Article Text

  1. Z Jin1,
  2. MA Jensen1,
  3. JM Dorschner1,
  4. DM Vsetecka1,
  5. S Amin1,
  6. A Makol1,
  7. F Ernste1,
  8. T Osborn1,
  9. K Moder1,
  10. V Chowdhary1,
  11. TB Niewold1,
  12. W Fan2
  1. 1Division of Rheumatology and Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States
  2. 2Department of Rheumatology, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China


Background Our previous studies have shown that different cell types from the same blood sample demonstrate diverse gene expression parameters. In follow up work, it seems that this diversity extends to cells of the same type from the same blood sample. In this study, we examine single cell gene expression in SLE patient monocytes and determine correlations with clinical features.

Methods CD14++CD16 classical monocytes (CLs) and CD14dimCD16+ non-classical monocytes (NCLs) from SLE patients were purified by magnetic separation. The Fluidigm single cell capture and pre-amplification system was used for single cell capture and target gene pre-amplification. Fluidigm Biomark system (Rt-PCR system) was used to quantify expression of 87 monocyte-related genes. IFN-induced genes in monocytes were identified by culturing monocytes isolated from whole blood of healthy controls with or without IFN-α. Genes significant up-regulated by IFN were identified as IFN-induced genes in current study. An individual cell IFN score was given based upon the sum of expression of IFN-induced genes.

Results Both CLs and NCLs demonstrated a wide range of expression of IFN-induced genes, and NCL monocytes had higher IFN scores than CL monocytes. Using unsupervised hierarchical clustering, we found four gene sets that clustered monocytes functionally. These included an IFN-induced gene set, two inflammatory gene sets, and one immunosuppressive gene set. Interestingly, we could define a large subset of NCL monocytes with upregulation of suppressive transcripts (including TGF-β and PDL1) and IFN-induced transcripts were also upregulated, while the two inflammatory gene sets were down-regulated. These cells were highly over-represented in a patient with inactive disease who was on immunosuppressants at the time of blood draw. The proportion of anti-inflammatory gene set expressing NCLs was inversely correlated with anti-dsDNA titers (rho=−0.77, p=0.0051) and positively correlated with C3 complement (rho=0.68, p=0.030) in the SLE patient group, suggesting that these cells are also associated with serological quiescence.

Conclusion Using single cell gene expression, we have identified a unique population of NCL monocytes in SLE patients with upregulation of a combination of anti-inflammatory and IFN-induced transcripts. These cells correspond with clinical and serological quiescence.

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