Systemic Lupus Erythematosus: A.Studies on an ldiotype Specific Dendritic Cell Vaccine. B.Association of Lupus Calcinosis with Calcifying Nanoparticles.

Summary: Systemic lupus erythrematosus (SLE) is an autoimmune disease characterized by the production of anti-DNA antibodies. The primary goal of this study was to activate T cells with specificity toward lupus B cells presenting anti-DNA antibody idiotopes on their surface. Monocyte derived dendritic cells were obtained from peripheral blood of healthy donors and lupus patients. Affinity purified anti-DNA antibodies were obtained from lupus patients' plasmas. The efficacy of different carrier proteins, conjugated to lgG, was evaluated, and KLH found to be the most efficient for antigen uptake. The cognate dendritic cells were evaluated for their capacity to activate autologous T cells, and generate a Th1 mediated response which was evaluated by proliferation assays and interferony secretion. During the vaccine study a patient presented with panniculitis, CREST syndrome and a calcinotic exudate. A secondary goal of my study was to analyze this exudate. Calcifying nanoparticles were isolated in lymphocyte culture medium. They were characterized by Von Kassa staining for hydroxyapatite, solubilization by the calcium chelating agent EDT A, and light and scanning electron microscopy. A novel method was developed, using a specific monoclonal antibody, to analyze the calcifying nanoparticles. This method allowed for an approximate quantification of the particles. These particles increased in numbers when incubated for different time periods, and their numbers were decreased when incubated in the presence of minocyclin. Concomitantly, the panniculi in the patient underwent remission with long term antibiotic therapy. CNPs were also obtained from fetal bovine serum and human plasma samples from both lupus patients and healthy donors. Peripheral blood mononuclear cells from healthy donors and lupus patients were analyzed in vitro for their reactivity when incubated in the presence of a biofilm, generated by the calcifying nanoparticles. Viability, proliferation, and co-stimu
2007
Includes bibliography.
Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2007.
Collection: FAU Electronic Theses and Dissertations Collection
Charles E. Schmidt College of Science