Provided are a vesicle and the use thereof. The vesicle is an induced vesicle, and the sources thereof include stem cells or somatic cells, and the possessed markers include Syntaxin 4. Compared with an exosome in mesenchymal stem cells, the vesicle can specifically express Syntaxin 4 and can be used to distinguish characteristic markers of MSC-derived vesicles and exosomes. The vesicle can play a procoagulant effect in vitro, can improve the bleeding tendency of mice with hemophilia after in vivo injection, and can be used for the treatment of improving the bleeding tendency of hemophilia. In addition, the vesicle can be expelled through the skin and hair.

The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.

Methods of assessing or monitoring the effect, efficacy, responsiveness to treatment, and/or determining a dose or dosing regimen of therapeutic agents, such as integrin beta7 antagonists, for the treatment of gastrointestinal inflammatory disorders are provided. In certain aspects, methods of using integrin beta7 subunit-containing receptor occupancy by the integrin beta7 antagonist on colonic lymphocytes as an indicator (“biomarker”) of the effect, efficacy, or responsiveness to treatment, and/or as a means to determine dosing or dosing regimens of therapeutic agents such as beta7 integrin antagonists for the treatment of gastrointestinal inflammatory disorders are provided. In certain aspects, methods of assessing the effect, efficacy, or responsiveness to beta7 integrin antagonist treatment by measuring gene expression levels of one or more integrin receptor ligands, lymphocyte genes, cytokine genes, or the number of alphaE-positive cells in intestinal crypt epithelium are provided.

The present invention is directed to methods of using biomarkers to assess treatment of gastrointestinal inflammatory disorders with beta7 antagonists. More particularly, the present invention relates to methods of using the level of gut-homing lymphocytes in peripheral blood, the level of drug occupancy on gut-homing lymphocytes, and/or the level of beta7 integrin receptors on gut-homing lymphocytes as indicators (or biomarkers) of the effect, efficacy, safety, prognosis, and/or dosing of therapeutic agents, such as beta7 integrin antagonists, for the treatment of gastrointestinal inflammatory disorders.

Provided are methods and compositions for treating kidney disease, such as chronic kidney disease (CKD), in which the methods and compositions comprise antibodies or an antigen binding fragment thereof that specifically and selectively bind to human αvβ8 integrin, which was discovered, as described, to be highly expressed on kidney cells and tissue, and, in particular, diseased or fibrotic kidney tissue. The disclosed anti-αvβ8 integrin antibodies bind to human αvβ8 integrin in the kidney and block the activation of TGF-β from its latent form in kidney tissue. The anti-αvβ8 antibodies in the disclosed methods reduce, attenuate, or abrogate kidney fibrosis, which is associated with the activities of αvβ8 integrin and TGF-β in kidney tissue. The disclosed antibodies and methods effectively treat kidney disease, in particular, fibrosis associated with kidney disease, such as CKD, in individuals in need thereof.

The invention relates to methods and products for the identification of a clinically significant immune response in subjects treated with a therapeutic protein. Aspects of the invention relate to methods and compositions for identifying a clinically significant immune response in patients treated with therapeutic amounts of a VLA4 binding antibody (e.g., natalizumab).

The present invention relates to αvβ8 antagonists, anti-αvβ8 antibodies or immunoconjugates for reducing TGFβ activation in an individual. Further provided are compositions comprising one of the αvβ8 antagonists, anti-αvβ8 antibodies or immunoconjugates, methods for using the compositions, and related subject matter.

Methods and assays for detecting natalizumab in a sample, natalizumab-peptide complexes in a sample, and point-of-care devices for detecting natalizumab in a sample are described herein.

The present invention in various aspects and embodiments involves pharmaceutical compositions prepared by contacting a candidate α- or β-integrin-binding molecule, or panel thereof, with an integrin heterodimer, and quantifying heterodimer disruption by the candidate molecule. An integrin-binding molecule, or derivative thereof, that disrupts the integrin heterodimer is selected and is formulated into a pharmaceutical composition for administration to a subject, e.g., who has a disease or disorder related to abnormal vascularization.

A method for treating a human patient suffering from fistulizing Crohn's disease, comprising administering to a patient suffering from fistulizing Crohn's disease, a humanized antibody having binding specificity for human α4β7 integrin, wherein the human patient has a seton that was surgically placed prior to administration of the antibody, and wherein the dosing regimen induces fistula(e) healing.