? Monoclonal Antibody and Reagent Core This Program Project addresses the impact of antibodies cross-reactive to DNA and the N-methyl D-aspartate receptor (NMDAR), DNRAbs, on adult and fetal brain. The premise of the program is that DNRAbs induce a chronic inflammatory state in the adult brain and permanent cognitive impairment in offspring exposed to these antibodies in vitro Projects 1 and 3 both utilize a panel of monoclonal DNRAbs. These need to be produced in large quantity. The Monoclonal Antibody and Reagent Core will produce both human and murine antibodies and will test these for preservation of antigen binding. The Core will produce antibody that is validated for binding to DNA, DWEYS and the extracellular domains of GluN2A/B. The Core will generate GluN2A/B extracellular domains for use in ELISAs to confirm antibody specificity. Projects 2 and 3 requires that serum be tested for DNRAb titer. The Core will provide quality control for these assays also. Project 3 will need large amounts of decoy antigen of high purity to be produced. This facility will be cost-effective and will maintain quality control for all 3 projects in the Program. This represents an efficient approach to the generation of reagents to be used by multiple investigators and one that maximizes the production of high quality reagents. Antibodies represent a highly versatile tool in medical research. They are used in diagnostics, in basic and clinical research and in developing new therapies. The DNRAbs created in our laboratory are utilized in all of the above areas not only in our studies but in many laboratories within the United States and abroad.

Public Health Relevance

? Monoclonal Antibody and Reagent Core This Core will provide monoclonal antibodies and assessments of antibody titer for the studies in the Program Project and for laboratories world-wide that are interested in initiating basic or clinical studies of neuropsychiatric lupus. The Core will also produce decoy antigens once a lead candidate is identified. The studies enabled by these antibodies will hasten clinical strategies for neuroprotection in patients with lupus.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI073693-11A1
Application #
10024599
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2008-08-01
Project End
2025-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
11
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Feinstein Institute for Medical Research
Department
Type
DUNS #
110565913
City
Manhasset
State
NY
Country
United States
Zip Code
11030
Suurmond, Jolien; Atisha-Fregoso, Yemil; Marasco, Emiliano et al. (2018) Loss of an IgG plasma cell checkpoint in patients with lupus. J Allergy Clin Immunol :
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Honig, Gerard; Mader, Simone; Chen, Huiyi et al. (2016) Blood-Brain Barrier Deterioration and Hippocampal Gene Expression in Polymicrobial Sepsis: An Evaluation of Endothelial MyD88 and the Vagus Nerve. PLoS One 11:e0144215
Malkiel, Susan; Jeganathan, Venkatesh; Wolfson, Stacey et al. (2016) Checkpoints for Autoreactive B Cells in the Peripheral Blood of Lupus Patients Assessed by Flow Cytometry. Arthritis Rheumatol 68:2210-20

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