Impaired HVJ-stimulated Interferon producing capacity in MPO-ANCA-associated vasculitis with rapidly progressive glomerulonephritis lead to susceptibility to infection. (December 2020)

• Record Type: Journal Article
• Authors: Uno, Kazuko; Muso, Eri; Ito-Ihara, Toshiko; Endo, Tomomi; Yasuda, Yuko; Yagi, Katusmi; Suzuki, Kazuo
• Is Part Of: Cytokine. Volume 136(2020)
• Publication Date: 2020-12
• Subjects: MPO-ANCA RPGN -- HVJ-stimulated Interferon producing capacity -- Plasmacytoid dendritic cells -- Susceptibility to infection; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155221
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: MPO-ANCA-RPGN patients show impaired HVJ-stimulated Interferon producing capacity. Patients' low HVJ-stimulated Interferon producing capacity is partially a result of impaired plasamacytoid DC number. Impaired HVJ-stimulated Interferon producing capacity might have resulted from previous bouts of infection. Impaired HVJ-stimulated Interferon producing capacity is responsible for patients' vulnerability to infection. Abstract: ANCA-associated RPGN leads to renal failure through systemic vasculitis and diffuse crescentic glomerulonephritis. MPO-ANCA-RPGN patients are highly susceptible to infections. Our aim in this study was to uncover reasons why these patients were susceptible to infections. We analyzed various aspects of type I interferon system including HVJ-stimulated IFN-α producing capacity and plasmacytoid dendritic cell (pDC) number in whole blood in MPO-ANCA-RPGN patients. Compared with healthy subjects, MPO-ANCA-RPGN patients showed impaired HVJ-stimulated IFN-α producing capacity and lower pDC number with or without glucocorticoid treatment. Immuno-histological staining of MPO-ANCA-RPGN kidney samples revealed a few but apparent pDC in T cell infiltrating regions even in patients with low pDC number in their peripheral blood. Patients' low HVJ-stimulated IFN-α producing capacity and pDC numbers persisted even after patients underwent several years of treatment. Former infection was determined using patients' serum BPI, Lamp-2 and Calprotectin, since they are reflective of a history of infection. These markers were higher in MPO-ANCA-RPGN patients than in healthy subjects. These results indicate that impaired HVJ-stimulated IFN-α production as well as dysfunction of the IFN system might have resulted from a previous bout of infection and can be partially implicated in patients' long-term susceptibility and vulnerability to infection.