Increased Expression of Complement Regulators CD55 and CD59 on Peripheral Blood Cells in Patients with EAHEC O104:H4 Infection

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

An outbreak of Shiga Toxin 2 (Stx-2) producing enterohemorrhagic and enteroaggregative E.coli (EAHEC) O104H4 infection in May 2011 caused enterocolitis and an unprecedented high 22% rate of hemolytic uremic syndrome (HUS). The monoclonal anti-C5 antibody Eculizumab (ECU) has been used experimentally in EAHEC patients with HUS but treatment efficacy is uncertain. ECU can effectively prevent hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) caused by a lack of complement-regulating CD55 and CD59 on blood cells. We hypothesized a low expression of CD55 and CD59, as seen in PNH, might correlate with HUS development in EAHEC patients.

Methods

76 EAHEC patients (34 only gastrointestinal symptoms [GI], 23: HUS, 19: HUS and neurological symptoms [HUS/N]) and 12 healthy controls (HC) were tested for the expression of CD55 and CD59 on erythrocytes and leukocytes retrospectively. Additionally, the effect of Stx-2 on CD55 and CD59 expression on erythrocytes and leukocytes was studied ex vivo.

Results

CD55 expression on erythrocytes was similar in all patient groups and HC while CD59 showed a significantly higher expression in HUS and HUS/N patients compared to HC and the GI group. CD55 and CD59 expression on leukocytes and their subsets was significantly higher in all patient groups compared to HC regardless of treatment type. However, CD59 expression on erythrocytes was significantly higher in HUS and HUS/N patients treated combined with plasma separation (PS) and ECU compared to HC. Adding Stx-2 ex vivo had no effect on CD55 and CD59 expression on leukocytes from HC or patients.

Conclusion

HUS evolved independently from CD55 and CD59 expression on peripheral blood cells in EAHEC O104:H4 infected patients. Our data do not support a role for CD55 and CD59 in HUS development during EAHEC O104:H4 infection and point to a different mechanism within the complement system for HUS development in EAHEC patients.

Related collections

Most cited references 27

Record: found
Abstract: not found
Article: not found

Eculizumab in severe Shiga-toxin-associated HUS.

Anne-Laure Lapeyraque, Michal Malina, Veronique Fremeaux-Bacchi … (2011)

0 comments Cited 106 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Genome sequence analyses of two isolates from the recent Escherichia coli outbreak in Germany reveal the emergence of a new pathotype: Entero-Aggregative-Haemorrhagic Escherichia coli (EAHEC)

Elzbieta Brzuszkiewicz, Andrea Thürmer, Jörg Schuldes … (2011)

The genome sequences of two Escherichia coli O104:H4 strains derived from two different patients of the 2011 German E. coli outbreak were determined. The two analyzed strains were designated E. coli GOS1 and GOS2 (German outbreak strain). Both isolates comprise one chromosome of approximately 5.31 Mbp and two putative plasmids. Comparisons of the 5,217 (GOS1) and 5,224 (GOS2) predicted protein-encoding genes with various E. coli strains, and a multilocus sequence typing analysis revealed that the isolates were most similar to the entero-aggregative E. coli (EAEC) strain 55989. In addition, one of the putative plasmids of the outbreak strain is similar to pAA-type plasmids of EAEC strains, which contain aggregative adhesion fimbrial operons. The second putative plasmid harbors genes for extended-spectrum β-lactamases. This type of plasmid is widely distributed in pathogenic E. coli strains. A significant difference of the E. coli GOS1 and GOS2 genomes to those of EAEC strains is the presence of a prophage encoding the Shiga toxin, which is characteristic for enterohemorrhagic E. coli (EHEC) strains. The unique combination of genomic features of the German outbreak strain, containing characteristics from pathotypes EAEC and EHEC, suggested that it represents a new pathotype Entero-Aggregative-Haemorrhagic E scherichia c oli (EAHEC). Electronic supplementary material The online version of this article (doi:10.1007/s00203-011-0725-6) contains supplementary material, which is available to authorized users.

0 comments Cited 88 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis.

Sara Gastoldi, Simona Buelli, Daniela Rottoli … (2011)

Shiga toxin (Stx)-producing E.coli O157:H7 has become a global threat to public health; it is a primary cause of diarrhea-associated hemolytic uremic syndrome (HUS), a disorder of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure with thrombi occluding renal microcirculation. In this study, we explored whether Stx triggers complement-dependent microvascular thrombosis in in vitro and in vivo experimental settings of HUS. Stx induced on human microvascular endothelial cell surface the expression of P-selectin, which bound and activated C3 via the alternative pathway, leading to thrombus formation under flow. In the search for mechanisms linking complement activation and thrombosis, we found that exuberant complement activation in response to Stx generated an increased amount of C3a that caused further endothelial P-selectin expression, thrombomodulin (TM) loss, and thrombus formation. In a murine model of HUS obtained by coinjection of Stx2 and LPS and characterized by thrombocytopenia and renal dysfunction, upregulation of glomerular endothelial P-selectin was associated with C3 and fibrin(ogen) deposits, platelet clumps, and reduced TM expression. Treatment with anti-P-selectin Ab limited glomerular C3 accumulation. Factor B-deficient mice after Stx2/LPS exhibited less thrombocytopenia and were protected against glomerular abnormalities and renal function impairment, indicating the involvement of complement activation via the alternative pathway in the glomerular thrombotic process in HUS mice. The functional role of C3a was documented by data showing that glomerular fibrin(ogen), platelet clumps, and TM loss were markedly decreased in HUS mice receiving C3aR antagonist. These results identify Stx-induced complement activation, via P-selectin, as a key mechanism of C3a-dependent microvascular thrombosis in diarrhea-associated HUS.

0 comments Cited 84 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Nades Palaniyar: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 23 September 2013

Volume: 8

Issue: 9

Electronic Location Identifier: e74880

Affiliations

[1 ]Department of Medicine, University Medical Center Eppendorf, Hamburg, Germany

[2 ]Department of Anatomy and Experimental Morphology, University Medical Center Eppendorf, Hamburg, Germany

[3 ]Institute of Experimental Immunology and Hepatology, University Medical Center Eppendorf, Hamburg, Germany

The Hospital for Sick Children and The University of Toronto, Canada

Author notes

* E-mail: s.lueth@ 123456uke.de

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: WD SU SL. Performed the experiments: WD PS. Analyzed the data: WD PS. Contributed reagents/materials/analysis tools: TF KF. Wrote the paper: WD GT JSZW AL SL.

Article

Publisher ID: PONE-D-13-22499

DOI: 10.1371/journal.pone.0074880

PMC ID: 3781141

PubMed ID: 24086391

SO-VID: 7803ef94-9247-46f3-a7fa-b65114657a83

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 30 May 2013

Date accepted : 7 August 2013

Page count

Pages: 10

Funding

This study is funded by the German Federal Ministry of Health and the Deutsche Forschungsgemeinschaft (DFG), grant # LU 1362/2-1 581069. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Increased Expression of Complement Regulators CD55 and CD59 on Peripheral Blood Cells in Patients with EAHEC O104:H4 Infection

Read this article at

Abstract

Background

Methods

Results

Conclusion

Related collections

PLOS: COVID-19 pandemic

Most cited references 27

Eculizumab in severe Shiga-toxin-associated HUS.

Genome sequence analyses of two isolates from the recent Escherichia coli outbreak in Germany reveal the emergence of a new pathotype: Entero-Aggregative-Haemorrhagic Escherichia coli (EAHEC)

Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 478

Cited by 3

Most referenced authors 888