Multiple GWAS studies have shown that the SNP rs2281808 TT variant, present within the SIRPG gene, is associated with autoimmune diseases, such as type 1 diabetes. However, the role of SIRPγ in human T-cells is not known, neither is the functional significance of TT variant. Here we investigated SIRPG genotypes and their effects on the fate and function of human T-cells. We found that the presence of T variant resulted in reduction of SIRPγ expression on T-cells. Functionally, SIRPγlow CD8 T-cells in CT and TT individuals existed in a heightened effector state with lower activation threshold and had greater expression of genes and molecules associated with migratory and cytotoxic potential. Further, SIRPγlow CD8 T-cells were deficient in transcription factors associated with long-term functional memory formation. Our study reveals biological consequences of the SNP rs2281808 and provides novel insights into the potential mechanisms by which SIRPγ might regulate human immune responses.

BackgroundEndovascular treatment of intracranial aneurysms usually involves stent-assisted coiling (SAC) and flow diverters. Glycoprotein IIb/IIIa inhibitors such as tirofiban and dual antiplatelet therapy (DAPT) are required to prevent thromboembolic complications afterwards. We sought to determine the safety of tirofiban and DAPT in these cases.MethodsWe conducted a retrospective analysis of our database for patients with intracranial aneurysms who underwent SAC or flow diversion. The tirofiban-DAPT protocol used is described. Data regarding duration of infusion, placement of external ventricular devices (EVDs), complications, haemoglobin levels and platelet count before and 24 hours after antiplatelet therapy were collected and analysed.ResultsOne-hundred and forty-one patients with 148 aneurysms/procedures were included. 110 aneurysms were treated acutely and 38 electively. Minor and major haemorrhagic events were recognised in 20% (30/148) aneurysms. Only 5 (3.4%) intracerebral haemorrhages were symptomatic: 3 cortical/SAH and 2 EVD-related. The average blood volume in symptomatic haemorrhages was 24.8 cc versus 5.42 cc in asymptomatic haemorrhages (p=0.002). The rate of EVD-related haemorrhages was 15.7% (19/121) and only 2 (1.7%) were symptomatic. Most haemorrhagic events occurred in ruptured aneurysms (90.1%, p=0.01). No significant change in platelet count or haemoglobin levels before and 24 hours after administration of tirofiban and DAPT was documented. Concomitant administration of heparin did not increase haemorrhagic events.ConclusionThe use of the GP IIb/IIIa inhibitors tirofiban and DAPT in this series was safe. Tirofiban and DAPT did not affect platelet count or haemoglobin levels and did not increase rate of symptomatic haemorrhages or thromboembolic complications.