Dynamic Changes in the Nasal Microbiome Associated with Disease Activity in Patients with Granulomatosis with Polyangiitis.

OBJECTIVE Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). We examined longitudinal changes in the nasal microbiome in association with relapse in GPA patients. METHODS Bacterial 16S gene sequencing was performed on nasal swabs of 19 patients with GPA followed longitudinally for a total of 78 visits, including 9 patients who developed a relapse and 10 patients who remained in remission. Relative abundance of bacteria and ratios between bacteria were examined. Generalized estimating equation models evaluated the association between bacterial composition and 1) disease activity and 2) PR3-ANCA level, adjusting for medications. RESULTS Corynebacterium and Staphylococcus were the most abundant bacterial genera across all nasal samples. Patients with quiescent disease maintained a stable ratio of Corynebacterium to Staphylococcus across visits. In contrast, in patients who experienced a relapse, a significantly lower ratio occurred at the visit prior to relapse, followed by a higher ratio at time of relapse (adjusted P < 0.01). Species-level analysis identified an association between higher abundance of nasal Corynebacterium tuberculostearicum and relapse (adjusted P = 0.04) and higher PR3-ANCA levels (adjusted P = 0.02). CONCLUSION In GPA, significant changes occur in the nasal microbiome over time and are associated with disease activity. The occurrence of these changes months prior to onset of relapse supports a pathogenic role of nasal bacteria in GPA. Our results uphold existing hypotheses implicating Staphylococcus as an instigator of disease and have generated a novel finding involving Corynebacterium as a potential mediator of disease in GPA.