Association between changes in gene signatures expression and disease activity among patients with systemic lupus erythematosus
JournalBMC Medical Genomics
PublisherBioMed Central Ltd.
MetadataShow full item record
AbstractBackground: We assessed the stability of BAFF, interferon, plasma cell and LDG neutrophil gene expression signatures over time, and whether changes in expression coincided with changes in SLE disease activity. Methods: Two hundred forty-three patients with SLE were evaluated for disease activity, serological parameters and peripheral blood gene signatures in clinic visits (2 or more per patient) that occurred between 2009 and 2012. Levels of the BAFF gene transcript, plasma cell signature, Interferon (IFN) signature and the low density granulocytes (LDG)-associated neutrophil gene signature were assessed in PAX-gene-preserved peripheral blood by global microarray. The stability of repeated measures of gene expression was quantified using intra-class correlation coefficients. SLE disease activity was measured using the Physicians Global Assessment and the SELENA-SLEDAI index and its components. Using a mixed effects regression model we assessed: 1) the association between a patient's average gene signature expression over time and disease activity, and 2) the association between a patient's changes in gene expression over time and changes in disease activity. Results: Gene expression signatures showed more within-person stability than systolic blood pressure. The IFN signature exhibited the most stability. Patients with high levels of BAFF and IFN transcripts tended to have significantly higher levels of musculoskeletal disease, skin disease, anti-dsDNA, and erythrocyte sedimentation rate, and lower levels of complement. However, changes in BAFF or IFN gene signatures were not associated with changes in disease activity. Similar associations were seen between the LDG gene signature and disease activity. However, when LDG increased, complement tended to increase. Patients with high levels of plasma cell gene signature tended to have higher levels of anti-dsDNA and lower levels of complement. However, unlike the other gene signatures, changes in plasma cell gene signature significantly coincided with changes in anti-dsDNA and complement. Conclusions: The gene expression signatures were relatively stable within patients over time. BAFF and interferon gene expression were markers of patients with generally higher disease activity, but changes in these gene signatures did not coincide with changes in disease activity. Plasma Cell gene signature expression tracked with the traditional SLE serologic markers of anti-dsDNA and complement. Copyright 2019 The Author(s).
SponsorsThe Hopkins Lupus Cohort is supported by NIH (R01 AR043727 and R01 AR069572). Biogen provided funding for part of this study. Biogen reviewed the manuscript for editorial quality prior to submission, but was not involved in the study design, data collection, analysis, or interpretation of the data.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85059797507&doi=10.1186%2fs12920-018-0468-1&partnerID=40&md5=9bc9ea73edb068694d40fb8a5809ed81; http://hdl.handle.net/10713/8617