Significance of chemokines and soluble CD40 ligand in patients with autoimmune thrombocytopenic purpura

Abstract

We investigated the levels of various chemokines and soluble CD40L (sCD40L) in ITP patients, in order to determine the influence of CD40-CD40L interaction on the pathogenesis of ITP. We found increases in MCP-1 and RANTES levels in ITP patients compared with those in healthy individuals. Thirty-eight of the 65 ITP patients (58.5%) had elevated levels of sCD40L. We found significant decreases in platelet counts in sCD40L-positive ITP patients. Although the sCD40L level did not differ significantly between the control and nonimmune thrombocytopenia groups, but among ITP patients. sCD40L level was significantly higher in those with untreated ITP than in those with treated ITP. In addition, significant increases in RANTES, MCP-1, sCD14, and sP-selectin levels were observed in sCD40L-positive ITP patients, although sE-selectin levels were not increased in such patients. For other factors examined, however, there were no differences in level between sCD40L-positive and -negative ITP patients. These findings suggests that there are two groups of ITP patients, one with elevated and one with normal of sCD40L. ITP cases in which sCD40L was increased appeared to involve changes in platelet counts and monocyte activation. The pathogenesis of ITP may in some patients include alterations of the CD40/CD40L pathway.

Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents

“…3 Whereas healthy persons harbor platelet-specific autoreactive T cells that are tolerized in the periphery, 4 patients with ITP possess activated platelet-autoreactive T cells with increasing cytokine imbalance toward interleukin-2 (IL-2) and interferon-␥, [5][6][7][8][9] especially in patients with chronic ITP with some also reporting higher levels of circulating proinflammatory cytokines tumor necrosis factor-␣ 10 and soluble CD40 ligand (sCD40L). 11 These data are consistent with loss of peripheral tolerance and an inflammatory phenotype in chronic ITP patients.…”

“…These data further support a previous report 40 that platelets are not activated in patients on thrombopoietic agents. The reason why circulatory sCD40L, which are mostly platelet-derived, are higher in patients in our pretreatment group as well as in patients with low platelet counts 11 is not known, but it may be that sCD40L is derived from a nonplatelet source (eg, T cells) 41 in patients who have low platelet counts. In addition, the mechanisms that cause the release of sCD40L, but not TGF-␤1, in patients with low platelet counts remain to be fully determined, but it is possible that these cytokines may belong to different platelet granule sorting/release pathways.…”

Analysis of serum soluble CD40 ligand in patients with influenza virus-associated encephalopathy

“…Stimulation of these cell types through CD40 induces cell functions which contribute to inflammatory responses, including the expression of adhesion molecules, and also the release of proinflammatory cytokines, such as IL-6, IL1h, IL-8, IL-12, and TNF-a [19 -24]. Serum and plasma sCD40L levels are elevated in systemic lupus erythematosus [25,26], rheumatoid arthritis and associated vasculitis [27], mixed connective tissue disease [28], systemic sclerosis [29], cystic fibrosis [30], advanced squamous cancer of the lung [31], autoimmune thrombocytopenic purpura [32], and chronic idiopathic urticaria [33]. In these disorders, the importance and immunological mechanism of the CD40 -CD40L interaction have been discussed.…”

Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with systemic autoimmune diseases

“…The major sources of the soluble form of sCD40L are activated CD4 lymphocytes [14] and activated platelets [5]. Increased levels of sCD40L have been found in SLE [13,14], RA [39], systemic sclerosis [42], MCTD [43], IBD [10] and ITP [44]. Increased levels of sCD40L have been correlated with disease activity in SLE [14] and many studies have documented the effectiveness of anti-CD40L therapy in lupus nephritis at many murine models [26e29].…”