Complement Activation and Thrombotic Microangiopathies
Background and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement a...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| Repositorio: | r-FISABIO. Repositorio Institucional de Producción Científica |
| OAI Identifier: | oai:fisabio.fundanetsuite.com:p4518 |
| Acceso en línea: | https://fisabio.portalinvestigacion.com/publicaciones/4518 |
| Access Level: | acceso abierto |
| Palabra clave: | humans pregnancy female atypical hemolytic uremic syndrome complement membrane HELLP syndrome complement C9 eculizumab complement pathway alternative pre-eclampsia hypertension malignant fibrin antibodies monoclonal humanized complement system proteins complement activation thrombotic microangiopathies recurrence fluorescent antibody technique endothelial cells |
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oai:fisabio.fundanetsuite.com:p4518 |
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Complement Activation and Thrombotic MicroangiopathiesPalomo MBlasco MMolina PLozano MPraga MTorramade-Moix SMartinez-Sanchez JCid JEscolar GCarreras EPaules CCrispi FQuintana LFPoch ERodas LGoma EMorelle JEspinosa MMorales EAvila ACabello VAriceta GChocron SManrique JBarros XMartin NHuerta AFraga-Rodriguez GMCao MMartin MRomera AMMoreso FManonelles AGratacos EPereira ACampistol JMDiaz-Ricart Mhumanspregnancyfemaleatypical hemolytic uremic syndromecomplement membraneHELLP syndromecomplement C9eculizumabcomplement pathwayalternativepre-eclampsiahypertensionmalignantfibrinantibodiesmonoclonalhumanizedcomplement system proteinscomplement activationthrombotic microangiopathiesrecurrencefluorescent antibody techniqueendothelial cellsBackground and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurementsComplement activation was assessed by exposing endothelial cells to sera or activated-patient plasma?citrated plasma mixed with a control sera pool (1:1)?to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.ResultsAcute phase atypical hemolytic uremic syndrome?activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6?9 months. Complement activation in those with malignant hypertension was at control levels.ConclusionsThe proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.American Society of Nephrology2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/4518Clinical journal of the American Society of NephrologyISSN: 1555905XISSNe: 15559041reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p45182026-06-11T12:45:17Z |
| dc.title.none.fl_str_mv |
Complement Activation and Thrombotic Microangiopathies |
| title |
Complement Activation and Thrombotic Microangiopathies |
| spellingShingle |
Complement Activation and Thrombotic Microangiopathies Palomo M humans pregnancy female atypical hemolytic uremic syndrome complement membrane HELLP syndrome complement C9 eculizumab complement pathway alternative pre-eclampsia hypertension malignant fibrin antibodies monoclonal humanized complement system proteins complement activation thrombotic microangiopathies recurrence fluorescent antibody technique endothelial cells |
| title_short |
Complement Activation and Thrombotic Microangiopathies |
| title_full |
Complement Activation and Thrombotic Microangiopathies |
| title_fullStr |
Complement Activation and Thrombotic Microangiopathies |
| title_full_unstemmed |
Complement Activation and Thrombotic Microangiopathies |
| title_sort |
Complement Activation and Thrombotic Microangiopathies |
| dc.creator.none.fl_str_mv |
Palomo M Blasco M Molina P Lozano M Praga M Torramade-Moix S Martinez-Sanchez J Cid J Escolar G Carreras E Paules C Crispi F Quintana LF Poch E Rodas L Goma E Morelle J Espinosa M Morales E Avila A Cabello V Ariceta G Chocron S Manrique J Barros X Martin N Huerta A Fraga-Rodriguez GM Cao M Martin M Romera AM Moreso F Manonelles A Gratacos E Pereira A Campistol JM Diaz-Ricart M |
| author |
Palomo M |
| author_facet |
Palomo M Blasco M Molina P Lozano M Praga M Torramade-Moix S Martinez-Sanchez J Cid J Escolar G Carreras E Paules C Crispi F Quintana LF Poch E Rodas L Goma E Morelle J Espinosa M Morales E Avila A Cabello V Ariceta G Chocron S Manrique J Barros X Martin N Huerta A Fraga-Rodriguez GM Cao M Martin M Romera AM Moreso F Manonelles A Gratacos E Pereira A Campistol JM Diaz-Ricart M |
| author_role |
author |
| author2 |
Blasco M Molina P Lozano M Praga M Torramade-Moix S Martinez-Sanchez J Cid J Escolar G Carreras E Paules C Crispi F Quintana LF Poch E Rodas L Goma E Morelle J Espinosa M Morales E Avila A Cabello V Ariceta G Chocron S Manrique J Barros X Martin N Huerta A Fraga-Rodriguez GM Cao M Martin M Romera AM Moreso F Manonelles A Gratacos E Pereira A Campistol JM Diaz-Ricart M |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
humans pregnancy female atypical hemolytic uremic syndrome complement membrane HELLP syndrome complement C9 eculizumab complement pathway alternative pre-eclampsia hypertension malignant fibrin antibodies monoclonal humanized complement system proteins complement activation thrombotic microangiopathies recurrence fluorescent antibody technique endothelial cells |
| topic |
humans pregnancy female atypical hemolytic uremic syndrome complement membrane HELLP syndrome complement C9 eculizumab complement pathway alternative pre-eclampsia hypertension malignant fibrin antibodies monoclonal humanized complement system proteins complement activation thrombotic microangiopathies recurrence fluorescent antibody technique endothelial cells |
| description |
Background and objectivesAtypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response.Design, setting, participants, & measurementsComplement activation was assessed by exposing endothelial cells to sera or activated-patient plasma?citrated plasma mixed with a control sera pool (1:1)?to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included.ResultsAcute phase atypical hemolytic uremic syndrome?activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6?9 months. Complement activation in those with malignant hypertension was at control levels.ConclusionsThe proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://fisabio.portalinvestigacion.com/publicaciones/4518 |
| url |
https://fisabio.portalinvestigacion.com/publicaciones/4518 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
American Society of Nephrology |
| publisher.none.fl_str_mv |
American Society of Nephrology |
| dc.source.none.fl_str_mv |
Clinical journal of the American Society of Nephrology ISSN: 1555905X ISSNe: 15559041 reponame:r-FISABIO. Repositorio Institucional de Producción Científica instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
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Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) |
| reponame_str |
r-FISABIO. Repositorio Institucional de Producción Científica |
| collection |
r-FISABIO. Repositorio Institucional de Producción Científica |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
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1869416392374091776 |
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15.811543 |