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 mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here the inventors show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and ?1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions.

Abstract: The present invention relates to the prevention and the treatment of extracapillary glomerulonephritis such as rapidly progressive glomerulonephritis and collapsing glomerulonephritis.

Abstract: The present invention relates to methods for determining the risk of severe complications in hemolytic diseases. The present invention relates to a method for determining whether a patient suffering from sickle cell disease is at risk for a vaso-occlusive crisis comprising the steps consisting of i) determining the level of cell microparticles in a blood sample obtained from said patient and ii) determining the level of heme and/or hemoglobin contained in said cell microparticles. The present invention also relates to a method for a method the severe complication in hemolytic diseases comprising the steps consisting of i) determining the level of cell microparticles in a blood sample obtained from said patient and ii) determining the level of heme and/or hemoglobin contained in said cell microparticles.

Abstract: The present invention relates to the prevention and the treatment of rapidly progressive glomerulonephritis.

Abstract: The present invention relates to the prevention and the treatment of rapidly progressive glomerulonephritis.

Abstract: The present invention relates to the prevention and the treatment of extracapillary glomerulonephritis such as rapidly progressive glomerulonephritis and collapsing glomerulonephritis.

Abstract: The present invention relates to the prevention and the treatment of extracapillary glomerulonephritis such as rapidly progressive glomerulonephritis and collapsing glomerulonephritis.

Abstract: The present invention relates to the prevention and the treatment of extracapillary glomerulonephritis such as rapidly progressive glomerulonephritis and collapsing glomerulonephritis.

Abstract: The present invention relates to methods for determining the risk of severe complications in hemolytic diseases. The present invention relates to a method for determining whether a patient suffering from sickle cell disease is at risk for a vaso-occlusive crisis comprising the steps consisting of i) determining the level of cell microparticles in a blood sample obtained from said patient and ii) determining the level of heme and/or hemoglobin contained in said cell microparticles. The present invention also relates to a method for a method the severe complication in hemolytic diseases comprising the steps consisting of i) determining the level of cell microparticles in a blood sample obtained from said patient and ii) determining the level of heme and/or hemoglobin contained in said cell microparticles.

Abstract: The present invention relates to methods for producing a non human animal model for aortic aneurysm which could provide insight into the diagnosis and treatment of disease. Furthermore, the present invention relates to methods and compositions for the treatment or the prevention of aneurysm in a subject in need thereof.

Abstract: The present invention relates to TG2 inhibitors for use in the prevention or treatment of rapidly progressive glomerulonephritis and to pharmaceutical compositions thereof.

Abstract: The present invention relates to endothelin inhibitors for use in the treatment of Rapidly Progressive GlomeruloNephritis and to pharmaceutical compositions thereof.

Abstract: The present invention relates to uses, methods and compositions for treating immune-mediated glomerulonephritis, such as crescentic glomerulonephritis. More specifically, the invention relates to the use of an EFGR antagonist or of an inhibitor of EGFR or HB-EGF expression for the treatment of said diseases.

Abstract: The present invention relates to methods for producing a non human animal model for aortic aneurysm which could provide insight into the diagnosis and treatment of said disease. Furthermore, the present invention relates to methods and compositions for the treatment or the prevention of aneurysm in a subject in need thereof.

Abstract: The present invention relates to uses, methods and compositions for treating immune-mediated glomerulonephritis, such as crescentic glomerulonephritis. More specifically, the invention relates to the use of an EFGR antagonist or of an inhibitor of EGFR or HB-EGF expression for the treatment of said diseases.