Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus
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 p...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-07-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2021.1988547 |
| _version_ | 1797684138368565248 |
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| author | M. Constanza Baroni Pietto Paola R. Lev Ana C. Glembotsky Cecilia P. Marín Oyarzún Graciela Gomez Victoria Collado Cecilia Pisoni Ramiro A. Gomez Matías Grodzielski Jacqueline Gonzalez Karina V. Mariño Paula G. Heller Nora P. Goette Rosana F. Marta |
| author_facet | M. Constanza Baroni Pietto Paola R. Lev Ana C. Glembotsky Cecilia P. Marín Oyarzún Graciela Gomez Victoria Collado Cecilia Pisoni Ramiro A. Gomez Matías Grodzielski Jacqueline Gonzalez Karina V. Mariño Paula G. Heller Nora P. Goette Rosana F. Marta |
| author_sort | M. Constanza Baroni Pietto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:25:10Z |
| format | Article |
| id | doaj.art-6b513b6ff98045f69f1dba0a75e76380 |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:25:10Z |
| publishDate | 2022-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-6b513b6ff98045f69f1dba0a75e763802023-09-15T10:38:10ZengTaylor & Francis GroupPlatelets0953-71041369-16352022-07-0133574375410.1080/09537104.2021.19885471988547Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosusM. Constanza Baroni Pietto0Paola R. Lev1Ana C. Glembotsky2Cecilia P. Marín Oyarzún3Graciela Gomez4Victoria Collado5Cecilia Pisoni6Ramiro A. Gomez7Matías Grodzielski8Jacqueline Gonzalez9Karina V. Mariño10Paula G. Heller11Nora P. Goette12Rosana F. Marta13Conicet – Universidad De Buenos Aires. Unidad Ejecutora Idim-conicet (Ue Idim-conicet)Conicet – Universidad De Buenos Aires. Unidad Ejecutora Idim-conicet (Ue Idim-conicet)Conicet – Universidad De Buenos Aires. Unidad Ejecutora Idim-conicet (Ue Idim-conicet)Conicet – Universidad De Buenos Aires. Unidad Ejecutora Idim-conicet (Ue Idim-conicet)Universidad De Buenos Aires. Instituto De Investigaciones Médicas Alfredo LanariUniversidad De Buenos Aires. Instituto De Investigaciones Médicas Alfredo LanariCentro De Educación Médica E Investigación Clínica “Norberto Quirno” (Cemic)Universidad De Buenos Aires. Hospital De Clínicas “José De San Martín”Conicet – Universidad De Buenos Aires. Unidad Ejecutora Idim-conicet (Ue Idim-conicet)Hospital General De Agudos Carlos G. DurandInstituto De Biología Y Medicina Experimental (Ibyme) ConicetConicet – Universidad De Buenos Aires. Unidad Ejecutora Idim-conicet (Ue Idim-conicet)Universidad De Buenos Aires. Instituto De Investigaciones Médicas Alfredo LanariConicet – Universidad De Buenos Aires. Unidad Ejecutora Idim-conicet (Ue Idim-conicet)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.http://dx.doi.org/10.1080/09537104.2021.1988547autoantibodiesmegakaryocytesplateletssystemic lupus erythematosusthrombocytopenia |
| spellingShingle | M. Constanza Baroni Pietto Paola R. Lev Ana C. Glembotsky Cecilia P. Marín Oyarzún Graciela Gomez Victoria Collado Cecilia Pisoni Ramiro A. Gomez Matías Grodzielski Jacqueline Gonzalez Karina V. Mariño Paula G. Heller Nora P. Goette Rosana F. Marta Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus Platelets autoantibodies megakaryocytes platelets systemic lupus erythematosus thrombocytopenia |
| title | Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus |
| title_full | Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus |
| title_fullStr | Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus |
| title_full_unstemmed | Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus |
| title_short | Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus |
| title_sort | pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus |
| topic | autoantibodies megakaryocytes platelets systemic lupus erythematosus thrombocytopenia |
| url | http://dx.doi.org/10.1080/09537104.2021.1988547 |
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