Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity.
Patients with both acute and chronic autoimmune thrombocytopenic purpura (AITP) have in vitro lymphocyte defects in the form of platelet-stimulated proliferation and cytokine secretion. A blinded study was performed to determine if these defects are related to serum cytokine levels and/or platelet antigen expression. Compared with controls, 53% of children with chronic AITP, but only 9% of those with acute AITP, had increased serum interleukin-2 (IL-2), interferon-gamma, and/or IL-10; however, none of the patients had detectible serum levels of IL-4 or IL-6, cytokine patterns suggesting and early CD4+ Th0 and Th1 cell activation. In children with chronic AITP, the levels of serum IL-2 correlated with in vitro platelet-stimulated IL-2 production. Few (17%) patients with AITP showed platelet activation, as measured by CD62 expression, or abnormal expression levels of platelet membrane glycoprotein (GP) IIbIIIa, but abnormal GPIb levels were observed in one-third of children with AITP. In contrast to normal controls and patients with nonimmune thrombocytopenia, a significant number of children with acute (80%), chronic (71%), or chronic-complex (55%) AITP and GPIb+ peripheral blood cells expressing HLA-DR. HLA-DR was variably coexpressed on distinct smaller and larger-sized GPIb+ cell populations with CD41, CD45, CD14, CD80, and/or glycophorin molecules. GPIb+ cells isolated from spleens of patients with chronic AITP had high expression (49% +/- 30%) of HLA-DR and splenic T cells had a high level of in vitro platelet-stimulated IL-2 secretion compared with controls. Platelet HLA-DR expression correlated inversely with platelet count, but not with therapy, serum cytokines, or in vitro lymphocyte antiplatelet reactivity. The results indicate that platelet HLA-DR expression is a common occurrence in patients with immune thrombocytopenia, whereas a large subpopulation of children with chronic AITP can be identified by increased serum cytokine levels and in vitro platelet-stimulated IL-2 secretion by lymphocytes, suggesting that differences exist in the immune pathogenesis of acute and chronic AITP, particularly at the level of platelet reactive T cells.
Semple
J W
JW
Division of Hematology, St Michael's Hospital, Toronto, Ontario, Canada.
Milev
Y
Y
Cosgrave
D
D
Mody
M
M
Hornstein
A
A
Blanchette
V
V
Freedman
J
J
D000208:Acute Disease; D000328:Adult; D016824:Antigens, Human Platelet / Q000032:analysis*; D001327:Autoimmune Diseases / Q000097:blood*; D001792:Blood Platelets / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002908:Chronic Disease; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood* / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood* / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood* / Q000378:metabolism; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood*; D016037:Single-Blind Method; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016824:Antigens, Human Platelet; D006684:HLA-DR Antigens; D007376:Interleukin-2; D010980:Platelet Membrane Glycoproteins; D016753:Interleukin-10; D007371:Interferon-gamma