Role of Shiga toxin 2 (Stx2)-binding protein, human serum amyloid P component (HuSAP), in Shiga toxin-producing Escherichia coli infections: assumption from in vitro and in vivo study using HuSAP and anti-Stx2 humanized monoclonal antibody TMA-15.
Shiga toxin 2 (Stx2) is a major pathogenic factor in Shiga toxin-producing Escherichia coli (STEC) infections. Some factor that neutralizes Stx2 in vitro had been shown to be specifically present in human serum and we recently identified it as human serum amyloid P component (HuSAP). Here, we report the role of HuSAP in STEC infections. HuSAP could not rescue Stx2-challenged mice from death, and it instead reduced the efficacy of the Stx2-neutralizing humanized monoclonal antibody TMA-15 when a lower dose of TMA-15 was injected to the mice. By contrast, the efficacy of TMA-15 at a higher dose was uninfluenced by the presence of HuSAP. These findings suggest that HuSAP acts as a carrier protein of Stx2 rather than as a Stx2-neutralizing factor in the human circulation and that passive immune therapy with Stx2-neutralizing antibodies such as TMA-15 is useful to prevent severe complications associated with STEC infections even in the presence of HuSAP.
Kimura
Tsuyoshi
T
Teijin Institute for Bio-medical Research, Teijin Ltd., 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan. t.kimura@teijin.co.jp
Tani
Shinobu
S
Motoki
Masamichi
M
Matsumoto
Yoh-ichi
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000502:physiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000209:etiology* / Q000382:microbiology / Q000628:therapy; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D000683:Serum Amyloid P-Component / Q000502:physiology*; D022641:Shiga Toxin 2 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism / Q000633:toxicity
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D002352:Carrier Proteins; D000683:Serum Amyloid P-Component; D022641:Shiga Toxin 2; C437063:urtoxazumab