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Key Event Title
Increase, Increased susceptibility to infection
Key Event Components
Key Event Overview
AOPs Including This Key Event
|All life stages||High|
Key Event Description
Severe combined immunodeficiencies (SCIDs) comprise a group of rare, monogenic diseases that are characterized by an early onset and a profound block in the development of T lymphocytes. Given that adaptive immunity is abrogated, patients with SCID are prone to recurrent infections caused by both non-opportunistic and opportunistic pathogens, leading to early death unless immunity can be restored （reviewed by Fischer et al. (Fischer et al., 2015)）. Human immunodeficiency virus (HIV) is a retrovirus known to attack the CD4+ T lymphocytes. In individuals with chronic HIV infection not on treatment with antiretroviral agents, as the CD4+ count drops they are vulnerable to a multitude of infections which rarely occur in an immunocompetent host, hence the term opportunistic infections (Justiz Vaillant and Naik, 2021). Various immunosuppressive agents such as corticosteroids, antimetabolites, calcineurin inhibitors, glucocorticoids, antithymocyte globulin, antibodies against IL-2RA or CD28, which all suppress T cell function, increase the incidence of opportunistic infection (reviewed by Tasdogan et al. (Tasdogan et al., 2019).
How It Is Measured or Detected
By comparison of the incidence of infection between individuals exposed to stressors and non-exposed individuals.
Domain of Applicability
The increased susceptibility to infection caused by IL-1RA or anti-IL-1 antibody has been reported in both humans and mice (De Benedetti et al., 2018; Fleischmann et al., 2003).
Evidence for Perturbation by Stressor
Regulatory Significance of the Adverse Outcome
Increased susceptibility to infection is the significant adverse outcome of drugs and chemicals present in the environment. Therefore, drugs or chemicals that have an effect that can cause immunosuppression must be under regulatory scrutiny.
De Benedetti, F., Gattorno, M., Anton, J., et al. (2018), Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. N Engl J Med 378: 1908-1919, 10.1056/NEJMoa1706314
Fischer, A., Notarangelo, L.D., Neven, B., et al. (2015), Severe combined immunodeficiencies and related disorders. Nat Rev Dis Primers 1: 15061, 10.1038/nrdp.2015.61
Fleischmann, R.M., Schechtman, J., Bennett, R., et al. (2003), Anakinra, a recombinant human interleukin-1 receptor antagonist (r-metHuIL-1ra), in patients with rheumatoid arthritis: A large, international, multicenter, placebo-controlled trial. Arthritis Rheum 48: 927-934, 10.1002/art.10870
Justiz Vaillant, A.A., Naik, R. 2021. HIV-1 Associated Opportunistic Infections, StatPearls. StatPearls Publishing
Copyright © 2021, StatPearls Publishing LLC., Treasure Island (FL).
Tasdogan, B.E., Ma, M., Simsek, C., et al. (2019), Update on Immunosuppression in Liver Transplantation. Euroasian J Hepatogastroenterol 9: 96-101, 10.5005/jp-journals-10018-1301