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

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 .