Portal de investigación
Complement Activation and Thrombotic Microangiopathies
Fecha de publicación:
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Autores de FISABIO
Autores ajenos a FISABIO
- 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
- 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
Grupos de Investigación
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 1555-905X, 1555-9041
- Tipo:
- Article
- Páginas:
- 1719-1732
- DOI:
- 10.2215/CJN.05830519
- PubMed:
- 31694864
Clinical journal of the American Society of Nephrology American Society of Nephrology
Citas Recibidas en Web of Science: 68
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Filiaciones
Keywords
- 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