Abstract: Sickle cell disease (SCD) is a single gene disorder characterized by mutant hemoglobin-S (HbS) and chronic intravascular haemolysis. Painful vaso-occlusive crises (VOC) are typical of SCD and often associated to a further rise in hemolysis. VOC is the clinically painful form of vaso-occlusion, that is due to the aggregation of red blood cells in the capillaries and venules. Such event is promoted or aggravated by adhesion of polymorphonuclear neutrophils (PMNs) to red blood cells and the endothelium leading to tissue ischemia, inflammation and imperfect repair. Repeated vaso-occlusion and PMNs interactions with the vascular endothelium are thought to promote microvascular injuries in SCD patients. The inventors tested the effect of pharmacological inhibition of TREM-1 with LR12 peptide in two experimental vaso-occlusive crisis models. Additional validation of TREM-1 involvement in vaso-occlusion was verified using mice with sickle cell disease and Trem-1 gene deficiency.

Abstract: The present disclosure relates to a method of treating an acute inflammatory disorder such as septic shock in a subject in need thereof. The method involves administering to a subject who has a soluble TREM-1 (sTREM-1) level measured in a biological sample from the subject greater than a predetermined sTREM-1 value an amount of a TREM-1 inhibitor sufficient to treat the inflammatory disorder.

Abstract: Novel anti-TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) antibodies and antigen-binding fragments thereof. Also, fusion proteins that include these anti-TREM-1 antibodies and antigen-binding fragments thereof, as well as the therapeutic uses thereof for treating of a disease, such as an inflammatory or autoimmune disease, a cardiovascular disease, a cancer, or an infectious disease.

Abstract: The use of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as a marker in a method for identifying a subject suffering from a disease caused by a coronavirus such as COVID-19 at risk of having or developing a severe form and/or a complication or at risk of death, in a method for assessing the severity of a disease caused by a coronavirus such as COVID-19, and in a method for monitoring a subject suffering from a disease caused by a coronavirus such as COVID-19.

Abstract: An inhibitor of triggering receptor expressed on myeloid cells 1 (TREM-1) for use in the treatment of coronavirus disease 2019 (COVID-19) in a subject in need thereof, in particular in a subject suffering from a severe form and/or a complication of COVID-19. Also, the use of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as a marker in a method for identifying a subject suffering from COVID-19 susceptible to respond to a TREM-1 inhibitor and in a method for monitoring the effectiveness of TREM-1 inhibitor administered to a subject suffering from COVID-19.

Abstract: A method for identifying human subjects suffering from an inflammatory disorder susceptible to respond to a therapy, in particular to a TREM-1 inhibitor. In particular, an in vitro method for identifying a human subject suffering from an inflammatory disorder, preferably an acute inflammatory disorder such as SIRS, sepsis or septic shock, susceptible to respond to a therapy, in particular to a TREM-1 inhibitor. The method includes the steps of a) measuring the level of soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) in a biological sample from the human subject, comparing the level of sTREM-1 measured at step a) to a predetermined sTREM-1 value, and c) identifying a human subject suffering from an inflammatory disorder with a level of sTREM-1 measured at step a) higher than the predetermined sTREM-1 value of step b) as susceptible to respond to a therapy, in particular to a TREM-1 inhibitor.

Abstract: A cardiovascular event or disease is prevented or treated in a subject by measuring the expression level of soluble Triggering Receptors Expressed on Myeloid cells-1 (sTREM-1) level in a sample from the subject and comparing it to a reference level. Based on this comparison, subjects that are at risk of having or developing a cardiovascular event or disease are identified, and administered a suitable therapy.