Abstract: Described herein are compositions and methods for engineering Treg cells for treatment of diabetes. The engineered Treg cells provided herein may be dual-edited (i.e., edited in two different loci in the cell genome), a first locus being the FOXP3 locus and the second locus being the TRAC locus. The engineering of dual-edited Treg cells as provided here may include selective expansion of dual-edited cells using a ligand that initiates and/or maintains IL-2 signal transduction in dual-edited cells. The engineering of dual-edited Treg cells as provided here may stably express FoxP3 and an exogenous TCR.

Abstract: Some embodiments of the methods and compositions provided herein relate to efficient editing of more than one genetic locus in a cell using a chemical-inducible signaling complex (CISC) system. Some embodiments include use of such systems to edit a FOXP3 locus gene and TRAC locus in a Treg cell. More embodiments herein relate to use of gene-edited Treg cells to suppress activation and/or proliferation of certain populations of cells.

Abstract: Compositions and methods for detection of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients. Patient samples known or suspected of containing ACPAs were probed against citrullinated proteins, and antibody responses to 190 citrullinated proteins in 20 RA patients were investigated. Unique antibody reactivity patterns in both clinical anti-cyclic citrullinated peptide assay positive (CCP+) and negative (CCP?) RA patients were observed. At individual antigen levels, six novel antibody/antigen complexes were discovered and validated against specific citrullinated antigens (Myelin Basic Protein (MBP), osteopontin (SPP1), flap endonuclease (FEN1), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGF1) and stanniocalcin-2 (STC2)) in RA patients. Identification of immune-dominant epitope(s) for citrullinated MBP was also performed. The identified biomarkers have high specificity, especially MBP.

Abstract: Compositions and methods for detection of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients. Patient samples known or suspected of containing ACPAs were probed against citrullinated proteins, and antibody responses to 190 citrullinated proteins in 20 RA patients were investigated. Unique antibody reactivity patterns in both clinical anti-cyclic citrullinated peptide assay positive (CCP+) and negative (CCP?) RA patients were observed. At individual antigen levels, six novel antibody/antigen complexes were discovered and validated against specific citrullinated antigens (Myelin Basic Protein (MBP), osteopontin (SPP1), flap endonuclease (FENI), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGF1) and stanniocalcin-2 (STC2)) in RA patients. Identification of immune-dominant epitope(s) for citrullinated MBP was also performed. The identified biomarkers have high specificity, especially MBP.

Abstract: Compositions and methods are disclosed that relate to the discovery of citrullinated oligopeptides of 9-14 amino acids or 9-18 amino acids, comprising peptide sequences derived from the polypeptide sequence of human tenascin-C (TNC) containing citrullination-dependent immunological epitopes that, remarkably, are antigen-specifically recognized by both autoantibodies and CD4+ T cells from human subjects having rheumatoid arthritis (RA). The citrullinated TNC (citTNC) oligopeptides are useful for isolating autoantibodies from, and detecting autoantibodies in, biological fluids from subjects having or suspected of having RA. Also described are uses of citTNC oligopeptides to prepare compositions for induction of citTNC autoantigen-specific immunological tolerance, including tolerogens and citTNC-specific Treg cells.

Abstract: Some embodiments of the compositions and methods disclosed herein include gene-edited, artificial immunoregulatory T cells (airT cells) comprising a constitutively expressed FoxP3 gene product expressed at a level equal to or greater than the level of FoxP3 expression in natural T regulatory (Treg or suppressor T) cells, and a transduced (e.g., artificially engineered by gene editing, viral vector transduction, transfection or other genetic engineering methodologies) T cell receptor (TCR). In some embodiments, the TCR is preferably specific for an antigen associated with an autoimmune, allergic, or other inflammatory condition. Some embodiments include methods for the preparation and/or use of airT cells. Some such embodiments include use of airT cells for the treatment and/or amelioration of a disorder, in which antigen-specific immunosuppression may be beneficial, such as an autoimmune, allergic, or other inflammatory disorder.

Abstract: Compositions and methods for detection of anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) patients. Patient samples known or suspected of containing ACPAs were probed against citrullinated proteins, and antibody responses to 190 citrullinated proteins in 20 RA patients were investigated. Unique antibody reactivity patterns in both clinical anti-cyclic citrullinated peptide assay positive (CCP+) and negative (CCP?) RA patients were observed. At individual antigen levels, six novel antibody/antigen complexes were discovered and validated against specific citrullinated antigens (Myelin Basic Protein (MBP), osteopontin (SPP1), flap endonuclease (FEN1), insulin like growth factor binding protein 6 (IGFBP6), insulin like growth factor I (IGF1) and stanniocalcin-2 (STC2)) in RA patients. Identification of immune-dominant epitope(s) for citrullinated MBP was also performed. The identified biomarkers have high specificity, especially MBP.

Abstract: The present invention provides methods for generating mammalian T cell populations comprising antigen-specific CD4+CD25+ regulatory T cells from freshly isolated CD4+CD25? T cells. The method comprises selecting CD4+CD25? T cells from a sample obtained from a mammalian subject; determining the MHC Class II type of the subject; inducing the generation of antigen-specific regulatory T cells by contacting the isolated CD4+CD25? T cells in a culture vessel with an induction agent for a time period sufficient to generate antigen-specific CD4+CD25+ regulatory T cells; and selecting the CD4+CD25+ antigen-specific regulatory T cells by sorting the cells in the induction culture with a selection agent comprising at least one artificial multimeric MHC Class II/peptide complex that corresponds to the MHC Class II type of the subject.