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.
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|León, Beatriz; Ballesteros-Tato, André; Randall, Troy D et al. (2014) Prolonged antigen presentation by immune complex-binding dendritic cells programs the proliferative capacity of memory CD8 T cells. J Exp Med 211:1637-55|
|Sanz, Iñaki (2014) Rationale for B cell targeting in SLE. Semin Immunopathol 36:365-75|
|Wang, Wensheng; Rangel-Moreno, Javier; Owen, Teresa et al. (2014) Long-term B cell depletion in murine lupus eliminates autoantibody-secreting cells and is associated with alterations in the kidney plasma cell niche. J Immunol 192:3011-20|
|Palanichamy, Arumugam; Bauer, Jason W; Yalavarthi, Srilakshmi et al. (2014) Neutrophil-mediated IFN activation in the bone marrow alters B cell development in human and murine systemic lupus erythematosus. J Immunol 192:906-18|
|Finak, Greg; Jiang, Wenxin; Krouse, Kevin et al. (2014) High-throughput flow cytometry data normalization for clinical trials. Cytometry A 85:277-86|
|Bouta, Echoe M; Wood, Ronald W; Brown, Edward B et al. (2014) In vivo quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice. J Physiol 592:1213-23|
|León, Beatriz; Bradley, John E; Lund, Frances E et al. (2014) FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability. Nat Commun 5:3495|
|Zhang, Hengwei; Hilton, Matthew J; Anolik, Jennifer H et al. (2014) NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF-?B. J Clin Invest 124:3200-14|
|Roberts, Mustimbo E P; Kaminski, Denise; Jenks, Scott A et al. (2014) Primary Sjögren's syndrome is characterized by distinct phenotypic and transcriptional profiles of IgD+ unswitched memory B cells. Arthritis Rheumatol 66:2558-69|
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