Background/Purpose: In recent work, we showed that a single measurement of several gene signatures in whole blood was associated with levels of disease activity at that time and in the next year.  In this study, we assessed the stability of these gene signatures over time, and whether changes in expression coincide with changes in disease activity.

Methods: Blood was collected at clinic visits from 298 members of a well-characterized SLE cohort (SPARE). 82 patients contributed one visit, 194 patients contributed 2 visits, 22 patients contributed 3 or more visits.  The interval between visits was approximately 28 to 135 days.  Levels of the BAFF gene transcript, plasma cell signature, Interferon (IFN)-α signature and the  Low Density Granulocytes (LDG)-associated Neutrophil gene signature were assessed in PAXgene-preserved peripheral blood by global microarray and qPCR. For multi-gene signatures, the geometric mean was calculated. The stability of repeated measures of gene expression was quantified using intra-class correlation coefficients (ICC).  To provide a frame of reference we also computed the ICC for systolic blood pressure and weight.  SLE disease activity was measured using the Physicians Global Assessment (PGA) and the SELENA-SLEDAI index and its components.The associations between changes in gene expression and changes in disease activity between two visits from the same person were assessed using linear regression models.

Results:  Table 1 shows the intraclass correlation coefficients for repeated measures of the gene signatures and also, to provide reference values, for systolic blood pressure and weight. It can be seen that the gene expression markers show more within-person stability than systolic blood pressure. The IFN-α signature exhibited the most stability.  Table 2 shows the association between changes in gene signature markers and changes in disease activity indices, adjusting for change in prednisone dose.  Few strong associations were observed.  A one standard deviation (SD) increase in expression of the plasma cell signature was associated with a 0.57 increase in SLEDAI values.

Conclusion:  The gene signatures that we studied are relatively stable within patients over time.  Although previous work has shown them related to disease activity, within a patient there was not a strong association between changes in gene expression and changes in disease activity.  This suggests that these gene signatures may not be dynamic indicators of disease activity under current standard of care therapy, but more likely to be indicators of subsets of patients with different underlying disease processes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-between-changes-in-expression-of-gene-signatures-and-disease-activity-among-patients-with-systemic-lupus-erythematosus/