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Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura : relationship to platelet phenotype and antiplatelet T-cell reactivity

Semple, J. W. LU ; Milev, Y. ; Cosgrave, D. ; Mody, M. ; Hornstein, A. ; Blanchette, V. and Freedman, J. (1996) In Blood 87(10). p.4245-4254
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Acute Disease, Adult, Antigens, Human Platelet/analysis, Autoimmune Diseases/blood, Blood Platelets/immunology, Child, Chronic Disease, HLA-DR Antigens/analysis, Humans, Interferon-gamma/blood, Interleukin-10/blood, Interleukin-2/blood, Phenotype, Platelet Membrane Glycoproteins/analysis, Purpura, Thrombocytopenic, Idiopathic/blood, Single-Blind Method, T-Lymphocytes, Cytotoxic/immunology
in
Blood
volume
87
issue
10
pages
10 pages
publisher
American Society of Hematology
external identifiers
  • scopus:0029964421
  • pmid:8639783
ISSN
0006-4971
language
English
LU publication?
no
id
9cc3cfd3-9d96-4f35-90bc-6fd303c5104d
date added to LUP
2019-12-03 10:30:53
date last changed
2024-05-15 03:14:26
@article{9cc3cfd3-9d96-4f35-90bc-6fd303c5104d,
  abstract     = {{<p>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.</p>}},
  author       = {{Semple, J. W. and Milev, Y. and Cosgrave, D. and Mody, M. and Hornstein, A. and Blanchette, V. and Freedman, J.}},
  issn         = {{0006-4971}},
  keywords     = {{Acute Disease; Adult; Antigens, Human Platelet/analysis; Autoimmune Diseases/blood; Blood Platelets/immunology; Child; Chronic Disease; HLA-DR Antigens/analysis; Humans; Interferon-gamma/blood; Interleukin-10/blood; Interleukin-2/blood; Phenotype; Platelet Membrane Glycoproteins/analysis; Purpura, Thrombocytopenic, Idiopathic/blood; Single-Blind Method; T-Lymphocytes, Cytotoxic/immunology}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{10}},
  pages        = {{4245--4254}},
  publisher    = {{American Society of Hematology}},
  series       = {{Blood}},
  title        = {{Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura : relationship to platelet phenotype and antiplatelet T-cell reactivity}},
  volume       = {{87}},
  year         = {{1996}},
}