Pharmaceutical immunoglobulins reduce neutrophil extracellular trap formation and ameliorate the development of MPO-ANCA-associated vasculitis

• Uozumi, Ryo

• Iguchi, Risa

• Masuda, Sakiko

• Nishibata, Yuka

• Nakazawa, Daigo

• Tomaru, Utano

• Ishizu, Akihiro

Abstract

Objectives: Intravenous immunoglobulin (IVIG) therapy is effective against some autoimmune diseases. Although its efficacy on peripheral neuropathy due to eosinophilic granulomatosis with polyangiitis-one of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis (MPO-AAV)-has been established, that on other MPO-AAV remains undetermined. We examined the effects of pharmaceutical immunoglobulins on the formation of neutrophil extracellular traps (NETs) related to MPO-ANCA production and the development of MPO-AAV. Methods: Peripheral blood neutrophils from healthy volunteers were pretreated with 5 mg/ml human sulfo-immunoglobulins (IVIG-S) and then exposed to 100 nM phorbol myristate acetate (PMA). Thereafter, neutrophils were stained with SYTOX Green and then subjected to flow cytometry. Next, Wistar-Kyoto rats were given oral administration of 10 mg/kg/day propylthiouracil for 28 days and intraperitoneal (i.p.) injection of 1 µg PMA on days 0 and 7. These rats were divided into two groups: Group 1 with i.p. injection of 400 mg/kg IVIG-S on days 8-12 and Group 2 with i.p. injection of vehicle similarly. ANCA titers were chronologically determined by indirect immunofluorescence. On day 28, all rats were killed to examine NET formation in the peritoneum and the development of AAV. Results: IVIG-S significantly inhibited NET formation induced by PMA in vitro. NET amounts in the peritoneum in Group 1 were significantly smaller than in Group 2, and ANCA titers in Group 1 were significantly lower than in Group 2. The degree of pulmonary hemorrhage in Group 1 was also smaller than in Group 2. Conclusion: Pharmaceutical immunoglobulins reduce NET formation and ameliorate the development of MPO-AAV.

Journal

• Modern Rheumatology

  Modern Rheumatology 30 (3), 544-550, 2019-04-12

  Taylor & Francis

Keywords

• ANCA-associated vasculitis
• Animal model
• Anti-neutrophil cytoplasmic antibody (ANCA)
• Intravenous immunoglobulin (IVIG)
• Neutrophil extracellular traps (NETs)

Details

• CRID: 1050003824786997120
• NII Article ID: 120006844531
• NII Book ID: AA1157187X
• DOI: 10.1080/14397595.2019.1602292
• ISSN: 14397609
• ISSN: 14397595
• HANDLE: 2115/78182
• Web Site: https://www.tandfonline.com/doi/pdf/10.1080/14397595.2019.1602292
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN