years[4]. There is an unmet need for novel diagnostic biomarkers and markers of nasal disease activity in GPA. When nasal histology for GPA is defined by the presence of small vessel vasculitis, granuloma, or extravascular necrosis, the diagnostic accuracy of nasal biopsies is only approximately 50%[5]. Patients with GPA often report persistent upper airway disease despite treatment and improvement in inflammation in other organ systems. In these settings, distinguishing symptoms of active nasal disease from symptoms related to chronic nasal damage is often challenging. The objective of this study was to characterize the nasal transcriptome in GPA using samples collected with a minimally invasive brushing technique. Whole genome gene expression profiling of nasal brushings was used to identify differentially expressed genes in GPA versus a composite comparator group. Gene sets were identified within subsets of patients with GPA in association with active nasal disease, nasal damage, and independent of nasal disease activity status.