Primary and Acquired Immunodeficiencies Associated With Severe Varicella-Zoster Virus Infections. (28th August 2020)

• Record Type: Journal Article
• Authors: Ansari, Rahila; Rosen, Lindsey B; Lisco, Andrea; Gilden, Don; Holland, Steven M; Zerbe, Christa S; Bonomo, Robert A; Cohen, Jeffrey I
• Is Part Of: Clinical infectious diseases. Volume 73:Number 9(2021)
• Page Start: e2705
• Page End: e2712
• Publication Date: 2020-08-28
• Subjects: varicella-zoster -- immunodeficiency -- zoster -- chickenpox -- interferon; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa1274
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: Although most cases of varicella or zoster are self-limited, patients with certain immune deficiencies may develop severe or life-threatening disease. Methods: We studied a patient with varicella-zoster virus (VZV) central nervous system (CNS) vasculopathy and as part of the evaluation, tested his plasma for antibodies to cytokines. We reviewed the literature for cases of varicella or zoster associated with primary and acquired immunodeficiencies. Results: We found that a patient with VZV CNS vasculopathy had antibody that neutralized interferon (IFN)-α but not IFN-γ. The patient's plasma blocked phosphorylation in response to stimulation with IFN-α in healthy control peripheral blood mononuclear cells. In addition to acquired immunodeficiencies like human immunodeficiency virus (HIV) or autoantibodies to IFN, variants in specific genes have been associated with severe varicella and/or zoster. Although these genes encode proteins with very different activities, many affect IFN signaling pathways, either those that sense double-stranded RNA or cytoplasmic DNA that trigger IFN production, or those involved in activation of IFN stimulated genes in response to binding of IFN with its receptor. Conclusions: Immune deficiencies highlight the critical role of IFN in control of VZV infections and suggest new approaches for treatment of VZV infection in patients with certain immune deficiencies. Abstract : Although numerous primary and acquired immunodeficiencies have been identified that predispose to severe varicella-zoster virus infections, most of these reflect either global defects in cellular immunity or impairment in the interferon signaling pathway.