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

• Published in: Cytokine (Philadelphia, Pa.) Vol. 136; p. 155221
• Main Authors: Uno, Kazuko, Muso, Eri, Ito-Ihara, Toshiko, Endo, Tomomi, Yasuda, Yuko, Yagi, Katusmi, Suzuki, Kazuo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2020
• Subjects: HVJ-stimulated Interferon producing capacity; MPO-ANCA RPGN; Plasmacytoid dendritic cells; Susceptibility to infection; Plasmacytoid dendritic cells; Susceptibility to infection; MPO-ANCA RPGN; HVJ-stimulated Interferon producing capacity
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2020.155221

•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. 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.