1109 Visualizing in situ immune pathogenic mechanisms in human lupus nephritis. (14th December 2022)

• Record Type: Journal Article
• Authors: Clark, Marcus; Durkee, Madeleine; Abraham, Rebecca; Casella, Gabriel; Ai, Junting; Ghosh, Deepjyoti; Cao, Thao; Giger, Maryellen
• Is Part Of: Lupus science & medicine. Volume 9(2022)Supplement 3
• Page Start: A75
• Page End: A75
• Publication Date: 2022-12-14
• Subjects: Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1136/lupus-2022-lupus21century.74
• Languages: English
• ISSNs: 2398-8851

Abstract

Abstract : For over 50 years, systemic lupus erythematosus (SLE) has been thought to result from a break in systemic tolerance and production of pathogenic autoreactive antibodies. In the kidney, the manifestation of systemic autoimmunity is glomerulonephritis (GN). However, tubulointerstitial inflammation (TII)—and not GN—predicts progression to end stage renal disease (ESRD). Lupus TII is associated with a local immune response very different than the inflammation observed in glomeruli. These observations indicate that in situ immunity is a central pathogenic mechanism of lupus nephritis. Recently, we developed computational pipelines by training and implementing several deep learning models to identify cells and cellular spatial relationships in biopsies from lupus nephritis patients. When applied to confocal micrographs of renal tissue, this analytic approach revealed discrete in situ inflammatory states in lupus nephritis which differed in cellular constituency, spatial architecture and prognosis. These observations demonstrate the utility of studying in situ immunity to both identify prognostic groups and therapeutic targets. In follow up studies, we are using high dimensional confocal microscopy to capture the full complexity of lupus nephritis in situ immunity innate and adaptive immunity in order to identify those immunological pathways that lead to fibrosis and renal failure. Funded by grants from the NIH Autoimmunity Centers of Excellence (U19 AI082724) and Alliance for Lupus Research