Autoimmunity Increases Susceptibility to and Mortality from Sepsis

Area of Science:

• Immunology
• Infectious Disease
• Neurology

Background:

• Sepsis can impact autoimmune disease development.
• The impact of pre-existing autoimmune conditions on sepsis susceptibility is poorly understood.
• Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system.

Purpose of the Study:

• To investigate the prevalence of sepsis in patients with multiple sclerosis (MS).
• To determine if autoimmune conditions, specifically experimental autoimmune encephalomyelitis (EAE) in mice, increase susceptibility to sepsis.
• To explore the mechanisms underlying increased sepsis mortality in autoimmune disease models.

Main Methods:

• Retrospective analysis of patient data from University of Iowa Hospital and Clinics.
• Utilized murine models of experimental autoimmune encephalomyelitis (EAE) and cecal ligation and puncture (CLP) to model MS and sepsis.
• Administered lipopolysaccharide (LPS) and Streptococcus pneumoniae to induce sepsis in EAE and control mice.

Main Results:

• MS patients exhibited a higher prevalence of sepsis compared to non-MS patients.
• EAE mice showed significantly increased mortality following sepsis induction compared to non-EAE controls.
• Sepsis in EAE mice was characterized by exacerbated cytokine storms.
• These findings were consistent across different sepsis models (CLP, LPS, S. pneumoniae).

Conclusions:

• Individuals with autoimmune diseases, such as MS, represent a high-risk population for sepsis.
• Pre-existing immune dysregulation in autoimmune conditions potentiates sepsis-induced mortality.
• Host immune status is a critical determinant of sepsis outcomes, emphasizing the need for identifying vulnerable patient groups.