Llama heavy-chain antibody fragments efficiently remove toxic shock syndrome toxin 1 from plasma in vitro but not in experimental porcine septic shock.

Abstract

Staphylococcus aureus produces the superantigen toxic shock syndrome toxin 1 (TSST-1). When the bacterium invades the human circulation, this toxin can induce life-threatening gram-positive sepsis. Current sepsis treatment does not remove bacterial toxins. Variable domains of llama heavy-chain antibodies (VHH) against toxic shock syndrome toxin 1 ([alpha]-TSST-1 VHH) were previously found to be effective in vitro. We hypothesized that removing TSST-1 with [alpha]-TSST-1 VHH hemofiltration filters would ameliorate experimental sepsis in pigs. After assessing in vitro whether timely removing TSST-1 interrupted TSST-1-induced mononuclear cell TNF-[alpha] production, VHH-coated filters were applied in a porcine sepsis model. Clinical course, survival, plasma interferon [gamma], and TSST-1 levels were similar with and without VHH-coated filters as were TSST-1 concentrations before and after the VHH filter. Plasma TSST-1 levels were much lower than anticipated from the distribution of the amount of infused TSST-1, suggesting compartmentalization to space or adhesion to surface not accessible to hemofiltration or pheresis techniques. Removing TSST-1 from plasma was feasible in vitro. However, the [alpha]-TSST-1 VHH adsorption filter-based technique was ineffective in vivo, indicating that improvement of VHH-based hemofiltration is required. Sequestration likely prevented the adequate removal of TSST-1. The latter warrants further investigation of TSST-1 distribution and clearance in vivo.

• Authors: Walter J Brummelhuis, Jaap A Joles, Jord C Stam, Hendrik Adams, Roel Goldschmeding, Frank J Detmers, Mohamed El Khattabi, Bram T Maassen, C Theo Verrips, Branko Braam
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 34 Issue 2 Pg. 125-32 (Aug 2010) ISSN: 1540-0514 [Electronic] United States
• PMID: 20016410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Toxins
• Enterotoxins
• Immunoglobulin Heavy Chains
• Peptide Fragments
• Superantigens
• enterotoxin F, Staphylococcal

Topics

• Animals
• Bacterial Toxins
• Camelids, New World (immunology)
• Cells, Cultured
• Enterotoxins
• Female
• Hemofiltration (methods)
• Humans
• Immunoglobulin Heavy Chains (therapeutic use)
• Leukocytes, Mononuclear (metabolism)
• Peptide Fragments (therapeutic use)
• Shock, Septic (immunology, prevention & control)
• Superantigens
• Sus scrofa