Oklahoma Medical Research Foundation

Other

The University of Oklahoma

Judith Ann James

John B Harley

Kenneth M Kaufman

Melissa E Munroe

R Hal Scofield

Sherry Crowe

Darise Farris

Melissa Elizabeth Munroe

The present invention includes methods, systems, and kits, for identifying and modifying the treatment of a systemic lupus erythematosus (SLE) patient prior to the presence of autoantibodies, comprising: (a) obtaining a dataset representing protein expression level values for cytokines and molecules; (b) assessing the dataset for protein expression levels of at least one innate serum mediator; (c) assessing the dataset for protein expression levels of at least one adaptive serum mediator; and (d) determining the likelihood that the patient will develop SLE prior to the onset of autoantibodies when compared to a control.

Biomarkers for assessing risk of transitioning to systemic lupus erythematosus classification and disease pathogenesis

The present invention involves the identification of biomarkers that are predictive of impeding systemic lupus erythematosus (SLE) disease flare. Methods for treating patients so identified are also provided.

Biomarkers for systemic lupus erythematosus disease activity, and intensity and flare

Data consistent with autoimmune disease being caused by Epstein-Barr virus are shown. Based on this evidence, an effective vaccine would prevent the autoimmune disease in those vaccinated, modified or administered so that the vaccine is not itself capable of inducing autoimmune disease. In the case of anti-Sm, structures to be avoided in an Epstein-Barr virus-derived vaccine have been identified. Differences have been identified in the immune responses to Epstein-Barr infection between individuals who develop a specific autoimmune disease and those who do not. These differences are used to distinguish those who are at greater risk for developing specific autoimmune diseases from those who are a lesser risk. Assuming Epstein-Barr virus causes autoimmune disease and that Epstein-Barr virus remains latent in the patient for life, reactivation of the virus from the latent state is important in generating or maintaining the autoimmune response that culminates in autoimmune disease. Cells infected with latent virus may also encourage autoimmunity. Based on the understanding that reactivation or latency are important to produce or sustain autoimmunity, then therapies directed against Epstein-Barr virus will also be effective therapies for the autoimmune manifestations of disease for which Epstein-Barr virus is responsible.

Diagnostics and therapy of epstein-barr virus in autoimmune disorders

Compositions and methods effective for eliciting an immune response for preventing or reducing infection or improving clinical outcomes caused byare provided. The compositions include a naturally occurring or synthetic protein, peptide, or protein fragment containing all or an active portion of an antigenic epitope associated with anthrax toxin proteins optionally combined with a pharmaceutically acceptable carrier. The preferred antigenic epitopes correspond to immunogenic regions of protective antigen, lethal factor or edema factor, either individually or in combination. In addition, methods and compositions containing antibodies for reducing the effects of anthrax toxins are described. The methods involve administering to a human or animal the compositions described herein in a dosage sufficient to elicit an immune response or treat the anthrax infection.

Anthrax compositions and methods of use and production

Compositions that bind viral proteins that are specifically expressed during the latent stage of the viral life cycle are disclosed. These compositions bind the latent viral proteins while the viral proteins are expressed in their cellular host, and provide a means for targeting cells that harbor latent virus. In a preferred embodiment the compositions are antibodies which bind the extracellular region of the latent viral protein, most preferably LMP-2A, an EBV latent protein, which are conjugated to a diagnostic or cytotoxic agent or immobilized to a solid support for removal of the infected cells. These antibodies are capable of distinguishing cells expressing EBV DNA from cells which are not expressing EBV DNA. Compositions that can be used to elicit production of these antibodies, or as a vaccine, are also disclosed. Methods for generating diagnostic or cytotoxic reagents and vaccines based on the viral epitopes that identify cells harboring latent virus are also disclosed. The antibody conjugates can be used in diagnostic assays to identify cells expressing latent viral protein and people who are harboring latent viral particles. The antibody conjugates can also be used to remove the infected cells or to kill the infected the cells. Alternatively, or in addition, the viral proteins or portions thereof can be used as a vaccine to induce an immune reaction by the host to kill the infected cells. These methods can be used to detect or treat patients harboring latent viruses like EBV and who are at risk of developing a disease such as an autoimmune disease like systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Assays and therapies for latent viral infection

A number of octapeptides were generated from the sequences encoding the 60 kDa Ro/SSA peptide, the La/SSB autoantigen, the 70 kD nuclear ribonucleoprotein (nRNP), and the Sm B/B' polypeptide, which represent linear epitopes for autoantibodies present in the sera of SLE and SS patients. These peptides are useful in solid phase assays for patients characterized by the presence of these autoantibodies, and can be used to categorize patients as to the likelihood of developing certain conditions associated with SLE. The peptides are also potentially useful in treatment of these patients using immobilized peptide to remove autoantibody and to block binding of the autoantibodies with patient molecules reactive with the autoantibodies.

Methods and reagents for diagnosis of autoantibodies

Diagnostics and therapy of Epstein-Barr virus in autoimmune disorders

Compositions that bind specific viral proteins expressed during the latent stage of the viral life cycle are disclosed. These compositions bind the latent viral proteins while the viral proteins are expressed in their cellular host, and provide a means for targeting cells that harbor latent virus. In a preferred embodiment the compositions are antibodies which bind the extracellular region of the latent viral protein, most preferably LMP- A, an EBV latent protein, conjugated to a diagnostic or cytotoxic agent or immobilized to a solid support for infected cell removal. These antibodies can distinguish cells expressing EBV DNA from cells which do not. Compositions that can be used to elicit production of these antibodies, or as a vaccine, are also disclosed. Methods for generating diagnostic or cytotoxic reagents and vaccines based on the viral epitopes that identify cells harboring latent virus are also discloset. The antibody conjugates can be used in diagnostic assays to identify cells expressing latent viral protein and people harboring latent viral particles. The antibody conjugates can also be used to remove infected cells or kill the infected cells. Alternatively, or in addition, the viral proteins or portions thereof can be used as a vaccine to induce an immune reaction by the host to kill the infected cells. These methods can be used to detect or treat patients harboring latent viruses like EBV and who risk developing autoimmune diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

A specific method has been developed to produce an autoimmune response and resulting clinical symptoms for a particular disease process. Peptides or other structures derived from an autoantigen and which are bound by auto antibody or T cell receptors are identified and used to induce an immune response. This immune response evolves into an autoimmune response directed against the other portions of the protein from which the peptide was derived. Subsequently, clinical manifestations may appear that are also found in the clinical illness. selected from the group including viruses, bacteria, fungi, parasites, rickettsia, plasmids, and insects which contains a structure or a peptide sequence that is similar to a structure or peptide sequence that has been identified by the method of claim,to the extent that it is bound by one of the group selected from antigen specific B cell surface receptors, and antigen specific T cell receptors.

Growing community of inventors

Edmond, OK, United States of America

Judith Ann James