Human serum amyloid P component protects against Escherichia coli O157:H7 shiga toxin 2 in vivo: Therapeutic implications for hemolytic-uremic syndrome

Glen D. Armstrong; George L. Mulvey; Paola Marcato; Thomas P. Griener; Melvyn C. Kahan; Glenys A. Tennent; Caroline A. Sabin; Henrik Chart; Mark B. Pepys

doi:10.1086/501472

Human serum amyloid P component protects against Escherichia coli O157:H7 shiga toxin 2 in vivo: Therapeutic implications for hemolytic-uremic syndrome

Glen D. Armstrong^*
, George L. Mulvey
, Paola Marcato
, Thomas P. Griener
, Melvyn C. Kahan
, Glenys A. Tennent
, Caroline A. Sabin
, Henrik Chart
, Mark B. Pepys

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

43 Citations (Scopus)

Abstract

Shiga toxin (Stx) 2 causes hemolytic-uremic syndrome (HUS), an intractable and often fatal complication of enterohemorrhagic Escherichia coli O157:H7 infection. Here, we show that serum amyloid P component (SAP), a normal human plasma protein, specifically protects mice against the lethal toxicity of Stx2, both when injected into wild-type mice and when expressed transgenically; in the presence of human SAP, there was greatly reduced in vivo localization of Stx2 to the kidneys, suggesting a possible mechanism of protection. In humans, circulating SAP concentrations did not differ between patients with suspected enterohemorrhagic E. coli infection with antibodies to E. coli O157:H7 lipopolysaccharide and those without antibodies or between patients with HUS and those without it. However, the potent protection conferred by human SAP in the mouse model suggests that infusion of supplemental SAP may be a useful novel therapeutic approach to the treatment of this devastating condition.

Original language	English
Pages (from-to)	1120-1124
Number of pages	5
Journal	Journal of Infectious Diseases
Volume	193
Issue number	8
DOIs	https://doi.org/10.1086/501472
Publication status	Published - 15 Apr 2006

Bibliographical note

Funding Information:
Financial support: Canadian Institutes for Health Research (operating grant MWS 56081 to G.D.A. and doctoral scholarship to P.M.); Canadian Bacterial Diseases Network (operating grant VP 17 to G.D.A.); Alberta Heritage Foundation for Medical Research (doctoral scholarship to P.M.); UK Medical Research Council Programme (grant G97900510 to M.B.P.).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1086/501472

Cite this

Armstrong, G. D., Mulvey, G. L., Marcato, P., Griener, T. P., Kahan, M. C., Tennent, G. A., Sabin, C. A., Chart, H., & Pepys, M. B. (2006). Human serum amyloid P component protects against Escherichia coli O157:H7 shiga toxin 2 in vivo: Therapeutic implications for hemolytic-uremic syndrome. Journal of Infectious Diseases, 193(8), 1120-1124. https://doi.org/10.1086/501472

@article{8344e8aa67d94c05850cb16449b3a472,

title = "Human serum amyloid P component protects against Escherichia coli O157:H7 shiga toxin 2 in vivo: Therapeutic implications for hemolytic-uremic syndrome",

abstract = "Shiga toxin (Stx) 2 causes hemolytic-uremic syndrome (HUS), an intractable and often fatal complication of enterohemorrhagic Escherichia coli O157:H7 infection. Here, we show that serum amyloid P component (SAP), a normal human plasma protein, specifically protects mice against the lethal toxicity of Stx2, both when injected into wild-type mice and when expressed transgenically; in the presence of human SAP, there was greatly reduced in vivo localization of Stx2 to the kidneys, suggesting a possible mechanism of protection. In humans, circulating SAP concentrations did not differ between patients with suspected enterohemorrhagic E. coli infection with antibodies to E. coli O157:H7 lipopolysaccharide and those without antibodies or between patients with HUS and those without it. However, the potent protection conferred by human SAP in the mouse model suggests that infusion of supplemental SAP may be a useful novel therapeutic approach to the treatment of this devastating condition.",

