Abnormal γIFN and αTNF secretion in purified CD2+ cells from autoimmune thrombocytopenic purpura (ATP) patients: Their implication in the clinical course of the disease

Abstract

Gamma inferferon (gamma IFN), alpha tumor necrosis factor (alpha TNF), and interleukin 6 (IL-60) are cytokines produced by a wide variety of cells, including T lymphocytes and NK cells. These cytokines affect B-cell proliferation and differentiation into immunoglobulin secreting cells. In addition, gamma IFN and alpha TNF also enhance the function of macrophages, upregulating the expression of their IgG receptors. Abnormalities in the production of these cytokines may be involved in the clinical course of autoimmune thrombocytopenic purpura (ATP). This paper describes the production of these cytokines in PHA-stimulated peripheral blood CD2+ cells from ATP patients. Both gamma IFN and alpha TNF were significantly increased in PHA-stimulated CD2+ cells from therapy-dependent ATP patients (platelet counts < 50,000/microliter), as compared to ATP patients with stable disease (sustained platelet counts < 50,000/microliter without need treatment) (P < 0.05). No significant differences were found in gamma IFN production by PHA-stimulated CD2+ cells between therapy-dependent ATP patients and healthy controls (P < 0.05). However, the production of alpha TNF by PHA-stimulated CD2+ cells from therapy-dependent ATP patients was significantly higher compared to that found in healthy controls (P < 0.05). There were no significant differences in IL-6 production by PHA-stimulated CD2+ cells from ATP patients and healthy controls (P < 0.05). These findings demonstrate abnormal gamma IFN and alpha TNF secretion in purified CD2 cells from ATP patients. The clinical severity of the disease is associated with the altered secretion of these lymphokines by CD2 cells.

Comparison of platelet immunity in patients with SLE and with ITP

“…Since SLE is a systemic autoimmune disease while ITP is an organ-speci®c disease, these results could be interpreted to suggest that SLE has a Th2-like component [21,28,29] whereas organ-speci®c (or platelet-speci®c) autoimmunity has an immune response skewed towards a Th0/Th1-like activation pattern. This is consistent with previous observations [4,5]. The subjects with SLE-TP appeared to have a Th0/Th1-like phenotype similar to primary ITP, and this may be indicative of a changing pathophysiology in those SLE patients who have developed immune thrombocytopenia.…”

“…Lymphocyte proliferative abnormalities have been reported in some subjects with ITP [4,5,8]. Although lymphocyte proliferation in response to PHA and PWM was not signi®cantly dierent in any of the groups, only subjects with SLE-TP displayed signi®cantly enhanced (P`0X001) proliferation to the PKC activating agent PMA.…”

Human Platelet Antigens

“…136 In adults with chronic ITP, malignancy associated with ITP, or the autoimmune lymphoproliferation syndrome associated with defects in the Fas apoptosis pathway, there are elevated levels of IL-10, IL-11, IL-6, and IL-13. [137][138][139][140] One would expect that successful therapy might be associated with favorable changes in cytokine profiles.…”

Study of host immunity in patients with Helicobacter pylori-related idiopathic thrombocytopenia

“…In addition, IFN-γ and TNF-α also enhance the function of macrophages, upregulating the expression of their IgG receptors. Abnormalities in the production of these cytokines may be involved in the clinical course of autoimmune thrombocytopenic purpura [24]. The absence of platelet-specific antibodies in Group 2 may be explained by the requirement for a certain level of Th1 cytokines to elicit antibody production or perhaps the antibody titre is below the limit of detection.…”