Systemic Autoimmunity

National Institute Of Arthritis And Musculoskeletal And Skin Diseases

Investigators

Linked publications & trials

Abstract

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), inflammatory myopathies and systemic vasculitides (AAV) as well as various autoinflammatory syndromes. During this year, our group has continue to focus on understanding modulation of innate immune pathways by altering immunometabolism. We also reported new advances on how NETs promote bone damage in rheumatoid arthritis, through a process that involves distinct post-translational modifications of NET autoantigens as well as a putative role in periodontitis. Studies have also focused on better understanding neutrophil heterogeneity in health and disease using single cell RNA sequencing analysis and Cite-Seq, comparing a variety of inflammatory diseases. The branch uses sophisticated gene expression approaches including RNA sequencing, ATAC sequencing and single cell RNA sequencing to better understand cellular heterogeneity in autoimmune diseases and the role of specific cell subsets in mediating pathogenesis. The branch is also exploring how sex differences modulate neutrophil biology using similar techniques. We continue to use sophisticated imaging and functional vascular assays to quantify blood vessel abnormalities in lupus patients and are engaged in various investigator-initiated clinical trials at the Clinical Center to try to modulate vascular dysfunction in lupus. In recent studies, we are expanding our expertise in neutrophil biology to understand how neutrophil dysregulation is implicated in the pathogenesis of COVID-19. We reported the results of a study that assess how modulation of the Syk pathway can improve neutrophil dysregulation and outcome sin severe COVID-19 through a collaboration with investigators at the NIH Clinical Center.