Background/Purpose: We assessed the stability of BAFF, interferon, plasma cell and LDG neutrophil gene expression signatures over time, and whether changes in gene expression coincided with changes in SLE disease activity.

Methods: 243 patients with SLE were evaluated for disease activity, serological parameters and peripheral blood gene signatures in clinic visits that occurred between 2009 and 2012. 143 SLE patients contributed two visits, 40 patients contributed three visits and 60 patients contributed four or more visits. 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. For multi-gene signatures, the geometric mean of component expression was calculated. The stability of repeated measures of gene expression was quantified using intra-class correlation coefficients (ICC). SLE disease activity was measured using the Physicians Global Assessment (PGA) 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 ESR, and lower levels of complement. However, changes in BAFF or IFN gene signatures were not associated with changes in disease activity. The same 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.

Conclusion: The gene expression signatures were relatively stable within patients over time. BAFF and IFN 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. The plasma cell gene signature expression tracked with the traditional SLE serologic markers of anti-dsDNA and complement.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-changes-in-gene-signature-expression-and-disease-activity-in-systemic-lupus-erythematosus/