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

Abstract

Objectives: Intravenous immunoglobulin (IVIG) therapy is effective against some autoimmune diseases. We examined the effects of pharmaceutical immunoglobulins on the development of MPO-ANCA-associated vasculitis (MPO-AAV).Methods: Peripheral blood neutrophils were pretreated with 5 mg/ml sulfo-immunoglobulins (IVIG-S) and then exposed to 100 nM phorbol myristate acetate (PMA). Thereafter, neutrophil extracellular traps (NETs) were detected by 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 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: IVIG-S reduce NET formation and ameliorate the development of MPO-AAV.