tetano
Editor, Senior Moderator
FEBS J
. 2021 May 10.
doi: 10.1111/febs.15961. Online ahead of print.
Infection-induced inflammation from specific inborn errors of immunity to COVID-19
Cheng-Lung Ku[SUP] 1 2 [/SUP], I-Ting Chen[SUP] 3 [/SUP], Ming-Zong Lai[SUP] 3 [/SUP]
Affiliations
Abstract
Inborn error of immunity (IEIs) are a group of genetically-defined disorders leading to defective immunity. Some IEIs have been linked to mutations of immune receptors or signaling molecules, resulting in defective signaling of respective cascades essential for combating specific pathogens. However, it remains incompletely understood why in selected IEIs, such as X-linked lymphoproliferative syndrome type-2 (XLP-2), hypo-immune response to specific pathogens results in persistent inflammation. Moreover, mechanisms underlying the generation of anti-cytokine autoantibodies are mostly unknown. Recently, IEIs have been associated with coronavirus disease 2019 (COVID-19), with a small proportion of patients that contract severe COVID-19 displaying loss-of-function mutations in genes associated with type I interferons (IFNs). Moreover, approximately 10% of patients with severe COVID-19 possess anti-type I IFN neutralizing autoantibodies. Apart from IEIs that impair immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV-2 encodes several proteins that suppress early type I IFN production. One primary consequence of the lack of type I IFNs during early SARS-CoV-2 infection is the increased inflammation associated with COVID-19. In XLP-2, resolution of inflammation rescued experimental subjects from infection-induced mortality. Recent studies also indicate that targeting inflammation could alleviate COVID-19. In this review, we discuss infection-induced inflammation in IEIs, using XLP-2 and COVID-19 as examples. We suggest that resolving inflammation may represent an effective therapeutic approach to these diseases.
Keywords: COVID-19; Inborn errors of immunity; SARS-CoV-2; XLP-2; anti-cytokine autoantibodies.
. 2021 May 10.
doi: 10.1111/febs.15961. Online ahead of print.
Infection-induced inflammation from specific inborn errors of immunity to COVID-19
Cheng-Lung Ku[SUP] 1 2 [/SUP], I-Ting Chen[SUP] 3 [/SUP], Ming-Zong Lai[SUP] 3 [/SUP]
Affiliations
- PMID: 33971084
- DOI: 10.1111/febs.15961
Abstract
Inborn error of immunity (IEIs) are a group of genetically-defined disorders leading to defective immunity. Some IEIs have been linked to mutations of immune receptors or signaling molecules, resulting in defective signaling of respective cascades essential for combating specific pathogens. However, it remains incompletely understood why in selected IEIs, such as X-linked lymphoproliferative syndrome type-2 (XLP-2), hypo-immune response to specific pathogens results in persistent inflammation. Moreover, mechanisms underlying the generation of anti-cytokine autoantibodies are mostly unknown. Recently, IEIs have been associated with coronavirus disease 2019 (COVID-19), with a small proportion of patients that contract severe COVID-19 displaying loss-of-function mutations in genes associated with type I interferons (IFNs). Moreover, approximately 10% of patients with severe COVID-19 possess anti-type I IFN neutralizing autoantibodies. Apart from IEIs that impair immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV-2 encodes several proteins that suppress early type I IFN production. One primary consequence of the lack of type I IFNs during early SARS-CoV-2 infection is the increased inflammation associated with COVID-19. In XLP-2, resolution of inflammation rescued experimental subjects from infection-induced mortality. Recent studies also indicate that targeting inflammation could alleviate COVID-19. In this review, we discuss infection-induced inflammation in IEIs, using XLP-2 and COVID-19 as examples. We suggest that resolving inflammation may represent an effective therapeutic approach to these diseases.
Keywords: COVID-19; Inborn errors of immunity; SARS-CoV-2; XLP-2; anti-cytokine autoantibodies.