Investigation of the influence of immune cells on aplastic anemia: a study based on genome-wide association studies data: immune cells on aplastic anemia

Abstract

Aplastic anemia(AA) is a non-neoplastic bone marrow failure syndrome characterized by the destruction of hematopoietic stem and progenitor cells, leading to a reduction in the production of all types of blood cells. This destruction is often caused by an abnormal immune response. This study aims to explore the association between 731 immunophenotypes and genetic susceptibility to AA. One AA-related GWAS dataset (ebi-a-GCST90018794) was obtained from the IEU OpenGWAS project. The ebi-a-GCST90018794 performed a GWAS on 473,500 European individuals with approximately 24,192,378 SNPs analyzed after quality control and imputation. GWAS summary statistics for each immune cell are publicly available from the European Bioinformatics Institute (accession numbers from GCST0001391 to GCST0002121). A total of 731 immunophenotypes were included. The Mendelian randomization analysis reported that 5 types of immune cells were associated with increased genetic susceptibility to AA. Inverse variance weighting (IVW) showed that CD127- CD8br T cell [odds ratio (OR), 1.135; 95% confidence interval (CI), 1.032–1.247; p = 0.009], CD25 on IgD+ CD38dim (OR, 1.053; 95% CI, 1.013–1.095; p = 0.0091), CD39+ resting Treg CD4 Treg (OR, 1.034; 95% CI, 1.010–1.059; p = 0.005), CD39+ secreting Treg AC (OR, 1.050; 95% CI, 1.013–1.089; p = 0.007), and CD8 on CD28+ CD45RA- CD8br (OR, 1.127; 95% CI, 1.044–1.215; p = 0.002) were associated with increased genetic susceptibility to AA. Conversely, 4 types of immune cells were associated with decreased genetic susceptibility to AA, including CD86 on CD62L+ myeloid DC [odds ratio (OR), 0.930; 95% confidence interval (CI), 0.882–0.981; p = 0.008], CD86+ plasmacytoid DC AC (OR, 0.923; 95% CI, 0.857–0.994; p = 0.034), DC AC (OR, 0.897; 95% CI, 0.838–0.960; p = 0.002), and DN (CD4-CD8-) NKT lymphocyte (OR, 0.926; 95% CI, 0.869–0.986; p = 0.017). This study explored the association between 731 immunophenotypes and genetic susceptibility to AA, identifying multiple immune cells associated with genetic susceptibility to AA. This provides a new perspective for the study of the pathogenesis of AA.