LTBP2 AS A BIOMARKER FOR EVALUATING THE RISK OF DEATH IN A DISEASED SUBJECT
The application discloses methods for treating a subject presenting with one or more signs of an inflammatory condition, or methods for evaluating the risk of death within a year for a subject presenting with one or more signs of an inflammatory condition, based on measuring the quantity of LTBP2 in a sample from the subject; and kits and devices for measuring LTBP2 and/or performing said methods.
1 . A method for treating a subject presenting with one or more signs of an inflammatory condition, said method comprising the steps of:
(i) obtaining a biological sample from the subject;
(ii) measuring the quantity of latent transforming growth factor beta binding protein 2 (LTBP2) in the sample;
(iii) comparing the quantity of LTBP2 measured in (ii) with a reference value of the quantity of LTBP2, said reference value representing a known risk of death;
(iv) predicting an increased risk of death within a year for the subject if the quantity of LTBP2 measured in (ii) substantially corresponds to a reference value representing a subject having an inflammatory condition which will decease within a year or if the quantity of LTBP2 measured in (ii) is elevated compared with a reference value representing a subject having an inflammatory condition which will survive within a year;
(vi) inferring from said increased risk of death within a year for the subject, a need for a therapeutic treatment or intervention in the subject; and
(vii) performing a therapeutic treatment or intervention in the subject.
2 . The method according to claim 1 , wherein the subject presenting with one or more signs of an inflammatory condition has sepsis or systemic inflammatory response syndrome (SIRS).
3 . The method according to claim 1 , wherein the subject presenting with one or more signs of an inflammatory condition has pulmonary inflammation.
4 . The method according to claim 1 , wherein the subject presenting with one or more signs of an inflammatory condition has undiagnosed acute dyspnea, acute heart failure, or renal dysfunction.
5 . The method according to claim 1 , for evaluating the risk of death within about 6 months, within about 5 months, within about 4 months, within about 3 months, within about 2 months, or within about one month, preferably within about one month.
6 . The method according to claim 1 , wherein the method further comprises measuring the presence or absence and/or quantity of one or more other biomarkers useful for evaluating the risk of death within a year in the sample from the subject.
7 . The method according to claim 6 , wherein said other biomarker is selected from the group consisting of ST-2, galectin-3, midregional pro-adrenomedullin, creatinine, Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), beta-trace protein, kidney injury molecule 1 (KIM-1), interleukin-18 (IL-18), B-type natriuretic peptide (BNP), pro-B-type natriuretic peptide (proBNP), amino terminal pro-B-type natriuretic peptide (NTproBNP) and C-reactive peptide, and fragments or precursors of any one thereof.
8 . The method according to claim 1 , wherein said sample is blood, serum, plasma or urine.
9 . The method according to claim 1 , wherein the subject is a critically ill patient.
10 . A method for evaluating the risk of death within a year for a subject presenting with one or more signs of an inflammatory condition, said method comprising the steps of:
(i) receiving data representative of values of the quantity of LTBP2 in a sample from the subject;
(ii) accessing a data repository on a computer, said data repository comprising a reference value of the quantity of LTBP2, said reference value representing a known risk of death, preferably a known risk of death within a year for a subject having an inflammatory condition; and
(iii) comparing the data as received in (i) with the reference value in the data repository on the computer, thereby making an evaluation of the risk of death within a year for the subject.
11 . A method for evaluating the risk of death within a year for a subject presenting with one or more signs of an inflammatory condition, said method comprising the steps of:
(i) obtaining a biological sample from the subject;
(ii) measuring the quantity of LTBP2 in said sample using an immunoassay or using a binding agent capable of specifically binding to LTBP2;
(iii) comparing the quantity of LTBP2 measured in (ii) with a reference value of the quantity of LTBP2, said reference value representing a known risk of death, preferably a known risk of death within a year for a subject having an inflammatory condition;
(iv) predicting an increased risk of death within a year in the subject if the quantity of LTBP2 measured in (ii) substantially corresponds to a reference value representing a subject having an inflammatory condition which will decease within a year or if the quantity of LTBP2 measured in (ii) is elevated compared with a reference value representing a subject having an inflammatory condition which will survive within a year.
12 . The method according to claim 11 , wherein the immunoassay employs an aptamer and/or antibody specifically binding to LTBP2.
13 . The method according to claim 11 , wherein the binding agent capable of specifically binding to LTBP2 is an aptamer or antibody specifically binding to LTBP2.
14 . The method according to claim 11 , wherein the subject presenting with one or more signs of an inflammatory condition has sepsis or SIRS.
15 . The method according to claim 11 , wherein the subject presenting with one or more signs of an inflammatory condition has pulmonary inflammation.
16 . The method according to claim 11 , wherein the subject presenting with one or more signs of an inflammatory condition has acute dyspnea, acute heart failure, or renal dysfunction.
17 . The method according to claim 11 , for evaluating the risk of death within about 6 months, within about 5 months, within about 4 months, within about 3 months, within about 2 months, or within about one month, preferably within about one month.
18 . The method according to claim 11 , wherein the method further comprises measuring the presence or absence and/or quantity of one or more other biomarkers useful for evaluating the risk of death in the sample from the subject.
19 . The method according to claim 18 , wherein said other biomarker is selected from the group consisting of ST-2, galectin-3, midregional pro-adrenomedullin, creatinine, Cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), beta-trace protein, kidney injury molecule 1 (KIM-1), interleukin-18 (IL-18), B-type natriuretic peptide (BNP), pro-B-type natriuretic peptide (proBNP), amino terminal pro-B-type natriuretic peptide (NTproBNP) and C-reactive peptide, and fragments or precursors of any one thereof.
20 . The method according to claim 11 , wherein said sample is blood, serum, plasma or urine.
21 . The method according to claim 11 , wherein the subject is a critically ill patient.
22 . The method according to claim 15 , for assessing the risk of dying within one month from a pulmonary cause or complication in the subject.
23 . A system for evaluating the risk of death within a year for a subject presenting with one or more signs of an inflammatory condition, said system comprising:
a computer data repository that comprises a reference value of the quantity of LTBP2, said reference value representing a known risk of death, preferably a known risk of death within a year for a subject having an inflammatory condition; and
a computer system programmed to access the data repository and to use information from the data repository in combination with information on the quantity of LTBP2 in a sample from a subject presenting with one or more signs of an inflammatory condition, to make an evaluation of the risk of death within a year for the subject.
24 . A kit comprising (i) means for measuring the quantity of LTBP2 in a sample from the subject, and preferably further comprising (ii) a reference value of the quantity of LTBP2 or means for establishing said reference value, wherein said reference value represents a known risk of death, preferably a known risk of death within a year for a subject having an inflammatory condition.
25 . The kit according to claim 24 , wherein the kit comprises one or more binding agents capable of specifically binding to LTBP2, preferably one or more aptamers or antibodies capable of specifically binding to LTBP2.
26 . The kit according to claim 24 , wherein the means for measuring the quantity of LTBP2 is an immunoassay, preferably an immunoassay employing antibody(ies) and/or aptamers, such as for example ELISA, RIA, or ELISPOT assay.
27 . A protein, polypeptide or peptide array or microarray comprising LTBP2, preferably a known quantity or concentration of LTBP2.
28 . A binding agent array or microarray comprising LTBP2, preferably a known quantity or concentration of LTBP2.