INHIBITOR OF SURFACE PROTEIN (SP-D) / SIRPA / SHP2 PATHWAY FOR USE IN THE PREVENTION AND/OR TREATMENT OF SECONDARY INFECTION
The invention relates inhibitor of surface protein D (SP-D) and/or inhibitor of SP-D-SIRPα interaction for use in the prevention and/or the treatment of secondary disease, in particular nosocomial disease. The present invention also relates to pharmaceutical composition comprising inhibitor of surface protein D (SP-D) and/or inhibitor of SP-D-SIRPα interaction for use in the treatment of secondary infection. The present invention finds application in the therapeutic and diagnostic medical technical fields.
1 . A method for prevention and/or treatment of a secondary infection in a human comprising administering an effective amount of an inhibitor of surface protein D (SP-D) to the human.
2 . (canceled)
3 . The method of claim 1 , wherein the secondary infection is pneumonia, a pleural infection, a urinary infection, a peritoneal infection, an intra-abdominal abscess, meningitis, a mediastinal infection, a soft-tissue infection or a skin infection.
4 . The method of claim 1 , wherein the inhibitor of surface protein (SP-D) is an anti-SP-D antibody, an anti-SP-D antibody fragment, a recombinant anti-SP-D antibody, a binding peptide, or a siRNA.
5 . The method of claim 1 , wherein the effective amount of the inhibitor is from 0.1 to 100 μg.
6 . The method of claim 1 , wherein the inhibitor is administrated via a single injection or repeated injections for up to 28 days.
7 . (canceled)
8 . The method of claim 1 , wherein the inhibitor is administered at a level from 0.1 microg/kg to 1000 microg/kg per administration.
9 . An ex vivo method for determining the susceptibility to a secondary disease of a subject, comprising
a. determining the concentration(C s1 ) and/or expression level (L s1 ) of surface protein D (SP-D) in a biological sample of said subject, and
b. comparing of the measured concentration Cs1 and/or expression Ls1 with a corresponding reference value C sref and/or L sref .
10 . The method of claim 9 , wherein the biological sample is a sample of tracheal fluid, bronchoalveolar lavages, and/or pleural fluid.
11 . The method of claim 10 , wherein the concentration of SP-D is determined with an ELISA or RIA method.
12 . The method of claim 10 , wherein the reference value C sref is from 1 pg/mL to 1000 mg/mL.
13 . The method of claim 10 , wherein the reference value L sref is from 1 pg/mL to 1000 mg/mL.
14 . (canceled)
15 . A method for prevention and/or treatment of secondary infection in a human comprising administering an effective amount of an inhibitor of SP-D/SIRPα interaction to the human.
16 . (canceled)
17 . The method of claim 15 , wherein the secondary infection is pneumonia, a pleural infection, a urinary infection, a peritoneal infection, an intra-abdominal abscess, meningitis, a mediastinal infection, a soft-tissue infection or a skin infection.
18 . The method of claim 15 , wherein the inhibitor of SP-D/SIRPα interaction is a recombinant Anti-SFTPD Antibody.
19 . The method of claim 15 , wherein the effective amount of the inhibitor is from 0.1 to 100 μg.
20 . The method of claim 15 , wherein the inhibitor is administrated via a single injection or repeated injections for up to 90 days.
21 . A method for prevention and/or treatment of secondary infection in a human comprising an effective amount of an inhibitor of SHP 2 to the human.
22 . (canceled)
23 . The method of claim 21 , wherein the secondary infection is pneumonia, a pleural infection, a urinary infection, a peritoneal infection, an intra-abdominal abscess, meningitis, a mediastinal infection, a soft-tissue infection or a skin infection.
24 . The method of claim 21 , wherein the inhibitor of SHP 2 is a binding peptide, a siRNA, an antisense oligo, a ligand trap, a small molecule, or an antibody.
25 . The method of claim 21 , wherein the effective amount of the inhibitor is from about 0.01 to 2000 mg.
26 . The method of claim 21 , wherein the inhibitor is administrated via a single injection or repeated injections for up to 90 days.
27 . An ex vivo method for determining the susceptibility to a secondary disease of a subject, comprising
a. determining the concentration (C a1 ) and/or expression level (L a1 ) of SIRPα in a biological sample of said subject, and
b. comparing of the measured concentration C a1 and/or expression L a1 with a corresponding reference value C aref and/or L aref .
28 . The method of claim 27 , wherein the biological sample is a sample of tracheal fluid, bronchoalveolar lavages, pleural fluid and/or circulating leukocytes.
29 . The method of claim 27 , wherein the reference value C aref is from 1 pg/mL to 100 mg/mL.
30 . The method of claim 27 , wherein the reference value L aref is from 0 to 100 ratio of house-keeping gene (PCR) or from 10 to 80% positive cells (flow cytometry).
31 . (canceled)