Autoimmune pathogenesis, immunosuppressive therapy and pharmacological mechanism in aplastic anemia

Int Immunopharmacol. 2023 Apr:117:110036. doi: 10.1016/j.intimp.2023.110036. Epub 2023 Mar 20.

Abstract

Acquired aplastic anemia (AA) is an autoimmune disease of bone marrow failure mediated by abnormally activated T cells, manifested by severe depletion of hematopoietic stem and progenitor cells (HSPCs) and peripheral blood cells. Due to the limitation of donors for hematopoietic stem cell transplantation, immunosuppressive therapy (IST) is currently an effective first-line treatment. However, a significant proportion of AA patients remain ineligible for IST, relapse, and develop other hematologic malignancies, such as acute myeloid leukemia after IST. Therefore, it is important to elucidate the pathogenic mechanisms of AA and to identify treatable molecular targets, which is an attractive way to improve these outcomes. In this review, we summarize the immune-related pathogenesis of AA, pharmacological targets, and clinical effects of the current mainstream immunosuppressive agents. It provides new insight into the combination of immunosuppressive drugs with multiple targets, as well as the discovery of new druggable targets based on current intervention pathways.

Keywords: Aplastic anemia; Autoimmune disease; Immunosuppressive therapy; Pharmacological mechanism; T cells.

Publication types

  • Review

MeSH terms

  • Anemia, Aplastic* / drug therapy
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Tissue Donors

Substances

  • Immunosuppressive Agents