Regulatory T Cells in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a potentially life-threatening multisystem autoimmune disorder with a female to male ration of 9:1, affecting approximately one in 1000 women of childbearing age. It is characterized by the production of a myriad of autoantibodies. SLE may affect every organ of the body leading to serious disability, pain and disfiguring skin lesions. Treatment regimes are complex, expensive and have many side effects. A critical question in our understanding and aim of this project is how immunological self-tolerance is overcome in lupus patients allowing the emergence of autoantibodies and autoreactive lymphocytes which attack the body and cause organ damage. In addition to central thymus-mediated tolerance, a second line of self-defence, "peripheral" immune tolerance, exists which prohibits the expansion of autoreactive cells upon contact with self antigen in the periphery. The origin, regulation and phenotype of these regulatory cells of the immune system is however largely unknown. We hypothesize that in SLE these cells are deficient. As approved by ethics committee we will analyse blood samples from paediatric and adult lupus patients by following methods: flow cytometry, EPIMAX (a novel LUMINEX based technology) to characterize cell proliferation and cytokine production, microarray analysis, PCR and ELISA of regulatory HLA-G molecules, and finally cell culture experiments. We hope to thereby understand better the pathogenesis of SLE and identify new diagnostic and therapeutic targets urgently needed in clinical application.