The present disclosure provides methods and compositions that find use in facilitating a diagnosis of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in a subject. The methods and compositions involve measurement of at least one of proteins: IL-16, IL-7, VEGF, CXCL9, CX3CL1, CCL24, CCL19, and CCL11 in a body fluid sample of a subject suspected of having CFS/ME. Levels of one or more of the aforementioned proteins can be used to facilitate a diagnosis of a CFS/ME and/or confirm a diagnosis of CFS/ME. The methods and compositions of the present disclosure also find use in screening subjects for clinical trials and facilitating treatment decisions for a subject.

Methods for treating coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, is described. The methods can be used to reduce the severity of outcomes related to COVID-19, such as hospitalization and ventilation. For example, treatment of a subject with a therapeutic agent that neutralizes interleukin 13 (IL-13) can result in reduced risk for mechanical ventilation in the subject. Also described are methods of predicting risk of mechanical ventilation in subjects with COVID-19.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Thymic stromal lymphopoietin, Vascular endothelial growth factor receptor 1, C-C motif chemokine 1, C-C motif chemokine 17, C-C motif chemokine 21, C-C motif chemokine 27, FLT-3 Ligand, Immunoglobulin G subclass 3, Interleukin-1 receptor type I, Interleukin-20, Interleukin-29, Interleukin-7, Platelet-derived growth factor A/B dimer, Platelet-derived growth factor A/A dimer, and MMP9:TIMP2 complex as diagnostic and prognostic biomarkers in renal injuries.

Disclosed herein is a T-helper cell (“T.sub.H-GM” cell) that is regulated by IL-7/STAT5 and which secrete GM-CSF/IL-3. Also disclosed are methods and compositions for modulating T.sub.H-GM function for the treatment of, e.g., inflammatory disorders. Diagnostic and prognostic methods for specifically identifying T.sub.H-GM-mediated inflammatory disorders (e.g., rheumatoid arthritis), as distinct from and/or in addition to non-T.sub.H-GM-mediated (e.g., TNF-α-mediated) inflammatory disorders, are also provided.

The present disclosure provides methods for detecting septic arthritis, transient synovitis, or osteomyelitis, based on protein signatures. Specifically, the method comprising: (i) measuring expression levels of one or more proteins in a biological sample obtained from the subject; (ii) determining a protein signature correlated with a detected disease based on the expression levels of the proteins in step (i); and (iii) assessing the occurrence or severity of the subject correlated with the disease based on the protein signature determined in step (ii). The methods may further comprise identifying suitable treatment for the patient based on the protein signatures.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using a one or more assays configured to detect a kidney injury marker selected from the group consisting of Thymic stromal lymphopoietin, Vascular endothelial growth factor receptor 1, C—C motif chemokine 1, C—C motif chemokine 17, C—C motif chemokine 21, C—C motif chemokine 27, FLT-3 Ligand, Immunoglobulin G subclass 3, Interleukin-1 receptor type I, Interleukin-20, Interleukin-29, Interleukin-7, Platelet-derived growth factor A/B dimer, Platelet-derived growth factor A/A dimer, and MMP9:TIMP2 complex as diagnostic and prognostic biomarkers in renal injuries.

The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. The invention includes methods of identifying a patient who would respond well to a T cell therapy or conditioning a patient prior to a T cell therapy so that the patient responds well to a T cell therapy. The conditioning involves administering one or more preconditioning agents prior to a T cell therapy and identifying biomarker cytokines prior to administering a T cell therapy.

The invention relates to antibodies directed against CD127, the alpha chain of the interleukin 7 (IL-7) receptor IL-7R), and which have antagonist properties for IL-7-IL-7R interaction, may present cytotoxic activity against CD127 positive cells but do not increase the maturation of dendritic cells (DCs) induced by TSLP, a cytokine also using CD127 as part of its receptor. Alternatively, or in addition, these antibodies do not induce the internalization of CD127 and/or inhibit the IL7-induced internalization of CD127. According to another aspect of the invention antibodies are provided which recognize a human CD127 epitope comprising sequences from the 2b site of CD127, in particular the epitope comprising comprises the human CD127 sequences of domain D1 and of the 2b site of CD127, in particular the epitope comprises at least one sequence from D1 comprising SEQ ID No: 115 (in particular comprising SEQ ID No: 110) and/or SEQ ID No: 111 and/or a sequence from the 2b site comprising the sequence of SEQ ID No: 116 and optionally also comprises SEQ ID No: 117 (in particular comprises SEQ ID No: 111). The antibodies of the invention are suitable for use in order to remedy to a condition diagnosed in a human patient which results from pathogenesis related to lymphopoiesis, when IL-7 signalling pathways provide contribution to said pathogenesis, especially when an increase in the maturation, more precisely the upregulation of costimulatory molecules, of dendritic cells is undesirable.

The invention relates to antibodies directed against CD127, the alpha chain of the interleukin 7 (IL-7) receptor IL-7R), and which have antagonist properties for IL-7-IL-7R interaction, may present cytotoxic activity against CD127 positive cells but do not increase the maturation of dendritic cells (DCs) induced by TSLP, a cytokine also using CD127 as part of its receptor. Alternatively, or in addition, these antibodies do not induce the internalization of CD127 and/or inhibit the IL7-induced internalization of CD127. According to another aspect of the invention antibodies are provided which recognize a human CD127 epitope comprising sequences from the 2b site of CD127, in particular the epitope comprising comprises the human CD127 sequences of domain D1 and of the 2b site of CD127, in particular the epitope comprises at least one sequence from D1 comprising SEQ ID No: 115 (in particular comprising SEQ ID No: 110) and/or SEQ ID No: 111 and/or a sequence from the 2b site comprising the sequence of SEQ ID No: 116 and optionally also comprises SEQ ID No: 117 (in particular comprises SEQ ID No: 111). The antibodies of the invention are suitable for use in order to remedy to a condition diagnosed in a human patient which results from pathogenesis related to lymphopoiesis, when IL-7 signalling pathways provide contribution to said pathogenesis, especially when an increase in the maturation, more precisely the upregulation of costimulatory molecules, of dendritic cells is undesirable.

Antibodies and antigen binding fragments that specifically bind to IL-7Rα are disclosed. Nucleic acids encoding the antibodies and antigen binding fragments, and vectors including the nucleic acid molecules are also provided. Methods for detecting a ca cancer or a cell that expresses IL-7Rα using the antibodies and antigen binding fragments are disclosed, as is the use of the antibodies and antigen binding fragments to prevent and/or treat a subject with a cancer that expresses IL-7Rα, such as acute lymphoblastic leukemia.