Summary

Juvenile dermatomyositis (JDM) is a rare autoimmune condition with insufficient biomarkers and treatments, in part, due to incomplete knowledge of the cell types mediating disease. We investigated immunophenotypes and cell-specific genes associated with disease activity using multiplexed RNA and protein single-cell sequencing applied to PBMCs from 4 treatment-naïve JDM (TN-JDM) subjects at baseline, 2, 4, and 6 months post-treatment and 4 subjects with inactive disease on treatment. Analysis of 55,564 cells revealed separate clustering of TN-JDM cells within monocyte, NK, CD8+ effector T and naïve B populations. The proportion of CD16+ monocytes was reduced in TN-JDM, and naïve B cells and CD4+ Tregs were expanded. Cell-type differential gene expression analysis and hierarchical clustering identified a pan-cell-type IFN gene signature over-expressed in TN-JDM in all cell types and correlated with disease activity most strongly in cytotoxic cell types. TN-JDM CD16+ monocytes expressed the highest IFN gene score and were highly skewed toward an inflammatory and antigen-presenting phenotype at both the transcriptomic and proteomic levels. A transitional B cell population with a distinct transcriptomic signature was expanded in TN-JDM and characterized by higher CD24 and CD5 proteins and less CD39, an immunoregulatory protein. This data provides new insights into JDM immune dysregulation at cellular resolution and serves as a novel resource for myositis investigators.

Overall design

This study includes single-cell RNA and ADT (protein) measurements of PBMCs from 4 treatment-naïve JDM (TN-JDM) subjects at baseline, 2, 4, and 6 months and 4 subjects with inactive disease. Samples were multiplexed across four 10X reactions. Provided in GEO are the filtered RNA and ADT matrices we used for clustering and differential gene expression analysis. We have also included a metadata file with cell annotations and file with UMAP coordinates to re-create our cell clusters.

Contributors

To be supplemented.

Contact

To be supplemented.