Spatial Molecular Profiling of the Kidney of Children with Lupus Nephritis

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B574
Abstract ID: 7340

Presenting Author:
Juan F Rodriguez-Alcazar , Postdoctoral Associate at Weill Cornell Med.

Abstract:

Childhood-onset lupus nephritis (cLN) affects 80% of pediatric systemic lupus erythematosus patients. Classified based on histological renal features, cLN is treated with immunosuppressive agents that trigger side effects. Despite the need for targeted therapies, little is known on the molecular pathways causing cLN and their variability across patients. We employ spatial transcriptomics and proteomics approaches to profile kidney biopsies of cLN patients and define cellular and molecular endotypes across clinical traits. We found that distinct spatial organization of the renal immune compartment classified cLN biopsies according to histological classification. Myeloid cells with phagocytic and highly inflammatory transcriptional programs, including the expression of S100A9, infiltrate glomeruli of proliferative cLN. A subset of these patients also presents glomerular inflammasome-competent myeloid cells expressing IL-1β. Tubulointerstitial and periglomerular immune hubs characterize a subgroup of membranous and mixed cLN. Immune hubs’ cell composition varies across patients and tissue lesions and can be skewed towards specific lymphoid populations, including T, B, or plasma cells with different isotype specificity. Our results highlight the importance of understanding the spatial organization and heterogeneity of the renal immune compartment in cLN. The prognostic value of these findings and their relevance to target disease is being currently explored.