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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

Bob Olsson
1   Haematology Section, Göteborg University, Göteborg, Sweden, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
,
Per-Ola Andersson
1   Haematology Section, Göteborg University, Göteborg, Sweden, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
,
Stefan Jacobsson
3   Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
,
Lena Carlsson
2   RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
,
Hans Wadenvik
1   Haematology Section, Göteborg University, Göteborg, Sweden, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden
› InstitutsangabenFinancial support: The study was supported by grants from the Swedish Medical Research Council (project no.: 14945, 11285, 13141), FoU Västra Götaland, Tore Nilsson’s Foundation for Medical Research, Åke Wiberg’s Foundation, Inga Britt and Arne Lundberg Research Foundation and the National Board for Health and Welfare.
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Publikationsverlauf

Received 21. Juni 2004

Accepted after resubmission 16. September 2004

Publikationsdatum:
14. Dezember 2017 (online)

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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
 

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