The branch is focusing on identifying the role of aberrant neutrophils and neutrophil extracellular traps in the development of autoimmune responses and end-organ damage in systemic diseases including lupus (SLE), rheumatoid arthritis (RA) and systemic vasculitides (AAV). During this year, our group has identified specific components of NETs that may be involved in inducing interferogenic responses in SLE. we are also studying how lupus neutrophils modulate T cell function and mechanisms of oxidant production by neutrophils that may promote immune-mediated damage in lupus and other diseases. Our work is also examining neutrophil/synovial fibroblasts interactions in the RA synovium and the role this play in triggering abnormal innate and adaptive immunity in this disease. Lupus patients have evidence of aberrant HDL, which is highly oxidized and displays abnormal function, as measured by reverse cholesterol transport. We have studied during this year how this HDL may modify myeloid cell function and promote inflammation leading to premature vascular disease. Following a bench to bedside approach we are actively studying a well-characterized cardiovascular lupus cohort which is being followed prospectively for identification of novel biomarkers that predict progression of vascular inflammation, endothelial dysfunction and premature vascular events. We are using sophisticated imaging and functional vascular assays to quantify these abnormalities in lupus patients. We have an ongoing clinical trial to assess the role of PPAR-gamma agonists in modulating vascular function and disease activity in lupus patients, at the NIH Clinical Center. In collaboration with other investigators at NIAMS, we are investigating how JAK inhibitors may modulate autoimmunity and vascular damage in lupus using murine systems in vivo and human systems in vitro. Finally, in collaboration with Dr. Peter Grayson, we are focusing on better understanding how medications that are known to induce autoimmunity modulate immunogenicity of neutrophils as a mechanism leading to immune dysregulation. This applies to diseases like ANCA-vasculitis and lupus.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Arthritis, Musculoskeletal, Skin Dis
Zip Code
Liu, Yudong; Seto, Nickie L; Carmona-Rivera, Carmelo et al. (2018) Accelerated model of lupus autoimmunity and vasculopathy driven by toll-like receptor 7/9 imbalance. Lupus Sci Med 5:e000259
Carlucci, Philip M; Purmalek, Monica M; Dey, Amit K et al. (2018) Neutrophil subsets and their gene signature associate with vascular inflammation and coronary atherosclerosis in lupus. JCI Insight 3:
Irizarry-Caro, Jorge A; Carmona-Rivera, Carmelo; Schwartz, Daniella M et al. (2018) Brief Report: Drugs Implicated in Systemic Autoimmunity Modulate Neutrophil Extracellular Trap Formation. Arthritis Rheumatol 70:468-474
Gupta, Sarthak; Chan, Diana W; Zaal, Kristien J et al. (2018) A High-Throughput Real-Time Imaging Technique To Quantify NETosis and Distinguish Mechanisms of Cell Death in Human Neutrophils. J Immunol 200:869-879
Barrera-Vargas, Ana; Gómez-Martín, Diana; Carmona-Rivera, Carmelo et al. (2018) Differential ubiquitination in NETs regulates macrophage responses in systemic lupus erythematosus. Ann Rheum Dis 77:944-950
Liu, Yudong; Carmona-Rivera, Carmelo; Moore, Erica et al. (2018) Myeloid-Specific Deletion of Peptidylarginine Deiminase 4 Mitigates Atherosclerosis. Front Immunol 9:1680
Demoruelle, M Kristen; Bowers, Emily; Lahey, Lauren J et al. (2018) Antibody Responses to Citrullinated and Noncitrullinated Antigens in the Sputum of Subjects With Rheumatoid Arthritis and Subjects at Risk for Development of Rheumatoid Arthritis. Arthritis Rheumatol 70:516-527
Carmona-Rivera, Carmelo; Bicker, Kevin L; Thompson, Paul R et al. (2018) Response to comment on ""Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis"". Sci Immunol 3:
Liu, Yudong; Kaplan, Mariana J (2018) Cardiovascular disease in systemic lupus erythematosus: an update. Curr Opin Rheumatol 30:441-448
Grayson, Peter C; Alehashemi, Sara; Bagheri, Armin A et al. (2018) 18 F-Fluorodeoxyglucose-Positron Emission Tomography As an Imaging Biomarker in a Prospective, Longitudinal Cohort of Patients With Large Vessel Vasculitis. Arthritis Rheumatol 70:439-449

Showing the most recent 10 out of 62 publications