Disturbed apoptosis of T-cells in patients with active idiopathic thrombocytopenic purpura

Bob Olsson; Per-Ola Andersson; Stefan Jacobsson; Lena Carlsson; Hans Wadenvik

doi:10.1160/TH04-06-0385

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(01): 139-144
DOI: 10.1160/TH04-06-0385

Platelets and Blood Cells

Schattauer GmbH

Disturbed apoptosis of T-cells in patients with active idiopathic thrombocytopenic purpura

Authors

Bob Olsson

¹Haematology Section, Göteborg University, Göteborg, Sweden, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
Per-Ola Andersson

¹Haematology Section, Göteborg University, Göteborg, Sweden, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
Stefan Jacobsson

³Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
Lena Carlsson

²RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
Hans Wadenvik

¹Haematology Section, Göteborg University, Göteborg, Sweden, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden

Abstract

Summary

Idiopathic thrombocytopenic purpura (ITP) is an organ specific autoimmune disorder in whichT-lymphocyte abnormalities have pathogenetic importance.In a DNA microarray screen of CD3+ T-lymphocytes from ITP patients and healthy controls we found an altered expression of genes associated with apoptosis, e.g. A20, caspase-8 and Bax.This together with our previous findings of increased gene expression of Fas,interferon-g and IL-2 receptor beta (IL2RB) indicated an altered activation induced cell death (AICD) of T-cells in ITP. Using a proliferation assay we found that CD3+ lymphocytes from ITP patients were significantly more resistant to dexamethasone induced suppression compared to normal lymphocytes.We also found that cultured CD3+ lymphocytes from ITP patients in remission were more susceptible to apoptosis both in the presence and absence of dexamethasone compared to cells from patient with active ITP and healthy controls, as indicated by increased staining of AnnexinV binding. Our findings suggest that apoptotic resistance of activated T-lymphocytes in patients with active ITP may lead to defective clearance of autoreactive T-lymphocytes through AICD, which might cause a continued immune destruction of platelets. Conversely, a loss of resistance to AICD in ITP patients in remission might be an important mechanism for the achievement of remission.

Keywords

Immune thrombocytopenia - T-cells - apoptosis - microarray - autoimmunity

Full Text

References

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