The Value of Interleukin-1β and Interleukin-33 Genetic Expression in the Pathogenesis and Differentiation of Primary ITP and SLE-Related Thrombocytopenia

Immune Thrombocytopenia, System; Lupus Erythematosus

gene expression, ITP, inflammation, autoimmune

Primary immune thrombocytopenia (ITP) is an autoimmune- mediated acquired bleeding disorder, defined as a platelet count less than 100×109/L without other causes of isolated thrombocytopenia. The etiology of ITP is complex and heterogeneous, and as no specific biomarkers are indicating its presence, ITP remains a diagnosis of exclusion. The heterogeneous nature of ITP is evident in the differences in clinical presentation and response to regular treatment among patients and the multiple mechanisms that have been forwarded to account for it, such as autoantibodies, T cell dysregulation, and impaired megakaryocytes. Except primary ITP, all forms of immune-mediated thrombocytopenia is defined as secondary ITP. Secondary ITP has several causes, including autoimmune diseases such as systemic lupus erythematosus

SLE is a complex autoimmune disease and is usually associated with hematological abnormality , including thrombocytopenia, the prevalence of which in SLE\\patients has been reported to be 7-30%. Conversely, the prevalence of SLE in all ITP cases in adults is approximately 5%, making SLE the most common cause of secondary ITP. In the early stages, when there are only thrombocytopenia symptoms, it is sometimes difficult to determine what form of ITP is present in patients with SLE. SLE-associated thrombocytopenia (SLE- TP) is defined as a platelet count less than 100×109/L in the absence of any other identifiable cause. The pathogenesis of thrombocytopenia in SLE is heterogeneous and multifactorial. However, it is widely accepted that an increased platelet clearance mediated by autoantibodies against platelets contributes to the pathogenesis, which is analogous to the mechanism of ITP. Differing from primary ITP, the clinical treatment for thrombocytopenia secondary to an identifiable cause is often targeted to the ongoing disorder. However, there are no specific biomarkers to differentiate SLE-TP from ITP. The family of interleukin (IL)-1 cytokines is a family of protein molecules consisting of 11 members, including IL-1α (IL-1F1), IL-1β (IL-1F2), IL-1 receptor antagonist (IL-1Ra, IL-1F3), IL-18 (IL-1F4), IL-36Ra (IL-1F5), IL- 36α (IL-1F6), IL-37 (IL-1F7), IL-36β (IL-1F8), IL-36γ (IL-1F9), IL-38 (IL-1F10), and IL-33 (IL-1F11). This cytokine family plays a crucial role as major proinflammatory and immunoregulatory mediators in a wide range of autoinflammatory, infectious, tumor, and autoimmune diseases that act through the receptors of the Toll-like/IL-1 receptor superfamily. The production of inflammatory cytokines such as IL-1, IL- 18, and IL-36 acts by activating target cells through the receptor superfamily then amplifying the immune response. However, antagonists such as IL-1Ra, the receptor antagonist of IL-1α and IL-1β, act as inhibitors of IL-1 dependent inflammation. The blocking of IL-1, particularly of IL-1β, has recently become the standard therapy for autoinflammatory diseases. Moreover, IL-1β, a driver of tumor-promoting inflammation in cancer, can be targeted in patients using an IL-1 receptor antagonist acting as a checkpoint inhibitor. Several studies have suggested abnormal changes in IL-18, and IL-18-binding protein (IL-18BP) were involved in the pathogenesis of SLE and ITP . Furthermore, recent studies demonstrate that IL-1 may also take part in inflammatory pathologies and auto-immune diseases by participating in the development of T-helper 17 (Th17) cells and increased numbers of Th17 cells have been reported in patients with SLE and ITP.

No related papers found yet.