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
Lofgren, Shane; Hinchcliff, Monique; Carns, Mary et al. (2016) Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity. JCI Insight 1:e89073
Robinson, William H; Mao, Rong (2016) Biomarkers to guide clinical therapeutics in rheumatology? Curr Opin Rheumatol 28:168-75
Slight-Webb, Samantha; Lu, Rufei; Ritterhouse, Lauren L et al. (2016) Autoantibody-Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity. Arthritis Rheumatol 68:2492-502
Lee, Jung-Rok; Haddon, D James; Wand, Hannah E et al. (2016) Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus. Sci Rep 6:27623
Lee, Jung-Rok; Haddon, D James; Gupta, Nidhi et al. (2016) High-Resolution Analysis of Antibodies to Post-Translational Modifications Using Peptide Nanosensor Microarrays. ACS Nano 10:10652-10660
Lee, Jung-Rok; Bechstein, Daniel J B; Ooi, Chin Chun et al. (2016) Magneto-nanosensor platform for probing low-affinity protein-protein interactions and identification of a low-affinity PD-L1/PD-L2 interaction. Nat Commun 7:12220
Rosenberg, Jacob M; Price, Jordan V; Barcenas-Morales, Gabriela et al. (2016) Protein microarrays identify disease-specific anti-cytokine autoantibody profiles in the landscape of immunodeficiency. J Allergy Clin Immunol 137:204-213.e3
Lee, Jung-Rok; Sato, Noriyuki; Bechstein, Daniel J B et al. (2016) Experimental and theoretical investigation of the precise transduction mechanism in giant magnetoresistive biosensors. Sci Rep 6:18692
Rosenberg, Jacob M; Utz, Paul J (2015) Protein microarrays: a new tool for the study of autoantibodies in immunodeficiency. Front Immunol 6:138
Chakravarty, Eliza F; Martyanov, Viktor; Fiorentino, David et al. (2015) Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis. Arthritis Res Ther 17:159

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