The Expression of Immune Checkpoint CD28 rs1980422-related Single-nucleotide Polymorphisms in the Primary Immune Thrombocytopenia

The Expression of Immune Checkpoint CD28 rs1980422-related Single-nucleotide Polymorphisms in the Primary Immune Thrombocytopenia

Primary immune thrombocytopenia (ITP), one of the most common bleeding disorders, is characterized by reduced platelet count and an increased risk of bleeding ITP is an acquired autoimmune disease, in which platelets are opsonized by auto-antibodies and destroyed by phagocytic cells ITP pathogenesis involves a hyper-activated T cell response, which is important for cell-mediated cytotoxicity and IgG production Therefore, investigating T cell abnormalities in ITP patients may reveal the mechanism of pathogenesis and development of ITP.

The costimulatory molecules of T cells consist of CD28, inducible costimulatory (ICOS), TNF superfamily member 4 (TNFSF4), and DNAM1 (CD226), and the co-inhibitory molecules contain TIM3, cytotoxic T-lymphocyte associated protein 4 (CTLA4), programmed death-1 (PD1), and lymphocyte activating 3 (LAG3) Among these, CD28 and CTLA4 represent the best-studied costimulatory pathways. CD28 and CTLA4 interact with two ligands (CD80 and CD86) on the surface of antigen-presenting cells (APCs), introducing a positive stimulatory and a negative inhibitory signal into T cells, respectively

Inclusion Criteria:

• approval to sign an informed written consent
• patient with newly diagnosed ITP
• platelet count of peripheral blood < 100×109/ L on at least two consecutive routine blood tests, normal or increased megakaryocyte count in bone marrow (as previously diagnosed)
• no other disease or condition related to thrombocytopenia
• patient age > 1 year and < 65 years

Exclusion Criteria:

• Refusal to sign an informed written consent
• Patients with other autoimmune or hemorrhagic diseases (e.g., SLE, severe anemia), or thrombocytopenia due to pregnancy, viruses (e.g., hepatitis C virus, human immunodeficiency virus)
• active infections
• vaccinations, or drugs (e.g., heparin) .