Clonally Expanded T-Cells in the Peripheral Blood of Patients with Idiopathic Thrombocytopenic Purpura and Helicobacter pylori Infection

Abstract

Eradication of Helicobacter pylori leads to platelet recovery in some patients with idiopathic thrombocytopenic purpura (ITP). Therefore, the pathogenesis of a subgroup of ITP is probably associated with H pylori infection (H pylori-related ITP). If H pylori-related ITP is a definite subgroup of ITP, specific oligoclonal T-cells might accumulate in the peripheral blood (PB). To address this issue, we performed single-strand conformation polymorphism analysis of complementarity-determining region 3 (CDR3) of the T-cell receptor beta-chain genes of PB T-cells. Fourteen ITP patients with H pylori infection and 12 ageadjusted healthy volunteers were studied. Of the 14 patients, 8 patients (responders) exhibited a platelet response after successful H pylori eradication therapy, but 6 patients (nonresponders) did not. Vbeta5.2, Vbeta15, and Vbeta19 gene usage by clonally expanded T-cells in PB obtained before H pylori eradication therapy was significantly higher in responders than in nonresponders or healthy volunteers (Vbeta5.2, P = .023; Vbeta15, P = .004; Vbeta19, P = .036). Furthermore, an abrogation of clonally expanded T-cells was observed after therapy in some responders. These findings suggest that specific T-cell clones accumulate in H pylori-related ITP and that such clones may be associated with immune-mediated destruction of platelets.

Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles

“…Peripheral blood T-cell clonality has been observed in patients with ITP and H pylori infection, prevailing in responder patients. 54 Peripheral blood B-and/or T-cell clonality has been noted in noninfected patients with ITP, with better response to therapy. 54,55 On the whole, the findings from our limited series do not suggest a clear role of B-and T-cell clonality in the pathogenesis of ITP associated with H pylori infection.…”

Association of Inflammatory Cytokine Gene Polymorphisms with Platelet Recovery in Idiopathic Thrombocytopenic Purpura Patients after the Eradication of Helicobacter pylori

“…Even though the exact pathogenetic mechanisms of H. pylori induced ITP remain obscure, H. pylori eradication is therefore now suggested to be a first-line therapy for H. pylori positive ITP patients in Japan as well as some other countries. Several studies have attempted to identify the predictive factors for platelet responses after the eradication of H. pylori in ITP patients, and have found some candidates, such as a shorter disease duration, high titers of anti-Cag A antibodies before H. pylori eradication, clonally expanded T cells in the peripheral blood and the level of atrophic gastritis [23,24,25,26]. Despite these extensive efforts, there have so far been few studies addressing the genetic backgrounds and platelet responses after the eradication of H. pylori .…”

Development of corpus atrophic gastritis may be associated with Helicobacter pylori-related idiopathic thrombocytopenic purpura

“…In addition, studies to determine the association of inflammatory cytokine gene polymorphisms, such as tumor necrosis factor and interleukin-1b, with H. pylori-induced ITP have also provided conflicting results [10,11]. Furthermore,the accumulation of specific T-cell clones in the peripheral blood [12] and a change in Fcc receptor balance on monocytes/macrophages [13] might be related to the pathogenesis of H. pylori-induced ITP. These results suggest that the mechanism of platelet recovery after H. pylori eradication is most likely multifactorial.…”

“…While the roles of H. pylori infection in ITP pathogenesis have been discussed from various standpoints [5][6][7][8][9][10][11][12][13], the mechanism of H. pylori-induced ITP remains unclear, and a useful predictor of platelet recovery has not been detected [14]. In our previous study, in which a platelet response was observed in 56% of H. pylori-infected Japanese adult patients with chronic ITP, there was no significant difference in clinical backgrounds between platelet responders and nonresponders to H. pylori eradication, although present corticosteroid therapy was slightly more common in nonresponders than in responders [15].…”