RT Journal Article
T1 Complement Activation and Thrombotic Microangiopathies.
A1 Palomo, Marta
A1 Blasco, Miquel
A1 Molina, Patricia
A1 Lozano, Miquel
A1 Praga, Manuel
A1 Torramade-Moix, Sergi
A1 Martinez-Sanchez, Julia
A1 Cid, Joan
A1 Escolar, Gines
A1 Carreras, Enric
A1 Paules, Cristina
A1 Crispi, Fatima
A1 Quintana, Luis F
A1 Poch, Esteban
A1 Rodas, Lida
A1 Goma, Emma
A1 Morelle, Johann
A1 Espinosa, Mario
A1 Morales, Enrique
A1 Avila, Ana
A1 Cabello, Virginia
A1 Ariceta, Gema
A1 Chocron, Sara
A1 Manrique, Joaquin
A1 Barros, Xoana
A1 Martin, Nadia
A1 Huerta, Ana
A1 Fraga-Rodriguez, Gloria M
A1 Cao, Mercedes
A1 Martin, Marisa
A1 Romera, Ana Maria
A1 Moreso, Francesc
A1 Manonelles, Anna
A1 Gratacos, Eduard
A1 Pereira, Arturo
A1 Campistol, Josep M
A1 Diaz-Ricart, Maribel
K1 HELLP syndrome
K1 alternative
K1 antibodies
K1 atypical hemolytic uremic syndrome
K1 complement C9
K1 complement activation
K1 complement membrane
K1 complement pathway
K1 complement system proteins
K1 eculizumab
K1 endothelial cells
K1 female
K1 fibrin
K1 fluorescent antibody technique
K1 humanized
K1 humans
K1 hypertension
K1 malignant
K1 monoclonal
K1 pre-eclampsia
K1 pregnancy
K1 recurrence
K1 thrombotic microangiopathies
AB Atypical 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. Complement 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. Acute 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. The 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.
YR 2019
FD 2019-11-06
LK http://hdl.handle.net/10668/14648
UL http://hdl.handle.net/10668/14648
LA en
DS RISalud
RD Apr 12, 2025