Abstract
Bystander immune suppression has been demonstrated in experimental models of oral immune tolerance induction. This phenomenon is associated with expression of transforming growth factor (TGF)-β1 and T-helper cell (Th) 2 cytokines. We have studied serum levels of Th cytokines and B- and T-lymphocyte subsets in chronic idiopathic thrombocytopenic purpura (ITP), a disorder in which the production of platelet autoantibodies might be caused by a cytokine network dysregulation. Forty-six patients with ITP were separated into three groups depending on the platelet count (pltc): (1) <50×109/l, (2) 50–150×109/l and (3) >150×109/l. We found significantly elevated plasma levels of the Th3 cytokine TGF-β1 in patients with pltc >150×109/l (23.5±2.8 ng/ml), compared with patients with pltc <50×109/l (2.3±0.6 ng/ml;P<0.0001), patients with pltc 50–150×109/l (7.2±1.7 ng/ml;P<0.0001) and healthy volunteers (9.8±1.3 ng/ml;P<0.01). The serum levels of the Th1 cytokines interleukin (IL)-2 and interferon (IFN)-γ were below the detection limits of the assays. Likewise, the Th2 cytokine IL-4 was not detectable or was very low both in patients and controls. The serum levels of IL-10, a Th2 cytokine, were within the assay range and patients with pltc <50×109/l had significantly lower levels (0.6±0.1 pg/ml) than both patients with pltc 50–150×109/l (1.8±0.1 pg/ml;P<0.005) and healthy volunteers (1.4±0.1 pg/ml;P<0.005). Furthermore, patients with pltc <50×109/l and splenectomised patients had significantly higher levels of CD4+CD25+ activated T cells [26.2±14.8% (P<0.05) and 26.7±11.9% (P<0.005), respectively] than healthy controls (16.5±4.0%). Also, the number of natural killer (NK) cells among patients with pltc >150×109/l were significantly elevated (26.6±16.0%;P<0.05) compared with controls (17.4±7.6%). In conclusion, our data corroborate previous findings of elevated numbers of activated T cells in chronic ITP patients with active disease, but neither a clear-cut Th1 nor a Th2 serum cytokine profile could be established. However, ITP in remission was associated with elevated TGF-β1, which might be a part of a bystander immune suppression. We propose that the effect of possible expression of TGF-β1 by oral immune tolerance induction deserves to be explored in ITP patients with an active disease.
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Received: 29 September 1999 / Accepted: 25 January 2000
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Andersson, P., Stockelberg, D., Jacobsson, S. et al. A transforming growth factor-β1-mediated bystander immune suppression could be associated with remission of chronic idiopathic thrombocytopenic purpura. Ann Hematol 79, 507–513 (2000). https://doi.org/10.1007/s002770000177
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DOI: https://doi.org/10.1007/s002770000177