Abstract: Compounds of formula (I) or pharmaceutically acceptable salts and/or solvates thereof. Also, the use of the compounds of formula (I) as immunomodulators and in the treatment of autoimmune diseases, transplanted organ rejection, graft-versus-host-disease and BOB1-related diseases, in which the compounds of formula (I) are administered to subjects in need thereof.

Abstract: Methods of diagnosing subclinical rejection, based on the level, amount or concentration of two genes, TCL1A and AKR1C3, whether independently from each other or in combination. When in combination, the level, amount or concentration of the two genes can further be combined with clinical parameters in the form of a composite score. Also, methods for treating subclinical rejection in a subject if/when the subject was diagnosed with subclinical rejection using the method of the invention; as well as a computer system and a kit-of-parts for implementing the method of diagnosing subclinical rejection.

Abstract: Some embodiments are directed to a prognostic method for determining whether a subject is at risk of having the CLAD, comprising: measuring the expression level of POU2AF1 or BLK in a biological sample obtained from the subject; comparing the expression level of POU2AF1 or BLK with a predetermined reference value and concluding that the subject is at risk of having CLAD when the expression level of POU2AF1 or BLK is lower than the predetermined reference value.

Abstract: The present invention relates to an in vitro method for determining the risk of occurrence of chronic lung graft dysfunction in a human subject comprising: a) measuring the level of CD9+ B cells in a blood sample of the subject, b) comparing the level of CD9+ B cells measured at step a) with one or more reference values of the level of CD9+ B cells, and c) determining the risk of occurrence of chronic lung graft dysfunction in the said subject from the comparison performed at step b).

Abstract: The present invention relates to a method for discriminating an operationally tolerant (TOL) subject from a non-operationally tolerant (STA) subject, comprising the following steps: i) establishing a composite score of tolerance (cSoT) with the expression levels of six genes in a biological sample obtained from said subject and two clinical parameters; wherein said six genes are ID3, AKR1C3, CD40, CTLA4, TCL1A and MZB1, and wherein said cSoT is established by the following formula: cSoT = ? i n ? = ? i × Exprs + ? test ? ? time × age test ? ? time + ? trans ? ? time × age trans ? ? time + intercept - scaling ? ? coefficient ii) comparing this cSoT with a predetermined reference value; and iii) concluding that the subject is TOL when the cSoT is higher than the predetermined reference value or concluding that the subject is STA when the cSoT is lower than the predetermined reference value.

Abstract: The present invention relates to a method for predicting the risk of having the CLAD in a subject by measuring the expression level of TCL1A in a biological sample obtained from said subject. Inventors have used a large-scale gene expression profiling of whole blood cells to identify early biomarkers of BOS. Microarray experiments performed from 80 patients (40 stable (STA) and 40 BOS) identified 47 genes differentially expressed between STA and BOS recipients. An independent set of patients (13 STA, 11 BOS) was then used for external validation by qPCR. T-cell leukemia/lymphoma protein 1A (TCL1A) gene was identified and validated as a predictive marker of BOS more than 6 months before diagnosis with area under curve of 0.77. Accordingly, the invention relates to a method for predicting the risk of having the chronic lung allograft dysfunction (CLAD) and to a method for preventing the risk of having CLAD by administering immunosuppressive drugs.

Abstract: Some embodiments are directed to a prognostic method for determining whether a subject is at risk of having the CLAD, comprising: measuring the expression level of POU2AF1 or BLK in a biological sample obtained from the subject; comparing the expression level of POU2AF1 or BLK with a predetermined reference value and concluding that the subject is at risk of having CLAD when the expression level of POU2AF1 or BLK is lower than the predetermined reference value.

Abstract: The present invention relates to a method for predicting the risk of having the CLAD in a subject by measuring the expression level of TCL1A in a biological sample obtained from said subject. Inventors have used a large-scale gene expression profiling of whole blood cells to identify early biomarkers of BOS. Microarray experiments performed from 80 patients (40 stable (STA) and 40 BOS) identified 47 genes differentially expressed between STA and BOS recipients. An independent set of patients (13 STA, 11 BOS) was then used for external validation by qPCR. T-cell leukemia/lymphoma protein 1A (TCL1A) gene was identified and validated as a predictive marker of BOS more than 6 months before diagnosis with area under curve of 0.77. Accordingly, the invention relates to a method for predicting the risk of having the chronic lung allograft dysfunction (CLAD) and to a method for preventing the risk of having CLAD by administering immunosuppressive drugs.

Abstract: Some embodiments are directed to a prognostic method for determining whether a subject is at risk of having the CLAD, comprising: measuring the expression level of POU2AF1 or BLK in a biological sample obtained from the subject; comparing the expression level of POU2AF1 or BLK with a predetermined reference value and concluding that the subject is at risk of having CLAD when the expression level of POU2AF1 or BLK is lower than the predetermined reference value.

Abstract: The invention relates to a method for predicting graft alterations in a transplanted patient, comprising a step of determining the expression levels of bactericidal/permeability-increasing protein (BPI), chemokine (C motif) ligand 1 (XCL1) and thioredoxin domain containing 3 (TXNDC3) genes in a biological sample obtained from said transplanted patient.

