Tandem P-selectin glycoprotein ligand immunoglobulin (TSGL-Ig) prevents lung vaso-occlusion in Sickle Cell Disease mice.

Abstract Sickle cell disease (SCD) is a monogenic disorder, estimated to affect over three million people worldwide1,2. Acute systemic painful vaso-occlusive episode (VOE) is the primary reason for emergency medical care among SCD patients3. VOE may also progress to acute chest syndrome (ACS), a type of acute lung injury and one of the primary reasons for mortality among SCD patients3. Recently, P-selectin monoclonal antibodies were shown to attenuate VOE in SCD patients and lung vaso-occlusion in transgenic humanized SCD mice, highlighting the therapeutic benefit of P-selectin inhibition in SCD4,5. Here, we use quantitative fluorescence intravital lung microscopy (qFILM) to show that tandem-P-selectin-glycoprotein-ligand-immunoglobulin (TSGL-Ig) fusion molecule containing four P-selectin binding sites, significantly attenuated intravenous (IV) oxy-hemoglobin (oxy-Hb) triggered lung vaso-occlusion in SCD mice. These findings highlight the therapeutic potential of TSGL-Ig to prevent VOE and ACS in SCD.