The Molecular Phenotype of Lupus Nephritis Histological Lesions

Lupus nephritis (LN) is characterized by immune-complex deposition in kidney glomeruli and has been classified according to histological features, but has not been characterized on a molecular level. This study aimed to characterize the relationship between histological and molecular phenotypes in LN. Renal compartmental mRNA expression was measured in 54 kidney biopsy specimens from patients with LN and correlated to histological phenotypes. The top identified transcripts were compared to a separate longitudinal cohort of 36 patients with paired kidney biopsies obtained at the time of flare and at follow up. Unsupervised clustering based on mRNA abundance resulted in clear separation by renal compartment, but did not demonstrate a relationship with LN class based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, or the NIH activity and chronicity indices. A strong interferon gene signature was observed in both cohorts. FN1, SPP1, and LGALS-3 correlated with disease activity in both cohorts. The relationship between mRNA expression and ISN/RPS classification is modest. However, correlation of mRNA expression with individual histologic lesions identifies transcripts that change with resolution of disease flare, and provide insights into the molecular pathways potentially responsible for pathologic kidney lesions. Combining molecular and pathologic kidney biopsy phenotype may hold promise to better classify disease and identify actionable treatment targets. Kidney biopsy material was obtained from 54 patients undergoing a for-cause kidney biopsy at the Toronto General Hospital from January 2007 to December 2012. After written informed consent, a section of the clinical biopsy core was stored in RNA-later (Life Technologies, Carlsbad CA) at 4°C. After it was determined that this tissue was not required for clinical diagnosis, and the patient had agreed to banking the tissue, these cores were available for research per the University Health Network institutional protocol. Please contact Dr. Reich ([e-mail]) for additional (clinical) information.