RT Journal Article
SR Electronic
T1 Immune gene expression and functional networks in distinct lupus nephritis classes
JF Lupus Science & Medicine
JO Lupus Sci Med
FD Lupus Foundation of America
SP e000615
DO 10.1136/lupus-2021-000615
VO 9
IS 1
A1 Alyssa C Gilmore
A1 Hannah R Wilson
A1 Thomas D Cairns
A1 Marina Botto
A1 Liz Lightstone
A1 Ian N Bruce
A1 Herbert Terence Cook
A1 Matthew Caleb Pickering
A1 ,
YR 2022
UL http://lupus.bmj.com/content/9/1/e000615.abstract
AB Objective To explore the utility of the NanoString platform in elucidating kidney immune transcripts for class III, IV and V lupus nephritis (LN) using a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) kidney biopsy tissue.Methods Immune gene transcript analysis was performed using the NanoString nCounter platform on RNA from LN (n=55), thin basement membrane (TBM) disease (n=14) and membranous nephropathy (MN) (n=9) FFPE kidney biopsy tissue. LN samples consisted of single class III (n=11), IV (n=23) and V (n=21) biopsies with no mixed lesions. Differential gene expression was performed with NanoString nSolver, with visualisations of volcano plots and heatmaps generated in R. Significant transcripts were interrogated to identify functional networks using STRING and Gene ontogeny terms.Results In comparison to TBM, we identified 52 significantly differentially expressed genes common to all three LN classes. Pathway analysis showed enrichment for type I interferon (IFN) signalling, complement and MHC II pathways, with most showing the highest expression in class IV LN. Our class IV LN biopsies also showed significant upregulation of NF-κB signalling and immunological enrichment in comparison to class V LN biopsies. Transcripts from the type I IFN pathway distinguished class V LN from MN.Conclusion Our whole kidney section transcriptomic analysis provided insights into the molecular profile of class III, IV and V LN. The data highlighted important pathways common to all three classes and pathways enriched in our class IV LN biopsies. The ability to reveal molecular pathways in LN using FFPE whole biopsy sections could have clinical utility in treatment selection for LN.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. Data are provided in the supplemental excel file. Raw data files are available on request.