Abstract
ABSTRACTObjectives: 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.
Highlights
Immune thrombocytopenia (ITP), one of the most common hematologic disorders in children, is an acquired organ-specific autoimmune hemorrhagic disease resulting in bleeding and a mortality rate of about 4% per year [1]
Autoreactive B lymphocytes are viewed as the primary immunologic defect, dysfunction of T cells plays important roles in the pathophysiology of ITP based on the following evidences: 1. Autoantibody production in ITP is associated with both T-B cognate interaction and T-cell activation; 2
In order to investigate the associations of the CTLA-4 gene polymorphisms with ITP, we explored the CTLA4 variants using 1000 genome data and performed a case–control association analysis with selected tagging SNPs in Chinese children
Summary
Immune thrombocytopenia (ITP), one of the most common hematologic disorders in children, is an acquired organ-specific autoimmune hemorrhagic disease resulting in bleeding and a mortality rate of about 4% per year [1]. The clinical features of ITP are decreased platelet counts in the absence of any obvious cause and emerging of anti-platelet autoantibodies which mediate platelet destruction [2]. ITP is usually chronic in adults, while in children, most cases are acute with short duration and spontaneous remission occurring in six months. About 20% of children acute ITP cases become chronic (>six months) [3]. The etiology of ITP is not clear yet. Autoreactive B lymphocytes are viewed as the primary immunologic defect, dysfunction of T cells plays important roles in the pathophysiology of ITP based on the following evidences: 1. Autoantibody production in ITP is associated with both T-B cognate interaction and T-cell activation; 2.
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