Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection.
<h4>Background</h4>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 (EC...
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2013
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oai:doaj.org-article:d380dd0d4b7b473da9f684781e2554ed2021-11-18T08:54:06ZIncreased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection.1932-620310.1371/journal.pone.0074880https://doaj.org/article/d380dd0d4b7b473da9f684781e2554ed2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086391/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.Werner DammermannPim SchipperSebastian UllrichKatharina FraedrichJulian Schulze Zur WieschThorben FründtGisa TiegsAnsgar LohseStefan LüthPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74880 (2013) |
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Medicine R Science Q Werner Dammermann Pim Schipper Sebastian Ullrich Katharina Fraedrich Julian Schulze Zur Wiesch Thorben Fründt Gisa Tiegs Ansgar Lohse Stefan Lüth Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection. |
| description |
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| format |
article |
| author |
Werner Dammermann Pim Schipper Sebastian Ullrich Katharina Fraedrich Julian Schulze Zur Wiesch Thorben Fründt Gisa Tiegs Ansgar Lohse Stefan Lüth |
| author_facet |
Werner Dammermann Pim Schipper Sebastian Ullrich Katharina Fraedrich Julian Schulze Zur Wiesch Thorben Fründt Gisa Tiegs Ansgar Lohse Stefan Lüth |
| author_sort |
Werner Dammermann |
| title |
Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection. |
| title_short |
Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection. |
| title_full |
Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection. |
| title_fullStr |
Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection. |
| title_full_unstemmed |
Increased expression of complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4 infection. |
| title_sort |
increased expression of complement regulators cd55 and cd59 on peripheral blood cells in patients with eahec o104:h4 infection. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/d380dd0d4b7b473da9f684781e2554ed |
| work_keys_str_mv |
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