Detection and treatment of autoimmune disorders

Abstract

Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.

1 . A method of detecting the presence or absence of an autoimmune disease in a patient comprising:
 identifying a patient that is suspected of having or is at risk of having an autoimmune disease;   obtaining a biological sample from said patient;   determining the level of PD-L1 or antibody specific for PD-L1 in said biological sample; and   correlating the level of PD-L1 or antibody specific for PD-L1 in said biological sample with the presence or absence of an autoimmune disease.   
     
     
         2 . The method of  claim 1 , wherein the autoimmune disease is selected from the group consisting of multiple sclerosis, Crohn's disease, SLE, Alzheimer's disease, rheumatoid arthritis, psoriatic arthritis, enterogenic spondyloarthropathics, insulin dependent diabetes mellitus, autoimmune hepatitis, thyroiditis, transplant rejection and celiac disease. 
     
     
         3 . The method of  claim 1 , wherein the autoimmune disease is SLE. 
     
     
         4 . The method of  claim 1 , wherein the autoimmune disease is rheumatoid arthritis. 
     
     
         5 . The method of  claim 1 , wherein the biological sample comprises at least one of cells, cell extracts, peripheral blood lymphocytes, serum, plasma and biopsy specimens. 
     
     
         6 . The method of  claim 1 , further comprising providing an antibody that is specific for PD-L1. 
     
     
         7 . The method of  claim 6 , further comprising providing an antibody specific for a to cell surface marker on a monocyte or dendritic cell. 
     
     
         8 . The method of  claim 6 , wherein the antibody is fluorescently-labeled. 
     
     
         9 . The method of  claim 1 , wherein the determining step employs flow cytometry. 
     
     
         10 . A method of distinguishing between the presence of SLE or a bacterial or viral infection in a patient comprising:
 identifying a patient that is suspected of having or is at risk of having an SLE, a bacterial, or viral infection;   obtaining a biological sample from said patient;   determining the level of PD-L1 or antibody specific for PD-L1 in said biological sample; and   correlating the presence, absence, or amount of PD-L1 or antibody specific for PD-L1 in said biological sample with the presence or absence of SLE or a bacterial or viral infection.   
     
     
         11 . The method of  claim 10 , wherein the biological sample at least one of cells, cell extracts, peripheral blood lymphocytes, serum, plasma and biopsy specimens. 
     
     
         12 . The method of  claim 10 , further comprising providing an antibody that is specific for PD-L1. 
     
     
         13 . The method of  claim 12 , further comprising providing an antibody specific for a to cell surface marker on a monocyte or dendritic cell. 
     
     
         14 . A method of distinguishing between an active autoimmune disease and an autoimmune disease in remission in a patient comprising the steps of:
 identifying a patient that is suspected of having an active autoimmune disease or an autoimmune disease in remission;   obtaining a biological sample from said patient;   determining the level of PD-L1 or antibody specific for PD-L1 in said biological sample; and   correlating the presence, absence, or amount of PD-L1 or antibody specific for PD-L1 in said biological sample with the presence of an active autoimmune disease or an autoimmune disease in remission.   
     
     
         15 . The method of  claim 14 , wherein the autoimmune disease is at least one selected from the group consisting of multiple sclerosis, Crohn's disease, SLE, Alzheimer's disease, rheumatoid arthritis, psoriatic arthritis, enterogenic spondyloarthropathies, insulin dependent diabetes mellitus, autoimmune hepatitis, thyroiditis, transplant rejection and celiac disease. 
     
     
         16 . The method of  claim 14 , wherein the autoimmune disease is SLE. 
     
     
         17 . The method of  claim 14 , wherein the autoimmune disease is rheumatoid arthritis. 
     
     
         18 . The method of  claim 14 , wherein the biological sample comprises at least one of cells, cell extracts, peripheral blood lymphocytes, serum, plasma and biopsy specimens. 
     
     
         19 . The method of  claim 14 , further comprising providing an antibody that is specific for PD-L1. 
     
     
         20 . The method of  claim 19 , further comprising providing an antibody specific for a cell surface marker on a monocyte or dendritic cell. 
     
