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Autoimmunity Increases Susceptibility to and Mortality from Sepsis
Journal article   Open access   Peer reviewed

Autoimmunity Increases Susceptibility to and Mortality from Sepsis

Isaac J Jensen, Samantha N Jensen, Patrick W McGonagill, Thomas S Griffith, Ashutosh K Mangalam and Vladimir P Badovinac
ImmunoHorizons, Vol.5(10), pp.844-854
10/01/2021
DOI: 10.4049/immunohorizons.2100070
PMCID: PMC9036850
PMID: 34702761
url
https://doi.org/10.4049/immunohorizons.2100070View
Published (Version of record) Open Access

Abstract

We recently demonstrated how sepsis influences the subsequent development of experimental autoimmune encephalomyelitis (EAE) presented a conceptual advance in understanding the postsepsis chronic immunoparalysis state. However, the reverse scenario (autoimmunity prior to sepsis) defines a high-risk patient population whose susceptibility to sepsis remains poorly defined. In this study, we present a retrospective analysis of University of Iowa Hospital and Clinics patients demonstrating increased sepsis prevalence among multiple sclerosis (MS), relative to non-MS, patients. To interrogate how autoimmune disease influences host susceptibility to sepsis, well-established murine models of MS and sepsis and EAE and cecal ligation and puncture, respectively, were used. EAE, relative to non-EAE, mice were highly susceptible to sepsis-induced mortality with elevated cytokine storms. These results were further recapitulated in LPS and Streptococcus pneumoniae sepsis models. This work highlights both the relevance of identifying highly susceptible patient populations and expands the growing body of literature that host immune status at the time of septic insult is a potent mortality determinant.

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