Abstract: FR-PO038

Dysregulated Neutrophil Extracellular Traps in a Patient with Propylthiouracil-Induced Microscopic Polyangiitis

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Watanabe, Kanako, Hokkaido University Hospital, Sapporo, Japan
  • Nakazawa, Daigo, Hokkaido University Hospital, Sapporo, Japan
  • Nishio, Saori, Hokkaido University Hospital, Sapporo, Japan
  • Atsumi, Tatsuya, Hokkaido University Hospital, Sapporo, Japan
Background

Neutrophil extracellular traps (NETs) are one of the immune defense system, which spread out DNA fibers with histons and myeloperoxidase (MPO) after phagocytosis in order to trap and kill microbes effectively. However, when NETs are not properly regulated, they could possibly become autoantigens, which result in the production of myeloperoxidase-anti-neutrophil cytoplasmic antibodies (MPO-ANCA), developing Microscopic polyangiitis (MPA). Propylthiouracil (PTU) is an antithyroid drug, clinically known to produce MPO-ANCA and develop MPA. A recent study showed that in vitro experiment neutrophils with PTU were induced to morphologically-abnormal NETs, which were hardly degraded by DNaseI. In Rat model, dysregulated NETs led to the production of MPO-ANCA, causing pulmonary capillaritis and glomerulonephritis. In this report, we examined whether neutrophils of a patient with PTU-induced MPA show the similar characterization during NETs formation.

Methods

A 19-year-old woman who had been treated with PTU for Graves’ disease showed the presence of high fever and arthritis. Increased levels of proteinuria, hematuria, and C-reactive protein were found. In immunological examination, MPO-ANCAs were detected. Computed tomography revealed pulmonary infiltrates. Based on these findings, the patient was diagnosed with PTU-induced MPA. For evaluating NETs formation, we analyzed neutrophils of this patient. The fluorescence microscopy revealed NETs formation in unstimulated neutrophils of the patient, which was more massive in phorbol myristate acetate-stimulated neutrophils. Furthermore, they were not degraded by DNaseI, which can degrade the NET-DNA. On the other hand, the healthy NETs were degraded by DNaseI.

Conclusion

This is the first case report showing that abnormal and dysregulated NETs persisted in a PTU-induced MPA patient. These results indicate that dysregulated NETs can lead to the breakdown of immunological tolerance for NETs components and result in the production of autoantibody for NETs, developing autoimmune vasculitis.