info:eu-repo/semantics/article
Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus
Fecha
2021-11Registro en:
Baroni Pietto, Maria Constanza; Lev, Paola Roxana; Glembotsky, Ana Claudia; Marín Oyarzún, Cecilia P.; Gomez, Graciela; et al.; Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus; Taylor & Francis Ltd; Platelets; 11-2021; 1-12
0953-7104
CONICET Digital
CONICET
Autor
Baroni Pietto, Maria Constanza
Lev, Paola Roxana
Glembotsky, Ana Claudia
Marín Oyarzún, Cecilia P.
Gomez, Graciela
Collado, Victoria
Pisoni, Cecilia
Gomez, Ramiro A.
Grodzielski, Matías
Gonzalez, Jacqueline
Mariño, Karina Valeria
Heller, Paula Graciela
Goette, Nora Paula
Marta, Rosana Fernanda
Resumen
Systemic lupus erythematosus (SLE) is an autoimmune condition developing thrombocytopenia in about 10?15% of cases, however, mechanisms leading to low platelet count were not deeply investigated in this illness. Here we studied possible causes of thrombocytopenia, including different mechanisms of platelet clearance and impairment in platelet production. Twenty-five SLE patients with and without thrombocytopenia were included. Platelet apoptosis, assessed by measurement of loss of mitochondrial membrane potential, active caspase 3 and phosphatidylserine exposure, was found to increase in thrombocytopenic patients. Plasma from 67% SLE patients (thrombocytopenic and non-thrombocytopenic) induced loss of sialic acid (Ricinus communis agglutinin I and/or Peanut agglutinin binding) from normal platelet glycoproteins. Concerning platelet production, SLE plasma increased megakaryopoiesis (evaluated using normal human cord blood CD34+ hematopoietic progenitors), but inhibited thrombopoiesis (proplatelet count). Anti-platelet autoantibody depletion from SLE plasma reverted this inhibition. Overall, abnormalities were more frequently observed in thrombocytopenic than non-thrombocytopenic SLE patients and in those with active disease (SLEDAI≥5). In conclusion, platelet clearance due to apoptosis and desialylation, and impaired platelet production mainly due to inhibition of thrombopoiesis, could be relevant mechanisms leading to thrombocytopenia in SLE. These findings could provide a rational basis for the choice of proper therapies to correct platelet counts in these patients.