Purpose We sought to identify distinct blood transcriptomic signatures of NPSLE patients that could serve as potential biomarkers and therapeutic targets.
Methods NPSLE was defined as patients with primary neuropsychiatric events (attributed to SLE) using a combination of multidisciplinary physician judgment with attribution models. Patients without neuropsychiatric events or secondary NPSLE (neuropsychiatric manifestations not attributed to SLE) were classified as non-NPSLE. Diagnosis of SLE was established by the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 criteria. RNA-sequencing was performed in peripheral blood from 172 individuals (54 NPSLE, 94 non-NPSLE and 24 healthy controls). Relative expression levels of transcripts and differentially expressed genes (DEGs) (FC >1.5, FDR <0.2) were calculated. Gene set enrichment analysis (GSEA; Preranked) and Gene ontology (GO; gprofiler) analyses were performed in RNA datasets.
Results Comparison of NPSLE with healthy controls revealed 103 DEGs mainly involved in inflammatory pathways (leukocyte cell-cell adhesion, regulation of leukocyte proliferation, neutrophil aggregation, complement and coagulation cascades, Toll-like receptor binding, NF-kappa B signaling pathway) suggesting that systemic inflammation is a key component in NPSLE pathogenesis. Comparison of NPSLE with non-NPSLE patients by GSEA analysis (FDR<0.25) revealed angiogenesis (FGFR1, LPL, PGLYRP1), complement (C3, ITGAM, CASP7), coagulation (VWF, ADAM9, CAPN2) G2M checkpoint (CHEK1, MKI67, CDKN3), MYC targets (XRCC6, PCNA, ILF2), E2F targets (CDK1, CKS1B, SMC3), estrogen response (MYB, CKB, SLC1A4), neutrophil degranulation (TNFAIP6, MMP8, LCN2) and PPAR signaling pathway (DBI, LPL, FABP5) being significantly enriched in NPSLE.
Conclusions NPSLE patients exhibit distinct transcriptomic signature compared to SLE patients without NP events. These data could facilitate the development of novel biomarkers and therapeutic targets.
Acknowledgments The European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no.742390); and the SYSCID (A Systems Medicine Approach to Chronic Inflammatory Diseases) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no.733100).
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.