Dataset Information

Effect of Cytokine Gene Polymorphisms on Eltrombopag Reactivity in Japanese Patients with Immune Thrombocytopenia.

ABSTRACT:

Background

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts resulting from antiplatelet autoantibodies. Analysis of polymorphisms in cytokine-encoding genes is important for understanding the pathophysiology of ITP and selecting appropriate treatments. We investigated associations between polymorphisms in cytokine-encoding genes and responses to therapy in Japanese patients with ITP.

Methods

The participants in this study comprised 153 patients with ITP and 70 healthy controls. We extracted data on sex, age, platelet counts, bleeding symptoms, and therapeutic responses, including those to prednisolone (PSL) and eltrombopag. Genomic DNA was isolated from peripheral blood and polymorphisms in TNF-α, IL-10, TGF-β₁, and IFN-γ genes were analyzed using the PCR-SSP method.

Results

Our results showed that the TGF-β₁ +869 C/C genotype might be related to ITP in Japanese patients. The IL-10 -592 C/C and A/A, -819 C/C and T/T, and -1082, -819, -592 ATA/ATA genotypes might be associated with reactivity to PSL. Furthermore, the IL-10 -592 C/A -819 C/T genotypes, IL-10 ACC/ATA genotype, and TGF-β₁ +869 T/T and T/C genotypes might be linked to the response to eltrombopag.

Conclusion

Our results indicate that analysis of polymorphisms in cytokine-encoding genes could aid in understanding PSL and eltrombopag responsiveness in Japanese patients with ITP.

SUBMITTER: Nomura S

PROVIDER: S-EPMC8187034 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Immune thrombocytopenia (ITP) is an autoimmune disorder that induces a decrease in the number of circulating platelets due to spleen destruction and inability of megakaryocytes to restore normal counts. Immunosuppressive therapy with glucocorticoid drugs constitutes the first line of treatment. However, lack of response to these agents is not uncommon, and the management of refractory patients is a matter of controversy. In fact, day-to-day clinical practice shows that, in spite of the current guidelines, splenectomy, which is currently considered a suitable second-choice therapy, is being replaced by treatment with thrombopoietin receptor agonists. These boost platelet production by megakaryocytes. The use of one of these, namely eltrombopag, has been permitted for ITP patients refractory to first-line drugs or splenectomy, for the last 10 years. This review summarizes the experience reported using eltrombopag in ITP, paying attention to efficacy and safety. Results from clinical trials will be discussed, and studies performed in the course of daily clinical practice will also be reviewed, as these are useful to assess the potential of the drug in real-world settings. The management of adverse events and the use of eltrombopag in particular situations will also be covered. The experience reported so far permits us to suggest that eltrombopag efficiently induces recovery of platelet counts. Furthermore, recent papers have demonstrated that a sustained response after discontinuation, initially thought to be problematic, may be possible in a nonnegligible number of cases. The safety profile is satisfactory, although patients presenting with thromboembolism risk factors should be treated with caution until the eltrombopag-associated prothrombotic risk is fully established. In summary, although larger studies are still needed to clarify some issues, eltrombopag may be a useful alternative tool for ITP patients refractory to conventional medical management or splenectomy.