Autoimmune effector mechanisms associated with a defective immunosuppressive axis in immune thrombocytopenia (ITP)

Qizhao Li; Geneviève Marcoux; Yuefen Hu; Johan Rebetz; Li Guo; Elisabeth Semple; Drew Provan; Shuqian Xu; Ming Hou; Jung Peng; John W Semple

doi:10.1016/j.autrev.2024.103677

Autoimmune effector mechanisms associated with a defective immunosuppressive axis in immune thrombocytopenia (ITP)

Autoimmun Rev. 2024 Nov 6;23(12):103677. doi: 10.1016/j.autrev.2024.103677. Online ahead of print.

Authors

Qizhao Li¹, Geneviève Marcoux², Yuefen Hu³, Johan Rebetz², Li Guo⁴, Elisabeth Semple⁵, Drew Provan⁶, Shuqian Xu⁷, Ming Hou¹, Jung Peng¹, John W Semple⁸

Affiliations

¹ Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
² Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden.
³ Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
⁴ Bloodworks Northwest Research Institute, Seattle, USA; Division of Hematology and Oncology, University of Washington; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, USA.
⁵ Semple Scientific AB, Flyingeby, Sweden.
⁶ Department of Haematology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK.
⁷ Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, China. Electronic address: [email protected].
⁸ Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden; Clinical Immunology and Transfusion Medicine, Office of Medical Services, Region Skåne, Lund, Sweden; Departments of Pharmacology, Medicine and Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. Electronic address: [email protected].

PMID: 39515406
DOI: 10.1016/j.autrev.2024.103677

Abstract

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by an isolated thrombocytopenia and variable phenotype as some patients suffer no bleeding whilst others have bleeding from mild to severe, which may be fatal. This variability probably reflects the disease's complex pathophysiology; a dysregulated hyperreactive immune effector cell response involving the entire adaptive immune system (e.g. B and T cell subsets) that leads to platelet and megakaryocyte (MK) destruction. It appears that these effector responses are due to a breakdown in immune tolerance, and this is characterized by defects in several immunosuppressive cell types. These include defective T regulatory cells (Tregs), B regulatory cells (Bregs) and Myeloid-derived suppressor cells (MDSC), all of which are all intimately associated with antigen presenting cells (APC) such as dendritic cells (DC). The loss of this immunosuppressive axis allows for the activation of unchecked autoreactive T cells and B cells, leading to the development of autoantibodies and cytotoxic T cells (CTL), which can directly destroy platelets in the periphery and inhibit MK platelet production in the bone marrow (BM). This review will focus on the effector cell mechanisms in ITP and highlight the defective immunosuppressive axis that appears responsible for this platelet-specific immune hyperreactivity.

Keywords: Autoimmunity; B regulatory cells (Bregs); CD4+ T helper (Th) cells; Cytokines; Cytotoxic T cells (CTL); Immune thrombocytopenia; Myeloid derived suppressor cells (MDSC); Natural Killer (NK) cells; T regulatory cells (Tregs); Th1 cells; Th17 cell; Th17/Treg ratio; Th22 cells; Th9 cells; micro RNAs.

Publication types

Review