Unravelling the role of the non-coding RNAs PVT1/miR-181a in orchestrating IL-23/RORγt and FOXP3/IL-10 axes in thrombocytopenia associated with systemic lupus erythematosus: insights into the clinical paradox of antiphospholipid syndrome.

INTRODUCTION: Thrombocytopenia is a frequent haematological complication among SLE patients and ranges from asymptomatic to severe, which over time could progress into bleeding. AIM: The current study explored the role of PVT1/miR-181a as an upstream regulator of FOXP3/RORγt and their associated interleukins in the pathogenesis of SLE-associated thrombocytopenia, and coexistence of antiphospholipid antibodies. METHODS: Sixty SLE patients with thrombocytopenia and forty without thrombocytopenia, together with forty healthy controls were recruited, and blood samples were drawn. The gene expression of PVT1, miR-181a, FOXP3, and RORγt were measured using RT-PCR, whereas the serum concentrations of IL-23, IL-10, lipocalin2, and MMP9 were measured using ELISA. RESULTS: The gene expression of miR-181a and RORγt were upregulated, PVT1 and FOXP3 were downregulated, levels of IL-23, lipocalin2, and MMP9 were increased, and IL-10 were lower among thrombocytopenic SLE patients relative to non-thrombocytopenic and healthy controls. Moreover, miR-181a and RORγt were upregulated, PVT1 and FOXP3 were downregulated, IL-23 level was increased, and IL-10 was decreased among thrombocytopenic SLE patients with positive antiphospholipid antibodies. CONCLUSION: Collectively, PVT1/miR-181a could be an upstream regulator of RORγt/FOXP3 and their associated pro-inflammatory and anti-inflammatory markers IL-10/IL-23 in the pathogenesis of SLE-associated thrombocytopenia. These biomarkers in a panel could be valuable in supporting the diagnosis of thrombocytopenia. Furthermore, understanding the role of the PVT1/miR-181a and RORγt/FOXP3 axes could be valuable in underscoring the co-existence of thrombocytopenia and antiphospholipid syndrome, thus holding the potential for monitoring the progression of associated bleeding and thrombosis risk and tailoring therapeutic interventions.