Do reduced numbers of plasmacytoid dendritic cells contribute to the aggressive clinical course of COVID‐19 in chronic lymphocytic leukaemia?

Smith, C. I. Edvard; Zain, Rula; Österborg, Anders; Palma, Marzia; Buggert, Marcus; Bergman, Peter; Bryceson, Yenan T.

doi:10.1111/sji.13153

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…Patients with IRAK4 or MyD88 deficiency were subsequently found to be at very high risk of life-threatening COVID-19 pneumonia ( 65 ). These findings are consistent with the demonstration that plasmacytoid dendritic cells (pDCs) are dependent on IRAK4 and TLR7 for SARS-CoV-2 sensing and type I IFN production ( 64 , 66 ) and with the observation that patients with chronic lymphocytic leukemia have diminished counts of pDCs and are prone to hypoxemic COVID-19 pneumonia ( 67 ).…”

Section: Inborn Errors Of Type I Ifn Immunity To Virusessupporting

confidence: 88%

Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Casanova¹,

Anderson²

2023

Journal of Clinical Investigation

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Since 2003, rare inborn errors of human type I IFN immunity have been discovered, each underlying a few severe viral illnesses. Autoantibodies neutralizing type I IFNs due to rare inborn errors of autoimmune regulator (AIRE)–driven T cell tolerance were discovered in 2006, but not initially linked to any viral disease. These two lines of clinical investigation converged in 2020, with the discovery that inherited and/or autoimmune deficiencies of type I IFN immunity accounted for approximately 15%–20% of cases of critical COVID-19 pneumonia in unvaccinated individuals. Thus, insufficient type I IFN immunity at the onset of SARS-CoV-2 infection may be a general determinant of life-threatening COVID-19. These findings illustrate the unpredictable, but considerable, contribution of the study of rare human genetic diseases to basic biology and public health.

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Section: Inborn Errors Of Type I Ifn Immunity To Virusessupporting

confidence: 88%

Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Casanova¹,

Anderson²

2023

Journal of Clinical Investigation

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“…Further, CLL is associated with hypogammaglobulinemia, T cell abnormalities, impaired complement, and phagocytic system[ 9 , 10 ]. Specifically, a lack of plasmacytoid dendritic cells, key producers of type I interferon, was proposed as an underlying mechanism for the aggressive clinical course of COVID-19 in CLL [ 21 ]. These substantial immune defects result in severe disruptions in defense mechanisms against infections.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 in patients with chronic lymphocytic leukemia: a multicenter analysis by the Czech CLL study group

et al. 2023

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Patients with chronic lymphocytic leukemia (CLL) have a high risk of poor outcomes related to coronavirus disease 2019 (COVID-19). This multicenter cohort study evaluated the impact of COVID-19 infection on the population of CLL patients in the Czech Republic. Between March 2020 and May 2021, 341 patients (237 males) with CLL and COVID-19 disease were identified. The median age was 69 years (range 38–91). Out of the 214 (63%) patients with the history of therapy for CLL, 97 (45%) were receiving CLL-directed treatment at diagnosis of COVID-19: 29% Bruton tyrosine kinase inhibitor (BTKi), 16% chemoimmunotherapy (CIT), 11% Bcl-2 inhibitor, and 4% phosphoinositide 3-kinase inhibitor. Regarding the severity of COVID-19, 60% pts required admission to the hospital, 21% pts were admitted to the intensive care unit (ICU), and 12% received invasive mechanical ventilation. The overall case fatality rate was 28%. Major comorbidities, age over 72, male gender, CLL treatment in history, CLL-directed treatment at COVID-19 diagnosis were associated with increased risk of death. Of note, concurrent therapy with BTKi compared to CIT was not associated with better outcome of COVID-19.

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“…sequenced the genome or exome of 659 patients with COVID-19 to test 118 rare nonsynonymous variants of 13 human loci that underlie life-threatening influenza pneumonia. Autosomal-recessive and autosomal-dominant deficiencies of IRF7 are involved in the TLR3- and IRF7-dependent induction and amplification of IFN-I ( 138 ), and TLR7 together with IRF7 combat COVID-19 by the large amounts of IFN-I produced by pDCs ( 139 ). However, Povysil G et al.…”

Section: The Function Of Irf7mentioning

confidence: 99%

IRF7: role and regulation in immunity and autoimmunity

Huang

Wang

et al. 2023

Front. Immunol.

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Interferon regulatory factor (IRF) 7 was originally identified as master transcriptional factor that produced IFN-I and regulated innate immune response, subsequent studies have revealed that IRF7 performs a multifaceted and versatile functions in multiple biological processes. In this review, we provide a comprehensive overview on the current knowledge of the role of IRF7 in immunity and autoimmunity. We focus on the latest regulatory mechanisms of IRF7 in IFN-I, including signaling pathways, transcription, translation, and post-translational levels, the dimerization and nuclear translocation, and the role of IRF7 in IFN-III and COVID-19. In addition to antiviral immunity, we also discuss the role and mechanism of IRF7 in autoimmunity, and the further research will expand our understanding of IRF7.

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Do reduced numbers of plasmacytoid dendritic cells contribute to the aggressive clinical course of COVID‐19 in chronic lymphocytic leukaemia?

Cited by 7 publications

References 45 publications

Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs

COVID-19 in patients with chronic lymphocytic leukemia: a multicenter analysis by the Czech CLL study group

IRF7: role and regulation in immunity and autoimmunity

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