Background/Purpose: T and B cells come together in ectopic lymphoid aggregates in myositis, suggesting that local T:B cell interactions could play a role in disease.  T follicular helper cells are increased in circulation in patients with active myositis.  We studied circulating Tfh cells from myositis patients using single-cell RNA-sequencing and examined the proximity of Tfh cells to B cells in patient biopsies.

Methods: Tfh cells [CD3⁺CXCR5⁺PD-1⁺CXCR3^neg and CD3⁺CXCR5⁺PD-1⁺CXCR3^pos] cells were sorted from peripheral blood and subsets were identified by chemokine markers to designate Tfh1 and Tfh2/17 cell subsets.  RNA sequencing was performed on individual cells of (3 controls and 3 myositis patients) using Fluidigm C1 HT platform, and data were analyzed using a pseudo-temporal ordering using Monocle.  Biopsies were stained using the OPAL standardized sequential immunofluorescence method for PD-1, CXCR5, CD19, and CD4 in human muscle, and machine learning was used to map proximity of B cells to all T-cells compared with Tfh cells.

Results: We found various subsets within the Tfh pool, corresponding to Tfh1 and Tfh2/17 cells and some cells that looked to be transitioning between states.  Tfh2/17 were enriched in myositis patients vs. controls.  The Tfh2/17 cells demonstrated a type I interferon signature, while the Tfh1 cells had a type II interferon and proteasome signature.  In tissue, we demonstrate Tfh cells in close proximity to B cells in lymphoid aggregates.

Conclusion: Tfh cells are present in myositis biopsies juxtaposed to B cells, suggesting productive T:B interactions in the tissue.  Tfh subsets in blood from patients demonstrate distinct pathological signatures when compared to controls.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/interferon-pathway-activation-in-t-follicular-helper-tfh-cell-subsets-in-human-myositis/