The present invention relates to the field of inflammatory bowel disease. More specifically, the present invention relates to the use of cytokines to detect, diagnose, and assess inflammatory bowel disease. In one embodiment, a method for diagnosing Crohn's Disease (CD) in a patient comprises the steps of (a) collecting a sample from the patient; (b) measuring the levels of at least one cytokine in the sample collected from the patient; and (c) comparing the levels of the at least one cytokine with predefined cytokine levels, wherein a correlation between the cytokine levels in the patient sample and predefined cytokine levels indicates that the patient has CD. In a specific embodiment, the at least one cytokine comprises Interferon (IFN)-gamma, Interleukin (IL)-1beta, IL-6, IL-8, IL-12, IL-17 and CXCL10.

Disclosed herein are methods of identifying biomarkers (such as genes (e.g., RNA or mRNA), proteins, and/or small molecules) that can be used to predict organ or tissue function or dysfunction. In some embodiments, the methods include ex vivo perfusion of the organ or tissue, collection of samples from the organ or tissue (for example, perfusate, fluids produced by the organ (such as bile or urine), or tissue biopsies) and measuring the level of one or more biomarkers in the sample. It is also disclosed herein that an analysis of biomarkers (such as genes (e.g., RNA or mRNA), proteins, and/or small molecules) present in a biological sample from an organ, tissue, or subject can be used to identify whether the organ, tissue, or subject is at risk for (or has) organ dysfunction or organ failure.

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 assays that detect one or more markers selected from the group consisting of Clusterin, Heart-type fatty acid binding protein, Hepatocyte growth factor, Interferon gamma, Interleukin-12 subunit beta, Interleukin-16, Interleukin-2, 72 kDa type IV collagenase, Matrix metalloproteinase-9, Midkine, and Serum amyloid P-component as diagnostic and prognostic biomarkers in renal injuries.

The disclosure provides biomarker proteins, a change in the concentration or activity level of which are associated with atypical hemolytic uremic syndrome (aHUS) or clinically meaningful treatment of aHUS with a complement inhibitor. Also provided are compositions and methods for interrogating the concentration and/or activity of one or more of the biomarker proteins in a biological fluid. The compositions and methods are useful for, among other things, evaluating risk for developing aHUS, diagnosing aHUS, determining whether a subject is experiencing the first acute presentation of aHUS, monitoring progression or abatement of aHUS, and/or monitoring response to treatment with a complement inhibitor or optimizing such treatment.

Methods for predicting cancer recurrence following a BCG immunotherapy are provided. In some aspects, cytokine levels from a patient are measured before and after a BCG therapy and the changes in cytokine levels are used to determine the risk of cancer lapse. Methods for selecting a patient for a further anti-cancer therapy are also provided.

Described herein are compositions for increasing IL-12 production comprising IgG or a fragment thereof or a variant thereof and uses of said compositions for treating cancer and infectious diseases. Also described herein are compositions for decreasing IL-12 production comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG and uses of said compositions for treating autoimmune diseases. Further described herein are methods for assessing efficacy of treatment by monitoring levels of various cytokines in the subject.

According to the present disclosure, optimization of treatment for a rejection reaction by immune tolerance induction is provided.

According to the present disclosure, there is provided a method for evaluating quality of a medicament for achieving immune tolerance, which is administered to a patient who has undergone living-donor liver transplantation, the method including: (a) a step of mixing and culturing peripheral blood lymphocytes collected from a patient before the living-donor liver transplantation and peripheral blood lymphocytes collected from a donor of the living-donor liver transplantation; (b) a step of mixing and culturing peripheral blood lymphocytes collected from the patient before the living-donor liver transplantation, peripheral blood lymphocytes collected from the donor of the living-donor liver transplantation, and the medicament for achieving immune tolerance in the patient; and (c) a step of measuring cytokine production in steps (a) and (b), in which in a case where the cytokine production in step (b) has changed compared to step (a), the medicament is considered to be a medicament for immune tolerance therapy.

The disclosure relates to methods for redirecting an active form of an endogenous cytokine to a target cell or target tissue of interest in a biological system or subject in need thereof by administering a multi-specific binding molecule comprising (a) a binding domain that specifically binds to an active form of a cytokine and (b) a binding domain that specifically binds to an epitope on a molecule that is a marker on a target cell or tissue, wherein the multi-specific binding molecule, when bound to the cytokine, does not block or only partially blocks, the ability of the cytokine to bind to and agonize a cognate receptor for the cytokine.

The disclosure relates to methods for redirecting an active form of an endogenous cytokine to a target cell or target tissue of interest in a biological system or subject in need thereof by administering a multi-specific binding molecule comprising (a) a binding domain that specifically binds to an active form of a cytokine and (b) a binding domain that specifically binds to an epitope on a molecule that is a marker on a target cell or tissue, wherein the multi-specific binding molecule, when bound to the cytokine, does not block or only partially blocks, the ability of the cytokine to bind to and agonize a cognate receptor for the cytokine.

Provided herein are methods, kits, and pharmaceutical compositions that include a PI3 kinase inhibitor for treating cancers or hematologic disorders.