Complement Activation and Thrombotic Microangiopathies
Por:
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
Publicada:
6 dic 2019
Resumen:
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.
Filiaciones:
Palomo, M:
Univ Barcelona, Hosp Clin Barcelona, Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CDB,Hematopathol,Dept Pathol, Barcelona, Spain
Barcelona Endothelium Team, Barcelona, Spain
Blasco, M:
Univ Barcelona, Hosp Clin Barcelona, Dept Nephrol & Renal Transplantat, Barcelona, Spain
Grp Nephrourol Dis & Renal Transplantat IDIBAPS, Barcelona, Spain
Molina, P:
Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CDB,Hematopathol,Dept Pathol, Barcelona, Spain
Lozano, M:
Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, ICMHO,Dept Hemotherapy & Hemostasis,Apheresis Uni, Barcelona, Spain
Praga, M:
Hosp Univ 12 Octubre, Dept Nephrol, Madrid, Spain
Res Inst I 12, Madrid, Spain
Univ Complutense, Dept Med, Madrid, Spain
Torramade-Moix, S:
Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CDB,Hematopathol,Dept Pathol, Barcelona, Spain
Martinez-Sanchez, J:
Univ Barcelona, Hosp Clin Barcelona, Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CDB,Hematopathol,Dept Pathol, Barcelona, Spain
Barcelona Endothelium Team, Barcelona, Spain
Cid, J:
Univ Barcelona, Hosp Clin Barcelona, IDIBAPS, ICMHO,Dept Hemotherapy & Hemostasis,Apheresis Uni, Barcelona, Spain
Escolar, G:
Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CDB,Hematopathol,Dept Pathol, Barcelona, Spain
Carreras, E:
Univ Barcelona, Hosp Clin Barcelona, Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Barcelona Endothelium Team, Barcelona, Spain
Paules, C:
Univ Barcelona, IDIBAPS, Hosp Clin Barcelona,Fetal I D Fetal Med Res Ctr, ICGON,BCNatal Barcelona Ctr Maternal Fetal & Neon, Barcelona, Spain
Univ Barcelona, IDIBAPS, ICGON, Hosp St Joan de Deu, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Barcelona, Spain
Crispi, F:
Univ Barcelona, IDIBAPS, Hosp Clin Barcelona,Fetal I D Fetal Med Res Ctr, ICGON,BCNatal Barcelona Ctr Maternal Fetal & Neon, Barcelona, Spain
Univ Barcelona, IDIBAPS, ICGON, Hosp St Joan de Deu, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Barcelona, Spain
Quintana, LF:
Univ Barcelona, Hosp Clin Barcelona, Dept Nephrol & Renal Transplantat, Barcelona, Spain
Grp Nephrourol Dis & Renal Transplantat IDIBAPS, Barcelona, Spain
Poch, E:
Univ Barcelona, Hosp Clin Barcelona, Dept Nephrol & Renal Transplantat, Barcelona, Spain
Grp Nephrourol Dis & Renal Transplantat IDIBAPS, Barcelona, Spain
Rodas, L:
Univ Barcelona, Hosp Clin Barcelona, Dept Nephrol & Renal Transplantat, Barcelona, Spain
Goma, E:
Univ Barcelona, Hosp Clin Barcelona, Dept Nephrol & Renal Transplantat, Barcelona, Spain
Morelle, J:
Catholic Univ Louvain, Inst Rech Expt & Clin, Iniques Univ St Luc, Div Nephrol, Brussels, Belgium
Espinosa, M:
Hosp Univ Reina Sofia, Dept Nephrol, Cordoba, Spain
Inst Maimonides Invest Biol Cordoba IMIBIC, Cordoba, Spain
Morales, E:
Hosp Univ 12 Octubre, Dept Nephrol, Madrid, Spain
Res Inst I 12, Madrid, Spain
Avila, A:
Hosp Univ Dr Peset, Dept Nephrol & Renal Transplantat, Valencia, Spain
Cabello, V:
Hosp Virgen del Rocio, Dept Nephrol, Seville, Spain
Ariceta, G:
Univ Autonoma Barcelona, Hosp Materno Infantil, Dept Pediat Nephrol, Barcelona, Spain
Chocron, S:
Univ Autonoma Barcelona, Hosp Materno Infantil, Dept Pediat Nephrol, Barcelona, Spain
Manrique, J:
Complejo Hosp Navarra, Dept Nephrol, Pamplona, Spain
Barros, X:
Hosp Univ Josep Trueta, Dept Nephrol, Girona, Spain
Martin, N:
Hosp Univ Josep Trueta, Dept Nephrol, Girona, Spain
Huerta, A:
Hosp Puerta de Hierro Majadahonda, Dept Nephrol, Madrid, Spain
Fraga-Rodriguez, GM:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Pediat Nephrol, Barcelona, Spain
Cao, M:
Complejo Hosp Univ A Coruna, Dept Nephrol, Coruna, Spain
Martin, M:
Hosp Arnau Vilanova, Dept Nephrol, Lleida, Spain
Romera, AM:
Hosp Gen Univ, Dept Nephrol, Ciudad Real, Spain
Moreso, F:
Univ Autonoma Barcelona, Hosp Univ Vall dHebron, Dept Nephrol, Barcelona, Spain
Manonelles, A:
Univ Barcelona, Hosp Bellvitge, Dept Nephrol, Kidney Transplant Unit, Barcelona, Spain
Gratacos, E:
Univ Barcelona, IDIBAPS, Hosp Clin Barcelona,Fetal I D Fetal Med Res Ctr, ICGON,BCNatal Barcelona Ctr Maternal Fetal & Neon, Barcelona, Spain
Univ Barcelona, IDIBAPS, ICGON, Hosp St Joan de Deu, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Barcelona, Spain
Pereira, A:
CDB, Barcelona, Spain
Campistol, JM:
Univ Barcelona, Hosp Clin Barcelona, Dept Nephrol & Renal Transplantat, Barcelona, Spain
Diaz-Ricart, M:
Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, CDB,Hematopathol,Dept Pathol, Barcelona, Spain
Barcelona Endothelium Team, Barcelona, Spain
Green Published, Bronze
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