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 purpu ra (AITP) have in vitro lymphocyte defects in the form of platelet-sti mulated proliferation and cytokine secretion. A blinded study was perf ormed to determine if these defects are related to serum cytokine leve ls 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 I L-6, cytokine patterns suggesting an early CD4(+) Th0 and Th1 cell act ivation. In children with chronic AITP, the levels of serum IL-2 corre lated with in vitro platelet-stimulated IL-2 production. Few (17%) pat ients with AITP showed platelet activation, as measured by CD62 expres sion, or abnormal expression levels of platelet membrane glycoprotein (GP) IIbIIIa, but abnormal GPIb levels were observed in one-third of c hildren with AITP. In contrast to normal controls and patients with no nimmune thrombocytopenia, a significant number of children with acute (80%), chronic (71%), or chronic-complex (55%) AITP had GPIb(+) periph eral 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 isolate d 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 pl atelet-stimulated IL-2 secretion compared with controls. Platelet HLA- DR expression correlated inversely with platelet count, but not with t herapy,serum cytokines, or in vitro lymphocyte antiplatelet reactivity . The results indicate that platelet HLA-DR expression is a common occ urrence in patients with immune thrombocytopenia, whereas a large subp opulation of children with chronic AITP can be identified by increased serum cytokine levels and in vitro platelet-stimutated IL-2 secretion by lymphocytes, suggesting that differences exist in the immune patho genesis of acute and chronic AITP, particularly at the level of platel et reactive T cells. (C) 1996 by The American Society of Hematology.