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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
JW Semple, Y Milev, D Cosgrave, M Mody, A Hornstein, V Blanchette and J Freedman
Division of Hematology, St Michael's Hospital, Toronto, Ontario, Canada.
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.
Volume 87,
Issue 10,
pp. 4245-4254,
05/15/1996
Copyright © 1996 by The American Society of Hematology
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