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Molecular characterization of kidney compartments from serial biopsies to differentiate treatment responders from non-responders in lupus nephritis

ABSTRACT: The immune pathways that define treatment response and non-response in lupus nephritis (LN) are unknown. To characterize these intra-renal pathways, transcriptomic analysis of protocol kidney biopsies was done. Kidney biopsies were done at flare (Bx1) and after treatment (Bx2) in 58 LN patients and healthy controls (HC). Glomeruli and tubulointerstitium (TI) were isolated using laser microdissection. RNA was extracted and analyzed by nanostring. Transcript expression from clinical complete (CR), partial (PR) and non-responders (NR) were compared at Bx1 and Bx2 and to HC. Top transcripts that differentiate CR from NR were identified. Confocal microscopy and urine ELISA was done to evaluate the protein expression of top transcripts. At Bx1 cluster analysis determined that glomerular integrin, neutrophil, and chemokine/cytokine, and TI chemokine, T cell and leukocyte adhesion genes differentiated NR from CR. At Bx2, glomerular monocyte, extracellular matrix, and interferon, and TI interferon, complement, and T cell transcripts differentiated NR from CR. Protein analysis recapitulated top transcript findings. Urine C5a and FN1 differentiated NR from CR after treatment. Transcript analysis of serial kidney biopsies taken during the treatment of LN demonstrated how gene expression in the kidney changes with clinically successful and unsuccessful therapy. These insights into the molecular landscape of response and non-response may help better align LN management with the pathogenesis of kidney injury.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200306 | GEO | 2022/07/15

REPOSITORIES: GEO

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