Molecular profiling of kidney compartments from serial biopsies differentiate treatment responders from non-responders in lupus nephritis.

Autor:	Parikh SV; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA. Electronic address: Samir.parikh@osumc.edu., Malvar A; Nephrology Unit, Hospital Fernandez, Buenos Aires, Argentina., Song H; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Shapiro J; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Mejia-Vilet JM; Department of Nephrology and Mineral Metabolism, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico; Department of Pathology, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico., Ayoub I; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Almaani S; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Madhavan S; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Alberton V; Department of Pathology, Hospital Fernandez, Buenos Aires, Argentina., Besso C; Department of Pathology, Hospital Fernandez, Buenos Aires, Argentina., Lococo B; Nephrology Unit, Hospital Fernandez, Buenos Aires, Argentina., Satoskar A; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Zhang J; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Yu L; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Fadda P; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Eadon M; Department of Medicine, Indiana University, Indianapolis, Indiana, USA., Birmingham D; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Ganesan LP; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Jarjour W; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Rovin BH; Division of Nephrology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Jazyk:	angličtina
Zdroj:	Kidney international [Kidney Int] 2022 Oct; Vol. 102 (4), pp. 845-865. Date of Electronic Publication: 2022 Jul 02.
DOI:	10.1016/j.kint.2022.05.033
Abstrakt:	The immune pathways that define treatment response and non-response in lupus nephritis (LN) are unknown. To characterize these intra-kidney pathways, transcriptomic analysis was done on protocol kidney biopsies obtained at flare (initial biopsy (Bx1)) and after treatment (second biopsy (Bx2)) in 58 patients with LN. Glomeruli and tubulointerstitial compartments were isolated using laser microdissection. RNA was extracted and analyzed by nanostring technology with transcript expression from clinically complete responders, partial responders and non-responders compared at Bx1 and Bx2 and to the healthy controls. Top transcripts that differentiate clinically complete responders from non-responders were validated at the protein level by confocal microscopy and urine ELISA. At Bx1, cluster analysis determined that glomerular integrin, neutrophil, chemokines/cytokines and tubulointerstitial chemokines, T cell and leukocyte adhesion genes were able to differentiate non-responders from clinically complete responders. At Bx2, glomerular monocyte, extracellular matrix, and interferon, and tubulointerstitial interferon, complement, and T cell transcripts differentiated non-responders from clinically complete responders. Protein analysis identified several protein products of overexpressed glomerular and tubulointerstitial transcripts at LN flare, recapitulating top transcript findings. Urine complement component 5a and fibronectin-1 protein levels reflected complement and fibronectin expression at flare and after treatment. Thus, transcript analysis of serial LN kidney biopsies demonstrated how gene expression in the kidney changes with clinically successful and unsuccessful therapy. Hence, these insights into the molecular landscape of response and non-response may help align LN management with the pathogenesis of kidney injury. (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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