By combining immune monitoring on multiple platforms in a single center, the Human Immune Monitoring Center (HIMC, ACE Core B) has created an ideal environment for standardization, technology development, and data mining related to immune monitoring. Over the last few years, we have built an array of high-throughput and high-content assays that have proven useful for a variety of immunological studies in autoimmunity. In our first Specific Aim, we propose to offer a battery of standardized assays in support of the Principal Project, Collaborative Project, and Pilot Project, including: (i.) a 51-plex Luminex assay for serum cytokines, and development of SLE-specific chemokine assays;(ii.) immunophenotyping;phosphor-flow, and intracellular cytokine staining by mass cytometry (CyTOF) using up to 40 simultaneous antibodies; (iii.) conventional phospho-flow using a panel of cytokine stimuli and pSTAT-1;3, and 5 readouts on 4 major cell types;(iv.) whole-genome gene expression microarrays;and (v.) FACS sorting of plasmablasts. In our second Specific Aim, we will develop enhancements to the above assays, including for example, enrichment techniques for intracellular cytokine staining, cell-surface barcoding for CyTOF, and optimized stimulation/fixation/freezing protocols for on-site sample handling for functional assays. Finally, in our third Specific Aim, we will further develop our online relational database, Stanford Data Miner (SDM) to be compatible with these assays, and to allow integration of data across assays and with relevant clinical variables. We also plan to add additional machine learning tools to SDM to allow efficient mining of complex data sets. HIMC (ACE Core B) is already supporting current ACE trials ASC01 and APA01. The long term goal of ACE Core B is to develop and disseminate new multiplexed assay methodology and Standard Operating Procedures, and to serve the overall ACE mission by participating in the ACE Shared Research Agenda.

Public Health Relevance

The HIMC core will facilitate the generation of high-content, standardized immunological data that can be mined across projects for new metrics of immune activity in autoimmune diseases, and potential biomarkers for diagnosis, disease activity, and response to therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI110491-01
Application #
8732979
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
City
Stanford
State
CA
Country
United States
Zip Code
94304
Bongen, Erika; Vallania, Francesco; Utz, Paul J et al. (2018) KLRD1-expressing natural killer cells predict influenza susceptibility. Genome Med 10:45
Elliott, Serra E; Kongpachith, Sarah; Lingampalli, Nithya et al. (2018) Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis. Arthritis Rheumatol 70:1946-1958
Cheung, Peggie; Vallania, Francesco; Warsinske, Hayley C et al. (2018) Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell 173:1385-1397.e14
Rosenberg, Jacob M; Maccari, Maria E; Barzaghi, Federica et al. (2018) Neutralizing Anti-Cytokine Autoantibodies Against Interferon-? in Immunodysregulation Polyendocrinopathy Enteropathy X-Linked. Front Immunol 9:544
Lu, Daniel R; McDavid, Andrew N; Kongpachith, Sarah et al. (2018) T Cell-Dependent Affinity Maturation and Innate Immune Pathways Differentially Drive Autoreactive B Cell Responses in Rheumatoid Arthritis. Arthritis Rheumatol 70:1732-1744
Rizzi, Giovanni; Lee, Jung-Rok; Dahl, Christina et al. (2017) Simultaneous Profiling of DNA Mutation and Methylation by Melting Analysis Using Magnetoresistive Biosensor Array. ACS Nano 11:8864-8870
Haddon, D James; Wand, Hannah E; Jarrell, Justin A et al. (2017) Proteomic Analysis of Sera from Individuals with Diffuse Cutaneous Systemic Sclerosis Reveals a Multianalyte Signature Associated with Clinical Improvement during Imatinib Mesylate Treatment. J Rheumatol 44:631-638
Degn, Søren E; van der Poel, Cees E; Firl, Daniel J et al. (2017) Clonal Evolution of Autoreactive Germinal Centers. Cell 170:913-926.e19
de Bourcy, Charles F A; Dekker, Cornelia L; Davis, Mark M et al. (2017) Dynamics of the human antibody repertoire after B cell depletion in systemic sclerosis. Sci Immunol 2:
Perkins, Tiffany; Rosenberg, Jacob M; Le Coz, Carole et al. (2017) Smith-Magenis Syndrome Patients Often Display Antibody Deficiency but Not Other Immune Pathologies. J Allergy Clin Immunol Pract 5:1344-1350.e3

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