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

Abstract

Background: Idiopathic thrombocytopenic purpura (ITP) is associated with the cytokine response and dysregulation of the cytokine network. Gene polymorphisms of proinflammatory cytokines are associated with several diseases including ITP. Recently, the successful eradication of Helicobacter pylori has been reported to improve the platelet counts in some patients with ITP. The aim of this study was to elucidate the relationship between cytokine gene polymorphisms and platelet recovery in ITP patients after the eradication of H. pylori. Materials and Methods: Gastric H. pylori infection was confirmed using a culture method or specific IgG antibodies against H. pylori in the serum. Thirty-six adult H. pylori-positive ITP patients received antibiotic therapy for H. pylori. The response to treatment was defined as complete response (CR) if the platelet count was above 150 × 10³/µl and partial response (PR) if the platelet count increased by more than 50 × 10³/µl above the pretreatment count. Genomic DNA was extracted from peripheral blood and polymorphisms in IL-1B (–31, –511), IL-1RN (long or short), TNFA (–308) and TNFB (+252) were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Of the 36 ITP patients, twenty patients (responders) exhibited a platelet response after successful H. pylori eradication therapy, but the other patients (nonresponders) did not. There were no statistical differences in the frequencies of polymorphisms in IL-1B, IL-1RN and TNFA genes between responders and nonresponders. In contrast, the frequency of responders in ITP patients with the TNFB G/G or G/A genotype was significantly higher (69.6%) than that with the TNFB A/A genotype (30.8%). Conclusion: The TNFB (+252) G/G or G/A genotype may therefore be a good predictor of platelet recovery in ITP patients after the eradication of H. pylori.

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

“…In contrast, there was no significant difference in the relative frequencies of individual HLA alleles among H. pylori-infected and H. pylori-uninfected ITP patients and healthy controls in a Japanese study [10]. 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.…”

“…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].…”

Helicobacter pylori-associated immune thrombocytopenia: Clinical features and pathogenic mechanisms

“…The most consistently reported feature that predicts a favorable response is a shorter duration of ITP [9,49,50] , but other studies have not found this association [51][52][53] . Other clinical characteristics, including an age less than 65 when diagnosed with ITP [49] , a higher baseline platelet count [49] , no prior corticosteroid therapy [51] , no concomitant corticosteroid therapy [54,55] , and no prior therapy for ITP [49] , have been reported as factors predicting the platelet response, but other studies have reported conflicting results.…”

“…An association was shown between the HLA-DQB1*03 haplotypes and a higher probability of the platelet response [45] . Moreover, single nucleotide polymorphisms within the genes for tumor necrosis factor-β and an inhibitory Fcγ receptor ⅡB (FcγRⅡB) were found to be useful for predicting the response to the eradication treatment [55,56] . In terms of the anti-platelet autoantibody specificity, we found that the presence of an anti-GPIb autoantibody response predicts resistance to H. pylori eradication therapy.…”

Recent progress in understanding the pathogenesis of immune thrombocytopenia

“…For example, it appears that cytokine gene polymorphisms can be found in patients with ITP [54] and cytokine gene polymorphisms are associated with platelet recovery after Helicobacter pylori eradication therapy [55,56]. It also appears from recent studies that the methylation status of several proinflammatory genes may be a factor in whether they may be expressed in patients with ITP, and polymorphisms have been found in methyl transferase genes [57][58][59][60][61].…”