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.