New York Society for the Ruptured and Crippled Maintaining the Hospital for Special Surgery

New York Society for the Relief of the Ruptured and Crippled,

New York Society for the Ruptured and Crippled Maintaining the Hospital

New York Society for the Relief of the Ruptured and Crippled Maintaining

New York Society for the Ruptured and Crippled Maintaing the Hospital

New York Society for the Ruptured and Crippled Maintaining the Hopital for Special Surgery

Mary K Crow

Steven M Friedman

Yixin Li

Guang-Rong Sun

Joseph R Tumang

David Posnett

Mikhail Olferiev

Radha Krishna Vakkalanka

This invention related to methods and assays for screening for, identifying, and predicting the severity and clinical manifestations of systemic lupus erythematosus (SLE). Specifically, this invention provides various biomarkers for the prediction of flares of the disease both in number and severity, as well as clinical manifestations of the disease, and methods of using these biomarkers to correctly subclassify patients with this disease, and prescribe appropriate treatment. The invention also provides for biomarkers of lupus disease activity, i.e., flares, as well as biomarkers for the prediction of future flares, and methods of using these biomarkers. The invention also provides, in these biomarkers, targets and methods for drug development and basic research for SLE.

Biomarkers for disease activity and clinical manifestations systemic lupus erythematosus

Four unique transcripts have been isolated from the &bgr; chain of the T cell receptor in T cells in the synovial tissue of a patient with rheumatoid arthritis. Two of these transcripts were isolated from fresh synovial tissue and two were isolated from a T cell line derived from the synovial tissue. The sequences of the four transcripts are highly homologous, with a conserved amino acid sequence of IGQ_N in the highly diverse V-D junction. The &agr; chain and the antigenic specificity of the T cell line derived transcripts has also been characterized.

Conserved T-cell receptor sequences

The present invention provides diagnostic methods for determining the severity of disease or disease activity in patients suffering from autoimmune, inflammatory, malignant, vascular, or viral diseases, which involves measuring the level of CD40 ligand (CD40L) in the patient's serum or other body fluid.

Methods of determining disease activity in SLE patients by correlating

Four unique transcripts have been isolated from the .beta. chain of the T cell receptor in T cells in the synovial tissue of a patient with rheumatoid arthritis. Two of these transcripts were isolated from fresh synovial tissue and two were isolated from a T cell line derived from the synovial tissue. The sequences of the four transcripts are highly homologous, with a conserved amino acid sequence of IGQ.sub.-- N in the highly diverse V-D junction. The .alpha. chain and the antigenic specificity of the T cell line derived transcripts has also been characterized.

DNA encoding conserved T-cell receptor sequences

Antibodies to specific subsets of T cells can be obtained by incubating a polyclonal population of T cells with a microbial superantigen, and injecting of the incubated T cells into a host animal. Antibodies obtained by this method and methods of use thereof are also provided.

Method of producing antibodies to a restricted population of T

This invention relates to a method of obtaining antibodies specific to a population of T-lymphocytes (T cells) restricted by V.beta. gene usage. The invention also relates to the antibodies obtained and to methods of using them. According to the invention, T cells are incubated with an effective amount of a superantigen under conditions and for a time sufficient to allow division and growth of T-cells reactive to the superantigen. The incubated T-cells are injected into a mammal, and thereafter serum containing antibodies specific to the incubated and injected T-cells is removed from the mammal.

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New York, NY, United States of America

Mary K Crow