Pathogenesis of immune thrombocytopenia
Résumé
Immune thrombocytopenia (ITP) is a rare autoimmune disease due to an abnormal T cell response, notably supported by splenic T follicular helper cells, that stimulates the proliferation and differentiation of autoreactive B cells. The antiplatelet autoantibodies they produce facilitate platelet phagocytosis by macrophages, essentially in the spleen. Macrophages contribute to the perpetuation of the auto-immune response as the main antigenpresenting cell during ITP. CD8 + T cells also participate to thrombocytopenia by increasing platelet apoptosis. Besides this peripheral platelet destruction, inappropriate bone marrow production also exacerbates thrombocytopenia, due to an immune response against megakaryocytes. Moreover, the level of circulating thrombopoietin, the main growth factor of megakaryocytes, is low during ITP. In this review, the major mechanisms leading to thrombocytopenia, the role of the different immune cells and the different targets of treatments are described.
Mots clés
HCV
hepatitis C virus
HIV
human immunodeficiency virus
IDO
3-dioxygenase
ITP
immune thrombocytopenia
MDS
myelodysplastic syndrome
MHC
major histocompatibility complex
moDC
monocyte-derived dendritic cells
MSC
mesenchymal stromal cells
RTX
rituximab
TCR
T cell receptor
TIMP-3
tissue inhibitor of metalloproteinase 3
TFH
T follicular helper cells
TLR
toll-like receptor
TPO
thrombopoietin
TPO-RA
thrombopoietin receptor agonists
TRAP
thrombin receptor activating peptide
Treg
Immune thrombocytopenia Platelets Pathogenesis T cells B cells Macrophages Dendritic cells Regulatory cells ADP
adenosine diphosphate AID
autoimmune diseases AML
acute myeloid leukemia APRIL
a proliferation inducing ligand BAFF
B cell activating factor Breg
regulatory B cells CMV
cytomegalovirus DC
dendritic cells EBV
Epstein Barr virus FcγR
Fcγ receptor GP
glycoproteins HCV
hepatitis C virus HIV
human immunodeficiency virus IDO
indoleamine 2
3-dioxygenase ITP
immune thrombocytopenia MDS
myelodysplastic syndrome MHC
major histocompatibility complex moDC
monocyte-derived dendritic cells MSC
mesenchymal stromal cells RTX
rituximab TCR
T cell receptor TIMP-3
tissue inhibitor of metalloproteinase 3 TFH
T follicular helper cells TLR
toll-like receptor TPO
thrombopoietin TPO-RA
thrombopoietin receptor agonists TRAP
thrombin receptor activating peptide Treg
regulatory T cells
adenosine diphosphate
AID
autoimmune diseases
AML
acute myeloid leukemia
APRIL
a proliferation inducing ligand
BAFF
B cell activating factor
Breg
regulatory B cells
CMV
cytomegalovirus
DC
dendritic cells
EBV
Epstein Barr virus
FcγR
Fcγ receptor
GP
glycoproteins
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