The goals ofthe Clinical Core are to provide a uniform approach to subject recruitment and charactehzation, and to provide clinical samples forthe individual projects.
Aim 1. Clinical and human subjects support for individual projects Task 1. We shall prepare and maintain protocols and consents interfacing with the IRB, maintaining and stohng records, creating and filling out the clinical research forms, creating and maintaining a manual of operation for handling and disthbuting samples, and assunng training of study personnel who have direct patient contact. Task 2. We shall recruit a sufficient number of patients and healthy volunteers for the proposed immunological studies. Task 3. We shall clinically evaluate all patients and determination of disease activity. Clinical assessors will be kept blinded to investigative laboratory studies until all experimental data has been entered into the webbased data management system. Task 4. We shall coordinate specimen handling and the disthbution of samples to laboratory investigators. Laboratory investigators will be kept blind to subject group until all experimental data has been entered into the web-based data management system. Task 5. We shall draw penpheral blood specimens and coordinate all other procedures including bone marrow and synovial biopsies. Task 6. We will evaluate a interferon signature, biological activity of type 1 interferon, IFN regulated chemokines, and levels of BLyS and APRIL, Aim 2. In vivo labeling In cooperation with the GCRC deutehum-labeled glucose will be used for the in vivo labeling and collect penpheral blood specimens for ex vivo analysis of lymphocyte subsets. Individual projects will then isolate lymphocytes subsets of interest. A subcontract with the University of California at Berkley will measure incorporation of deuterium into lymphocyte subsets using mass spectroscopy.
B cell targeted therapies are now being tested to treat a vanety of autoimmune diseases and one B cell targeted therapy, htuximab, has already been approved for the treatment of rheumatoid arthntis, and has shown promise for multiple sclerosis, vasculitis, and childhood diabetes mellitus. This program project will markedly enhance our understanding of B cells in health and in disease and improve our understanding of how and why B cell targeted therapies work in some patients and in some diseases and not in others.
|Meednu, Nida; Zhang, Hengwei; Owen, Teresa et al. (2016) Production of RANKL by Memory B Cells: A Link Between B Cells and Bone Erosion in Rheumatoid Arthritis. Arthritis Rheumatol 68:805-16|
|Rahimi, Homaira; Bell, Richard; Bouta, Echoe M et al. (2016) Lymphatic imaging to assess rheumatoid flare: mechanistic insights and biomarker potential. Arthritis Res Ther 18:194|
|Kuzin, Igor I; Kates, Stephen L; Ju, Yawen et al. (2016) Increased numbers of CD23(+) CD21(hi) Bin-like B cells in human reactive and rheumatoid arthritis lymph nodes. Eur J Immunol 46:1752-7|
|Newell, K A; Asare, A; Sanz, I et al. (2015) Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. Am J Transplant 15:2908-20|
|Adlowitz, Diana G; Barnard, Jennifer; Biear, Jamie N et al. (2015) Expansion of Activated Peripheral Blood Memory B Cells in Rheumatoid Arthritis, Impact of B Cell Depletion Therapy, and Biomarkers of Response. PLoS One 10:e0128269|
|Bird, Anna K; Meednu, Nida; Anolik, Jennifer H (2015) New insights into B cell biology in systemic lupus erythematosus and SjÃ¶gren's syndrome. Curr Opin Rheumatol 27:461-7|
|Wilmore, Joel R; Asito, Amolo S; Wei, Chungwen et al. (2015) AID expression in peripheral blood of children living in a malaria holoendemic region is associated with changes in B cell subsets and Epstein-Barr virus. Int J Cancer 136:1371-80|
|Halliley, Jessica L; Tipton, Christopher M; Liesveld, Jane et al. (2015) Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow. Immunity 43:132-45|
|Bouta, Echoe M; Li, Jie; Ju, Yawen et al. (2015) The role of the lymphatic system in inflammatory-erosive arthritis. Semin Cell Dev Biol 38:90-7|
|Wei, Chungwen; Jenks, Scott; Sanz, IÃ±aki (2015) Polychromatic flow cytometry in evaluating rheumatic disease patients. Arthritis Res Ther 17:46|
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