Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus

Summary

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.

Keywords:

• Autoantibodies
• megakaryocytes
• platelets
• systemic lupus erythematosus
• thrombocytopenia

Acknowledgements

The authors thank the staff of Obstetrics Department from Hospital Materno-Infantil Dr Gianantonio for collection of cord blood, to Daniela Ayala, Lorena Suarez and María de Los Ángeles Gargiulo for technical assistance, and to Gabriel A. Rabinovich and Santiago P. Méndez-Huergo for kindly providing PNA, MALII and SNA lectins. This work was supported by grants from Agencia Nacional de Promoción Científica y Tecnológica (PICT3607 and PICT1288).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

M.C.B.P. performed experiments, analyzed and interpreted data and discussed results; P.R.L, A.C.G, C.P.M.O. and M.G. performed experiments and discussed results; G.G, V.C, C.P, R.A.G. and J.G. provided patient samples and clinical data; K.V.M. provided reagents, analyzed and discussed results; P.G.H. contributed to study design, results discussion and manuscript preparation; N.P.G. contributed to study design, performed experiments, interpreted data and discussed results. R.F. M. designed and supervised the study, analyzed and interpreted data and prepared the manuscript. All authors contributed to manuscript editing and final approval.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the Fondo para la Investigación Científica y Tecnológica [PICT1288,PICT3607].