The disclosed embodiments concern methods, devices, and systems for identifying candidate biomarkers useful for the diagnosis, prognosis, monitoring and screening and/or as targets for the treatment of diseases and conditions in subjects, in particular autoimmune and infectious diseases. The identification of candidate biomarkers is predicated on identifying discriminating peptides present on a peptide array, which can distinguish samples from different subjects having different health conditions by the binding patterns of antibodies present in the samples.

The present inventors identified a subpopulation of genes induced by type I and type II IFNs in a human submandibular gland (HSG) epithelial cell line. Unexpectedly, it was found that the majority of genes that are highly up-regulated by IFN-α are also highly induced by IFN-γ. In contrast, there was a substantial group of genes that are highly induced by IFN-γ only. In target tissues, this identified subpopulation of genes and probes allow different IFN patterns to be discerned, enabling more precise molecular classification of patient subpopulations. The identified gene probes are useful for selecting and monitoring therapy, and for defining efficacy of novel agents in the autoimmune rheumatic diseases.

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.

A new quantification method for measuring citrulline, which has an association with various diseases and is a biomarker particularly useful for early diagnosis of rheumatoid arthritis, an enzyme for quantification, a composition for quantification, and a kit for quantification are provided. A quantification method of citrulline is provided by adding a citrulline oxidoreductase to a sample. The oxidoreductase is an oxidase, and a concentration of the citrulline may be determined by quantifying hydrogen peroxide produced by addition of the oxidase. A concentration of the citrulline may be determined by reacting a reagent with hydrogen peroxide produced by addition of the oxidase.

The present disclosure provides methods of evaluating a subject, e.g., a subject at risk for or suffering from a pKal-mediated or bradykinin-mediated disorder, based on values (e.g., percentages) of intact and/or cleaved kininogen in a sample of the subject. Provided methods permit analysis of patients with plasma kallikrein-mediated angioedema (KMA), or other diseases mediated by pKal useful in the evaluation and treatment. Such methods can involve the use of a detection agent that preferentially binds cleaved kininogen or intact kininogen.

The present invention provides a method for diagnosing or detecting an autoimmune disease in an individual, the method comprising or consisting of the steps of (a) providing a sample obtained from an individual to be tested; and (b) measuring the presence and/or amount in the test sample of one or more biomarkers selected from the group defined in Table 1(A), Table 1(B), Table 1(C), Table 1(D) and/or Table 1(E) wherein the presence and/or amount in the sample of the one or more biomarker(s) is indicative of an autoimmune disease in the individual. The invention also provides an array and a kit suitable for use in the methods of the invention.

The present invention relates to a method for estimating the effectiveness of treatment with an anti-CD20 agent in a patient with rheumatoid arthritis and who has had an inadequate response to at least one prior biotherapy, consisting in analysing a biological sample of said patient for the expression of a set of biomarkers, the results of which make it possible to determine whether said agent is a treatment that will engender a beneficial response for said patient. The present invention also relates to a system for estimating the effectiveness of said treatment in said patient comprising means for measuring or receiving data, the expression level of said biomarkers and means for processing these data configured to estimate said effectiveness of said treatment in said patient.

The present invention provides an antibody facilitating programmed necrosis of cells. The antibody can cause programmed necrosis of cells in the presence of tumor necrosis factor (TNF). Therefore, an inhibitor for the antibody can be used in the treatment of inflammatory diseases. Further, the present invention provides the application of the antibody facilitating programmed necrosis of cells in the inflammatory disease prognosis.

Disclosed herein are methods for treating subjects having rheumatoid arthritis (RA) with a human anti-interleukin 6 (IL-6) antibody, or antigen-binding portion thereof.

The invention relates to a method of predicting therapeutic responses to TNF blockers before anti-TNF therapy comprising analyzing immune parameters to selected stimuli in patients before therapy and its use for anti-TNF therapy. The invention relates also to a method of determining a predictive biomarker of response to anti-TNF therapy and to the use of the predictive biomarker obtained by the method.