The present invention relates to novel methods for treating diseases and monitoring B cell levels in subjects and kit and compositions relating thereto by measuring serum BAFF levels in the subjects.

Disclosed are methods of isolating a TCR having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising: identifying one or more genes in the nucleic acid of a cancer cell of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence; inducing autologous APCs of the patient to present the mutated amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence; selecting the autologous T cells; and isolating a nucleotide sequence that encodes the TCR from the selected autologous T cells, wherein the TCR has antigenic specificity for the mutated amino acid sequence encoded by the cancer-specific mutation. Also disclosed are related methods of preparing a population of cells, populations of cells, TCRs, pharmaceutical compositions, and methods of treating or preventing cancer.

Disclosed herein are engineered monovalent binding proteins that bind to one or more antigens, as well as methods of making and using the binding proteins in the prevention, diagnosis, and/or treatment of disease.

Presented herein are systems and methods for developing classifiers useful for predicting response to particular treatments. For example, in some embodiments, the present disclosure provides a method of treating subjects suffering from an autoimmune disorder, the method comprising a step of: administering an anti-TNF therapy to subjects who have been determined to be responsive via a classifier established to distinguish between responsive and non-responsive prior subjects in a cohort who have received the anti-TNF therapy.

p53-upregulated modulator of apoptosis (PUMA) is a biomarker associated with islet cell health. If PUMA is low, islet cells are typically healthy. If PUMA is high, islet cells are typically unhealthy or dying. PUMA may be measured by either measuring its nucleic or amino acid. PUMA mRNA may be induced by TNF-α stimulation in a time- and dose-dependent manner and β cell apoptosis is induced through a mitochondrial pathway. TNF-α significantly inhibited glucose-induced preproinsulin precursor mRNA synthesis. Such β cell stress signaling in human islets indicates overall state of islet health and, ultimately, the risk of onset and/or degree of severity of both type 1 and type 2 diabetes mellitus.

Diagnostic screening tests that can be used to identify if a patient is a good candidates for an implantable vagus nerve stimulation device. One or more analyte, such as a cytokine or inflammatory molecule, can be measured from a blood sample taken prior to implantation of a vagus nerve stimulator to determine the patient's responsiveness to VNS for treatment of an inflammatory disorder.

Described is an assay for diagnosing an infection such as peritonitis in a subject. The assay includes a binding molecule, such as an antibody that specifically binds to an inflammatory marker in a sample from the subject, and a second binding molecule that binds to a marker indicative of a pathogen in the sample. For diagnosing peritonitis in a subject, the pathogen will be at least one bacterium and/or fungus. Typically, the assay will be incorporated into a lateral flow device and may include a binding molecule that specifically binds to an antigen indicative of the presence of a specific pathogen species. The described assay(s) may further include filter(s), enriching antigen(s), and buffer(s). Also described are methods of diagnosing and treating peritonitis in a subject who is a peritoneal dialysis patient that include utilizing the herein described assay(s) or assay kit(s) to analyze the subject's peritoneal dialysis effluent.

There is provided methods of determining tuberculosis (TB) infection status in an individual comprising: (i) providing a sample comprising T-cells; (ii) exposing the sample of (i) to one or more TB antigens; (iii) identifying T-cells in the sample that are CD4 positive and (a) secrete TNF-α without secreting IFN-γ; or (b) secrete IFN-γ without secreting TNF-α; (iv) identifying those cells of (iii) which are also CCR7 and, CD127 negative; and optionally (v) calculating the cells identified in (iv) as a percentage of those identified in (iii); wherein the identification of cells in (iv) and/or the percentage of T-cells calculated in (v) correlates to TB infection status of the individual, and wherein steps (iii) and (iv) can be carried out either sequentially or simultaneously. There are also provided compositions and kits for use in such methods.

The invention relates to method of diagnosis a subject suffering from Adult-onset Still's disease and further to determine the disease course of the subject suffering from Adult-onset Still's disease.

Presented herein are systems and methods for developing classifiers useful for predicting response to particular treatments. For example, in some embodiments, the present disclosure provides a method of treating subjects suffering from an autoimmune disorder, the method comprising a step of: administering an anti-TNF therapy to subjects who have been determined to be responsive via a classifier established to distinguish between responsive and non-responsive prior subjects in a cohort who have received the anti-TNF therapy.