Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients

Gu, Hao; Xie, Xianju; Ma, Jingyao; Fu, Lingling; Ma, Jing; Wu, Runhui; Chen, Zhenping

doi:10.1097/mph.0000000000002483

Cited by 4 publications

(2 citation statements)

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“…SNPs in genes encoding immune checkpoint proteins (e.g. CD28, ICOS, PD1, DNAM1) have been associated with disease severity and steroid resistance 25 . However, the relevance of these findings to the development of rITP needs further investigation (reviewed in Ref.…”

Section: Genetics and ‘Syndromic’ Itpmentioning

confidence: 99%

Pathogenesis of refractory ITP: Overview

Cines

2023

Br J Haematol

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SummaryA subset of individuals with ‘primary’ or ‘idiopathic’ immune thrombocytopenia (ITP) who fail to respond to conventional first‐ and second‐line agents or who lose responsiveness are considered to have ‘refractory’ disease (rITP), placing them at increased risk of bleeding and complications of intensive treatment. However, the criteria used to define the refractory state vary among studies, which complicates research and clinical investigation. Moreover, it is unclear whether rITP is simply ‘more severe’ ITP, or if there are specific pathogenic pathways that are more likely to result in refractory disease, and whether the presence or development of rITP can be established or anticipated based on these differences. This paper reviews potential biological features that may be associated with rITP, including genetic and epigenetic risk factors, dysregulation of T cells and cytokine networks, antibody affinity and specificity, activation of complement, impaired platelet production and alterations in platelet viability and clearance. These findings indicate the need for longitudinal studies using novel clinically available methodologies to identify and monitor pathogenic T cells, platelet antibodies and other clues to the development of refractory disease.

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Section: Genetics and ‘Syndromic’ Itpmentioning

confidence: 99%

Pathogenesis of refractory ITP: Overview

Cines

2023

Br J Haematol

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“…Notably, a flow cytometry analysis of patients with ITP demonstrated a lowered interleukin (IL)-10 to IL-17 ratio in the GCR group (16). Additionally, one study using time-of-flight mass spectrometry (MS) analysis revealed that glucocorticoid-sensitive (GCS) individuals exhibited significantly higher levels of sirtuin 1 and hypoxia-inducible-factor 1A, suggesting a potential link to their favourable response to glucocorticoid therapy (17,18).…”

Section: Introductionmentioning

confidence: 99%

Predicting the efficacy of glucocorticoids in pediatric primary immune thrombocytopenia using plasma proteomics

Cao,

Zhu,

et al. 2023

Front. Immunol.

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ObjectivePrimary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder among children. While glucocorticoids are the primary first-line treatment for ITP treatment, they prove ineffective in certain patients. The challenge of identifying biomarkers capable of early prediction regarding the response to glucocorticoid therapy in ITP persists. This study aimed to identify ideal biomarkers for predicting glucocorticoid efficacy in patients with ITP using plasma proteomics.MethodsA four-dimensional data-independent acquisition approach was performed to determine the differentially expressed proteins in plasma samples collected from glucocorticoid-sensitive (GCS) (n=18) and glucocorticoid-resistant (GCR) (n=17) children with ITP treated with prednisone. The significantly differentially expressed proteins were selected for enzyme-linked immunosorbent assay validation in a cohort conprising 65 samples(30 healthy controls, 18 GCS and 17 GCR children with ITP). Receiver operating characteristics curves, calibration curves, and clinical decision curve analysis were used to determine the diagnostic efficacy of this method.Results47 differentially expressed proteins (36 up-regulated and 11 down-regulated) were identified in the GCR group compared with the GCS group. The significantly differentially expressed proteins myosin heavy chain 9 (MYH9) and fetuin B (FETUB) were selected for enzyme-linked immunosorbent assay validation. The validation results were consistent with the proteomics analyses. Compared with the GCS group, the GCR group exhibited a significantly reduced the plasma concentration of MYH9 and elevated the plasma concentration of FETUB. Furthermore, the receiver operating characteristics curves, calibration curves, and clinical decision curve analysis demonstrated good diagnostic efficacy of these validated biomarkers.ConclusionThis study contributes to the establishment of objective biological indicators for precision therapy in children with ITP. More importantly, the proteins MYH9 and FETUB hold potential as a foundation for making informed decisions regarding alternative treatments for drugresistant patients, thereby preventing treatment delays.

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