Immune dysregulation in primary immune thrombocytopenia patients

Zhang, Jiakui; Zhang, Qiuye; Li, Yingwei; Tao, Lili; Wu, Fan; Shen, Yuanyuan; Tao, Qianshan; Xu, Xuanxuan; Wu, Chi; Ruan, Yanjie; Wang, Jiyu; Wang, Jeffrey; Wang, Yiping; Zhai, Zhimin

doi:10.1080/10245332.2018.1435021

Cited by 19 publications

(15 citation statements)

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“…CTLA4 is a specific regulatory T cells (Tregs), whose low expression means decreased Tregs. Similar result has been found in a recent study that pre-treated ITP patients present low levels of Tregs and NK cells [24]. Since the tagging SNPs in CTLA4 are not associated with ITP, the dysregulation of CTLA4 gene expression in ITP may not be driven by CTLA4 gene site mutation.…”

Section: Discussionsupporting

confidence: 89%

Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children

et al. 2018

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Objectives: To investigate the association of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) with immune thrombocytopenia (ITP). Methods: A case-control association analysis of 277 Chinese Han children was performed. The tagging variants rs11571315 and rs3087243 in the CTLA4 gene were detected using polymerase chain reaction-restriction fragment length polymorphism method. The expression quantitative trait loci (eQTL) analysis and quantitative real-time polymerase chain reaction were performed to determine the relationship of CTLA4 with ITP. Results: Neither SNP was significantly different between case and control groups in either the genotypic or allelic distribution. The eQTL analysis results indicated that in the spleen, the rs3087243 was significant with the expression of CTLA4. The rs11571315 has similar results. Interestingly, the transcript level of CTLA4 was found to significantly decrease in patients with ITP. Discussion: The autoimmune and gene etiology is implicated in the pathogen of ITP. The CTLA4 is important for negative regulation of T-cell activation, and CTLA-4 gene has been identified as a risk factor for some autoimmune diseases. However, association studies of ITP and CTLA4 gene have obtained conflicting results. This is the first study to systematically investigate the association of CTLA4 with ITP in Chinese Han children. Conclusions: The CTLA4 gene is suggested to correlate with ITP through its abnormal expression level instead of gene site mutation.

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Section: Discussionsupporting

confidence: 89%

Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children

et al. 2018

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“…Detection of Tregs. T cell subtypes including Tregs of all patients before treatment were evaluated with the method reported by our research team 41,42 . Two to five millilitre of PB was collected from each patient.…”

Section: Sino 19 Cell Infusion and Follow Upmentioning

confidence: 99%

Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia

Wang

Liu

et al. 2020

Nat Commun

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CD19-specific chimeric antigen receptor T cell (CD19 CAR T) therapy has shown high remission rates in patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL). However, the long-term outcome and the factors that influence the efficacy need further exploration. Here we report the outcome of 51 r/r B-ALL patients from a non-randomized, Phase II clinical trial (ClinicalTrials.gov number: NCT02735291). The primary outcome shows that the overall remission rate (complete remission with or without incomplete hematologic recovery) is 80.9%. The secondary outcome reveals that the overall survival (OS) and relapse-free survival (RFS) rates at 1 year are 53.0 and 45.0%, respectively. The incidence of grade 4 adverse reactions is 6.4%. The trial meets pre-specified endpoints. Further analysis shows that patients with extramedullary diseases (EMDs) other than central nervous system (CNS) involvement have the lowest remission rate (28.6%). The OS and RFS in patients with any subtype of EMDs, higher Tregs, or high-risk genetic factors are all significantly lower than that in their corresponding control cohorts. EMDs and higher Tregs are independent high-risk factors respectively for poor OS and RFS. Thus, these patient characteristics may hinder the efficacy of CAR T therapy.

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“…This breakdown in tolerance may be due to a quantitative and/or qualitative deficit of Tregs. Originating in the thymus, this CD4+ T-cell subpopulation constitutively and intensely expresses CD25, the α-chain of the IL-2 receptor [5,9], as well as the transcription factor forkhead box P3, which plays a primordial role in their genesis as well as in maintaining their peripheral immunosuppressive function. Whether a quantitative deficit of Tregs exists in ITP continues to be debated.…”

mentioning

confidence: 99%

“…Whether a quantitative deficit of Tregs exists in ITP continues to be debated. Some authors have observed a quantitative deficit in patients compared with control subjects [5,7,9]. This abnormal finding is reversed by corticosteroid therapy or rituximab [5].…”

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confidence: 99%

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Primary Immune Thrombocytopenia: A Translational Research Model for Autoimmune Diseases

Andrès

2019

JCM

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Immune dysregulation in primary immune thrombocytopenia patients

Cited by 19 publications

References 29 publications

Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children

Association of cytotoxic T-lymphocyte antigen 4 gene with immune thrombocytopenia in Chinese Han children

Influence of patient characteristics on chimeric antigen receptor T cell therapy in B-cell acute lymphoblastic leukemia

Primary Immune Thrombocytopenia: A Translational Research Model for Autoimmune Diseases

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