Abstract: TH-PO053

Transcriptional Profile Distinguishes Two Groups of ANCA Vasculitis Patients Independent of Serotype

Session Information

Category: Glomerular

  • 1001 Glomerular: Basic/Experimental Immunology and Inflammation

Authors

  • Jones, Britta E., UNC Chapel Hill, Chapel Hill, North Carolina, United States
  • Starmer, Joshua, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Poulton, Caroline J., UNC Kidney Center, Chapel Hill, North Carolina, United States
  • Jennette, J. Charles, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
  • Falk, Ronald J., UNC Chapel Hill, Chapel Hill, North Carolina, United States
  • Ciavatta, Dominic J., University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States
Background

Increased expression of ANCA autoantigen genes myeloperoxidase (MPO) and proteinase 3 (PRTN3) has been observed in several cell types, but global transcriptional changes are less well defined in ANCA vasculitis patients.

Methods

We isolated neutrophils, CD14+ monocytes and CD4-enriched cells, from 30 healthy controls and 75 patients during active disease or remission, including 25 longitudinal patient pairs. Expression of MPO and PRTN3 in these purified cell populations was determined by quantitative real-time PCR. RNA-seq was performed on the CD4-enriched cell population from 12 active-remission pairs, 7 MPO-ANCA and 5 PR3-ANCA, to identify differentially expressed genes (DEGs) between active disease and remission.

Results

Expression of the autoantigen genes was elevated in patients with active disease compared to healthy controls in all three cell populations. A non-significant fold change in expression was seen in monocytes while the mean fold-change in expression for MPO and PRTN3, respectively, was 2.6; 3.6 in neutrophils and 7; 15.8 in the CD4-enriched cell population. Analysis of autoantigen gene expression in the CD4-enriched cell fraction and neutrophils in active-remission pairs revealed two groups of patients: patients with decreased expression from active disease to remission and those in which MPO and PRTN3 mRNA did not change. RNA-seq of active-remission pairs detected three DEG in patients where MPO and PRTN3 expression did not change. In patients who decreased autoantigen expression from active disease to remission, 468 significantly DEGs were detected including granulocyte genes [Figure 1].

Conclusion

The transcriptional profile that divides ANCA vasculitis patients into two categories suggests a molecular signature can distinguish disease status.

Summary of RNAseq analysis on active remission pairs. Red dots indicate differentially expressed genes.

Funding

  • NIDDK Support