Th102 - Single-cell Analysis of Monocyte Subpopulations in Untreated Large Vessel Vasculitis

Roman Sankowski – Institute of Neuropathology – University of Freiburg, Germany; Nils Venhoff – Rheumatology and Clinical Immunology – University of Freiburg, Germany; Reinhard Voll – Rheumatology and Clinical Immunology – University of Freiburg, Germany

Abstract Text: Giant cell arteritis (GCA) is a large vessel vasculitis of unknown cause, affecting only individuals older than 50 years of age. Autoantibodies are not detectable and specific lab markers are lacking. The disease is characterized by an acute inflammation with unspecific upregulation of acute phase reactants, which are mainly produced by innate immune cells. Affected arteries are infiltrated by monocytes and macrophages, which digest the basement membrane and, thus, allow infiltration of CD4+ T cells and formation of granulomatous lesions. In essence, GCA is characterized by a strong pathophysiological role of the innate immune system. However, whether there are disease-causing defects in cells of the innate immune system or specific disease-causing cell populations is currently unknown.
Here, we performed single-cell RNA sequencing of circulating monocytes from the peripheral blood of patients with active untreated GCA and healthy age-match controls. To preserve the information of potentially underrepresented monocyte populations, e.g. low frequent non-classical monocytes, we captured the individual transcriptomes from equivalent cell numbers of each monocyte subset. Using this technique, we identified a disease-specific monocyte population within the classical monocyte compartment that is not detectable in healthy individuals of the same age. This monocyte cluster disappears in GCA patients 3 months after start of therapy indicating that monocytes with this transcriptome are involved in the initiation or the very early phases of the disease, making this population a candidate for new therapies and a possible diagnostic tool.