Abstract: The present invention relates to an in vitro method for determining the risk of occurrence of chronic lung graft dysfunction in a human subject comprising: a) measuring the level of CD9+ B cells in a blood sample of the subject, b) comparing the level of CD9+ B cells measured at step a) with one or more reference values of the level of CD9+ B cells, and c) determining the risk of occurrence of chronic lung graft dysfunction in the said subject from the comparison performed at step b).

Abstract: The present invention relates to a method for discriminating an operationally tolerant (TOL) subject from a non-operationally tolerant (STA) subject, comprising the following steps: i) establishing a composite score of tolerance (cSoT) with the expression levels of six genes in a biological sample obtained from said subject and two clinical parameters; wherein said six genes are ID3, AKR1C3, CD40, CTLA4, TCL1A and MZB1, and wherein said cSoT is established by the following formula: cSoT = ? i n ? = ? i × Exprs + ? test ? ? time × age test ? ? time + ? trans ? ? time × age trans ? ? time + intercept - scaling ? ? coefficient ii) comparing this cSoT with a predetermined reference value; and iii) concluding that the subject is TOL when the cSoT is higher than the predetermined reference value or concluding that the subject is STA when the cSoT is lower than the predetermined reference value.

Abstract: Some embodiments are directed to a prognostic method for determining whether a subject is at risk of having the CLAD, comprising: measuring the expression level of POU2AF1 or BLK in a biological sample obtained from the subject; comparing the expression level of POU2AF1 or BLK with a predetermined reference value and concluding that the subject is at risk of having CLAD when the expression level of POU2AF1 or BLK is lower than the predetermined reference value.

Abstract: The invention relates to a method for predicting graft alterations in a transplanted patient, comprising a step of determining the expression levels of bactericidal/permeability-increasing protein (BPI), chemokine (C motif) ligand 1 (XCL1) and thioredoxin domain containing 3 (TXNDC3) genes in a biological sample obtained from said transplanted patient.

Abstract: The invention concerns antibodies directed against CD127, I.e. the alpha chain of the receptor for interleukin7 (IL-7), especially the receptor for human IL-7 expressed on human cells (designated human IL-7R alpha or IL-7Ra) or the TSLP receptor. The antibodies of the invention have cytotoxic activity against CD127 positive cells. The invention also relates to the use of these antibodies in order to deplete subpopulations of T lymphocytes as a result of cytotoxic action of the antibodies, through ADCC and optionally through CDC. Accordingly the invention concerns the use of the antibodies in the treatment of transplant rejection, autoimmune diseases, allergic diseases, lymphoma or cancer when these pathologies are associated with CD127 positive cells.

Abstract: An in vitro method for determining the risk of occurrence of long-term kidney graft dysfunction in a subject comprising: a) measuring the level of CD8+ T cells having a phenotype CD45RA+/CD197?/CD27?/CD28? in a blood sample of the subject, b) comparing the level of CD8| T cells having a phenotype CD45RA|/CD197?/CD27?/CD28? measured at step a) with one or more reference values of the level of CD8+ T cells having a phenotype CD45RA+/CD197?/CD27?/CD28?, and c) determining the risk of occurrence of long-term kidney graft dysfunction in the said subject from the comparison performed at step b).

Abstract: Methods are provided for determining whether a subject has a graft tolerant phenotype. In practicing the subject methods, the expression of at least one gene in a sample from the subject, e.g., a blood sample, is assayed to obtain an expression evaluation for the at least one gene. The obtained expression evaluation is then employed to determine whether the subject has a graft tolerant phenotype. Also provides are compositions, systems and kits that find use in practicing the subject methods. The methods and compositions find use in a variety of applications, including the determination of an immunosuppressive therapy regimen.

Abstract: The invention concerns antibodies directed against CD127, I.e. the alpha chain of the receptor for interleukin7 (IL-7), especially the receptor for human IL-7 expressed on human cells (designated human IL-7R alpha or IL-7Ra) or the TSLP receptor. The antibodies of the invention have cytotoxic activity against CD127 positive cells. The invention also relates to the use of these antibodies in order to deplete subpopulations of T lymphocytes as a result of cytotoxic action of the antibodies, through ADCC and optionally through CDC. Accordingly the invention concerns the use of the antibodies in the treatment of transplant rejection, autoimmune diseases, allergic diseases, lymphoma or cancer when these pathologies are associated with CD127 positive cells.

Abstract: Methods are provided for determining whether a subject has a graft tolerant phenotype. In practicing the subject methods, the expression of at least one gene in a sample from the subject, e.g., a blood sample, is assayed to obtain an expression evaluation for the at least one gene. The obtained expression evaluation is then employed to determine whether the subject has a graft tolerant phenotype. Also provides are compositions, systems and kits that find use in practicing the subject methods. The methods and compositions find use in a variety of applications, including the determination of an immunosuppressive therapy regimen.

Abstract: The present invention relates to a method for detecting the presence or the absence, and optionally quantifying and/or isolating, antigen-specific peripheral blood mononuclear cells. This method, which involves flow cytometry, is based on the use of a fluorescently-labeled antibody specifically recognizing peripheral blood mononuclear cells, and of fluorescently-labeled beads coated with at least one antigen that is specifically recognized by antigen-specific peripheral blood mononuclear cells. The method according to the invention is for example useful for diagnosing immune disorders such as transplant rejections and autoimmune disorders.