author = "Armstrong, \{Glen D.\} and Mulvey, \{George L.\} and Paola Marcato and Griener, \{Thomas P.\} and Kahan, \{Melvyn C.\} and Tennent, \{Glenys A.\} and Sabin, \{Caroline A.\} and Henrik Chart and Pepys, \{Mark B.\}",

note = "Funding Information: Financial support: Canadian Institutes for Health Research (operating grant MWS 56081 to G.D.A. and doctoral scholarship to P.M.); Canadian Bacterial Diseases Network (operating grant VP 17 to G.D.A.); Alberta Heritage Foundation for Medical Research (doctoral scholarship to P.M.); UK Medical Research Council Programme (grant G97900510 to M.B.P.).",

year = "2006",

month = apr,

day = "15",

doi = "10.1086/501472",

language = "English",

volume = "193",

pages = "1120--1124",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "8",

}

TY - JOUR

T1 - Human serum amyloid P component protects against Escherichia coli O157:H7 shiga toxin 2 in vivo

T2 - Therapeutic implications for hemolytic-uremic syndrome

AU - Armstrong, Glen D.

AU - Mulvey, George L.

AU - Marcato, Paola

AU - Griener, Thomas P.

AU - Kahan, Melvyn C.

AU - Tennent, Glenys A.

AU - Sabin, Caroline A.

AU - Chart, Henrik

AU - Pepys, Mark B.

N1 - Funding Information: Financial support: Canadian Institutes for Health Research (operating grant MWS 56081 to G.D.A. and doctoral scholarship to P.M.); Canadian Bacterial Diseases Network (operating grant VP 17 to G.D.A.); Alberta Heritage Foundation for Medical Research (doctoral scholarship to P.M.); UK Medical Research Council Programme (grant G97900510 to M.B.P.).

PY - 2006/4/15

Y1 - 2006/4/15

N2 - Shiga toxin (Stx) 2 causes hemolytic-uremic syndrome (HUS), an intractable and often fatal complication of enterohemorrhagic Escherichia coli O157:H7 infection. Here, we show that serum amyloid P component (SAP), a normal human plasma protein, specifically protects mice against the lethal toxicity of Stx2, both when injected into wild-type mice and when expressed transgenically; in the presence of human SAP, there was greatly reduced in vivo localization of Stx2 to the kidneys, suggesting a possible mechanism of protection. In humans, circulating SAP concentrations did not differ between patients with suspected enterohemorrhagic E. coli infection with antibodies to E. coli O157:H7 lipopolysaccharide and those without antibodies or between patients with HUS and those without it. However, the potent protection conferred by human SAP in the mouse model suggests that infusion of supplemental SAP may be a useful novel therapeutic approach to the treatment of this devastating condition.

AB - Shiga toxin (Stx) 2 causes hemolytic-uremic syndrome (HUS), an intractable and often fatal complication of enterohemorrhagic Escherichia coli O157:H7 infection. Here, we show that serum amyloid P component (SAP), a normal human plasma protein, specifically protects mice against the lethal toxicity of Stx2, both when injected into wild-type mice and when expressed transgenically; in the presence of human SAP, there was greatly reduced in vivo localization of Stx2 to the kidneys, suggesting a possible mechanism of protection. In humans, circulating SAP concentrations did not differ between patients with suspected enterohemorrhagic E. coli infection with antibodies to E. coli O157:H7 lipopolysaccharide and those without antibodies or between patients with HUS and those without it. However, the potent protection conferred by human SAP in the mouse model suggests that infusion of supplemental SAP may be a useful novel therapeutic approach to the treatment of this devastating condition.

UR - https://www.scopus.com/pages/publications/33645762261

U2 - 10.1086/501472

DO - 10.1086/501472

M3 - Article

C2 - 16544252

AN - SCOPUS:33645762261

SN - 0022-1899

VL - 193

SP - 1120

EP - 1124

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 8

ER -

Human serum amyloid P component protects against Escherichia coli O157:H7 shiga toxin 2 in vivo: Therapeutic implications for hemolytic-uremic syndrome

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this