Lupus Foundation of South Jersey: Research

The goals of the Lupus Foundation of South Jersey are to improve the quality of care for Lupus patients and ultimately find a cure. To accomplish those ends we have donated over ($200,000) two hundred thousand dollars to the research team at the University of Pennsylvania.

We currently support many research projects at the University of Pennsylvania. Here’s what they’re working on…
Dr. Caricchio: study of the source of SLE antigens
Dr. Eisenberg: Conducting SLE research, initiated, along with Dr. Albert, Phase I trial of anti-B cell therapy with a new drug (Rituximab). Seeking approval for lupus treatment.
Phase II /III trials of Rituximab to begin in 2005.

Dr. Albert: Database studies & Clinical trials. Construct SLE patient database.
Dr. Cohen: Study of cellular defects in SLE
Dr. Laufer: Study of autoimmunity in mice. Which interactions between T-cells and B-cells mediate the production of autoantibodies?
Dr. Prak: Study of genetic features of antibodies in SLE. Mechanistics studies from man to mouse.

We have recently given an individual grant to Dr. Prak to study the benefits of B-cell depletion therapy. This study provides a critical bridge between an alliance for Lupus research and an NIH study

Brief description of project rationale and aims:
Patients afflicted with systemic lupus erthematosus (SLE) have self-reactive (autoreactive) white blood cells called B-cells that make antibodies and contribute to disease. Clinical trials using B-cell depleting agents are underway and early results from several trials are encouraging, further supporting a central role for B-cells in SLE. Previous experience in a phase I, open trial of SLE patients who received depletion therapy with rituximab (anti-CD20) has shown that while most patients exhibited clinical improvement, the response to therapy varied substantially. It is believed that the patients who responded best to B-cell depletion therapy are those who 1. re-set their B-cell repertoire as a result of B cell depletion and 2. have functional central B-cell tolerance mechanisms. Re-setting the B lymphocyte repertoire may afford an SLE patient a time of reduced disease activity, until autoimmune B-cells return. However, if central B-cell tolerance is dysfunctional (meaning that autoreactive B-cells are produced in the bone marrow and allowed to escape and wander uncensored through the rest of the body), then the disease-causing B-cells may rapidly return, even if the circulating B-cell repertoire is re-set. This study is to determine which SLE patients are most likely to benefit from B-cell depletion therapy.

In the short term, we hope that these studies will result in improved definitions of peripheral B-cell subsets and insights into their dynamics of reconstruction. In the long term, we hope that these studies will help define new biomarkers, such as the B-cell phenotype at baseline and the level of receptor editing, which may be used to predict and monitor the efficacy or B-cell depletion therapy in patients with SLE.