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Human polyspecific immunoglobulin attenuates group A streptococcal virulence factor activity and reduces disease

A Tarnutzer1, F Andreoni1, N Keller1

  • 1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases
|July 21, 2018
PubMed
Abstract

Insights

Intravenous immunoglobulin (IVIG) effectively reduced disease severity in a mouse model of necrotizing fasciitis (NF) by inhibiting key virulence factors. These findings suggest IVIG may benefit patients with invasive Streptococcus pyogenes infections.

Area of Science:

  • Infectious Diseases
  • Immunology
  • Microbiology

Background:

  • Streptococcus pyogenes causes severe invasive infections like necrotizing fasciitis (NF).
  • Current NF treatment involves antibiotics and surgery, with adjunctive intravenous immunoglobulin (IVIG) therapy explored for streptococcal toxic shock syndrome.
  • The efficacy of IVIG in invasive infections remains unclear due to limited prospective studies.

Purpose of the Study:

  • To evaluate the impact of IVIG on Streptococcus pyogenes virulence factor activity.
  • To assess IVIG's therapeutic potential in a murine model of NF.
  • To investigate IVIG's effect on virulence factors in vitro, ex vivo in patients, and in vivo.

Main Methods:

  • Investigated IVIG's effect on streptolysin O (SLO), streptodornase 1 (Sda1), S. pyogenes cell envelope protease, and streptococcal pyrogenic exotoxin B in vitro and in patient sera.
  • Assessed clinical outcomes in a murine NF model following IVIG administration.
  • Measured changes in virulence factor activity and antibody titers in patient sera post-IVIG treatment.

Main Results:

  • In vitro, IVIG inhibited multiple streptococcal virulence factors.
  • IVIG treatment significantly reduced skin lesion size and SLO activity in a murine NF model.
  • Patient sera showed increased specific antibodies against SLO and Sda1 after IVIG, reducing their activity.

Conclusions:

  • IVIG demonstrated a clear reduction in disease severity in a mouse model of NF.
  • IVIG effectively inhibited streptococcal virulence factors in both mouse and human samples.
  • Findings suggest IVIG could be a beneficial adjunctive therapy for invasive Streptococcus pyogenes infections, including NF.
Keywords:
Adjunctive treatmentGroup A StreptococcusNecrotizing fasciitisPolyspecific human intravenous immunoglobulinStreptococcus pyogenesVirulence factor activity

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