     
         21 . A kit for detecting the presence of an autoimmune disease comprising:
 an antibody specific for PD-L1; and   a correlation of the amount of bound antibody specific for PD-L1 or antibody specific for PD-L1 in a biological sample with the presence or absence of said autoimmune disease.   
     
     
         22 . The kit of  claim 21 , wherein the autoimmune disease is SLE. 
     
     
         23 . The kit of  claim 21 , wherein the autoimmune disease is rheumatoid arthritis. 
     
     
         24 . A method of treating or preventing an autoimmune disease or treating or preventing the symptoms of an autoimmune disease comprising the steps of:
 identifying a patient in need of such treatment; and   administering to the patient at least one caspase inhibitor in an amount sufficient to induce or increase PD-L1 expression by the cells of the patient,   thereby treating or preventing the autoimmune disease or treating or preventing the symptoms of the autoimmune disease.   
     
     
         25 . The method of  claim 24 , wherein the at least one caspase inhibitor comprises a poly-caspase inhibitor. 
     
     
         26 . The method of  claim 24 , wherein the at least one caspase inhibitor comprises at least one of Z-WEHD-fmk, Z-VDVAD-fmk, Z-DEVD-fmk, Z-YVAD-fmk, Z-VE1D-fmk, Z-IETD-fmk Z-LEHD-fmk, Z-AEVD-fmk, Z-LEED-fmk, Z-VAD-fmk and OPH. 
     
     
         27 . The method of  claim 24 , wherein the-caspase inhibitor is OPH. 
     
     
         28 . The method of  claim 24 , wherein the autoimmune disease is SLE. 
     
     
         29 . The method of  claim 24 , wherein the autoimmune disease is rheumatoid arthritis. 
     
     
         30 . The method of  claim 24 , wherein the administering of the caspase inhibitor to the patient comprises at least one of intravenous, intraperitoneal, inhalation, intramuscular, subcutaneous, nasal and oral administration. 
     
     
         31 . The method of  claim 24 , further comprising the administration of at lease one selected from therapeutics targeting HLA molecules, CD18, CD2, CD4, CD28, Fc-gamma 3 receptor, Fc gamma receptor 2a, CTLA4, or TGF-b in an amount sufficient to induce or increase PD-L1 expression by the cells of the patient. 
     
     
         32 . A method of treating or preventing an autoimmune disease or treating or preventing the symptoms of an autoimmune disease comprising the steps of:
 identifying a patient in need of such treatment;   removing a biological sample from the patient;   exposing the biological sample to at least one caspase inhibitor ex vivo in an amount sufficient to induce or increase the expression of PD-L1 on the cells in the biological sample;   washing the cells; and   administering the cells to the patient thereby treating or preventing the autoimmune disease or treating or preventing the symptoms of the autoimmune disease.   
     
     
         33 . The method of  claim 32 , wherein the at least one caspase inhibitor comprises a poly-caspase inhibitor. 
     
     
         34 . The method of  claim 32 , wherein the biological sample comprises at least one of cells, cell extracts, peripheral blood lymphocytes, serum, plasma and biopsy specimens. 
     
     
         35 . The method of  claim 32 , wherein the at least one caspase inhibitor comprises at least one of Z-WEHD-fmk, Z-VDVAD-fmk, Z-DEVD-fmk, Z-YVAD-fmk, Z-VEID-fmk, Z-IETD-fmk Z-LEHD-fmk, Z-AEVD-fmk, Z-LEED-fmk, Z-VAD-fmk and OPH. 
     
     
         36 . The method of  claim 32 , wherein the-caspase inhibitor is OPH. 
     
     
         37 . The method of  claim 32 , wherein the autoimmune disease is SLE. 
     
     
         38 . The method of  claim 32 , wherein the autoimmune disease is rheumatoid arthritis. 
     
     
         39 . The method of  claim 32 , further comprising the step of exposing biological sample to at least one selected from therapeutics targeting HLA molecules, CD18, CD2, CD4, CD28, Fc-gamma 3 receptor, Fc gamma receptor 2a, CTLA4, or TGF-b in an amount sufficient to induce or increase PD-L1 expression by the cells of the patient.